Icbs 2018 Program

7th Annual Conference
September 24-27, 2018

Vancouver, Canada
ICBS 2018
Scientific Program
Towards Translational Impact
www.chemical-biology.org
7th Annual Conference | September 24-27, 2018 | Vancouver, Canada
Acknowledgements
Towards Translational Impact

September 24th – 27th, 2018 | Vancouver, BC
Local Program and Organizing Committee

Tom Pfeifer, Centre for Drug Research and Development Roger Linington, Simon Fraser University
Michel Roberge, University of British Columbia Nicolette Honson, Centre for Drug Research and Development
ICBS Organizing Committee

Haian Fu, Chair, Emory University, USA Lixin Zhang, ECUST, China
Sally-Ann Poulsen, Griffith University, Australia Jonathan Baell, Monash University, Australia
Mahabir Gupta, University of Panama, Panama Junying Yuan, Harvard Medical School, USA
Masatoshi Hagiwara, Kyoto University, Japan Petr Bartunek, CZ-OPENSCREEN and Institute of Molecular
Jason Micklefield, The University of Manchester, UK Genetics, Czech Republic
Siddhartha Roy, Boss Institute, India
ICBS Young Chemical Biologist Award 2018 Selection Committee

Yimon Aye, Cornell University, USA Christian Ottmann, Technische Universiteit Eindhoven,
Ratmir Derda, University of Alberta, Canada Netherlands
Evripidis Gavathiotis, Albert Einstein College of Medicine, USA William Pomerantz, University of Minnesota, USA
Kenjiro Hanaoka, University of Tokyo, Japan Qi Zhang, Fudan University, China
Recording of sessions (oral or poster) by audio, video, or still photography is strictly prohibited except with the advance
permission of the author(s) and the conference organizers.
Material contained in abstracts and presentations should be treated as personal communication and cited as such only
with consent of the author(s).
2 www.chemical-biology.org
ICBS 2018
Table of Contents
Acknowledgements......................................................2 Thank you to our conference sponsors.......................16
ICBS Board of Directors...............................................4 Keynote Speakers......................................................17
About ICBS..................................................................4 Presentations.............................................................19
ICBS International Advisory Board................................5 Rising Stars................................................................48
Program at a Glance.....................................................6 Exhibitors...................................................................52
Welcome Letter............................................................9 Poster Presenters.......................................................53
Program.....................................................................10 Venue Map.................................................................55
Author Index
A G M T
Masahiko Ajiro......................... 32 Thota Ganesh.......................... 54 Dawei Ma................................ 39 Mirelle Takaki........................... 54
Rima Al-awar........................... 31 Thomas Garner....................... 53 Florian Mayerthaler.................. 34 Lily Takeuchi............................ 54
Matthew Alteen....................... 54 Chloe Gerak............................ 53 Guillaume Médard................... 54 Hong Yee Tan.......................... 53
Sebastian Andrei..................... 54 Paul Guyett.............................. 37 James Meinig.......................... 53 Masayasu Toyomoto................ 54
Albert A. Antolin....................... 25 Poncho Meisenheimer............. 46 Michihiko Tsushima.................. 53
Heather Arnaiz......................... 53 Jason Micklefield..................... 33
H
Doug Auld............................... 54 Cameron Murray...................... 54
V
Fred Haeckl............................. 53
Stephen J. Haggarty................ 36 David Vocadlo......................... 21
B N
Ting Han................................. 19
Anne Bang.............................. 37 Evan Haney............................. 54 Seyed Nasseri......................... 53
W
Jeremy M. Baskin.................... 29 Jason Hedges......................... 54 Ali Nejatie................................ 53
J.B. Brown.............................. 24 Stephanie Heinzlmeir............... 54 Sherry L Niessen..................... 42 Chu Wang............................... 49
Nicole Houszka....................... 53 Shaomeng Wang..................... 19
Amy Weeks............................. 54
C P
Julian Wilke............................. 53
I
Robert Campbell..................... 45 Andrew J. Phillips.................... 43 Michael Winzker...................... 53
Michelle Chang ....................... 33 Takayuki Ikeno......................... 53 Sally-Ann Poulsen.................... 27 Scott Wolkenberg.................... 30
Wansang Cho.......................... 53 Alena Istrate............................ 53 Polina Prokofeva...................... 54 Jeffrey Y.K. Wong.................... 53
Michael Cohen........................ 49 Andrey Ivanov.......................... 25 Christina Woo.......................... 48
Q
D J Y
Kun Qian................................. 54
Phillip Danby............................ 54 Namrata Jain........................... 54 Kenzo Yamatsugu................... 53
Francois Jean.......................... 54
R
Shireen Jozi............................. 54
E Z
Elena Reckzeh......................... 53
Joseph Egan........................... 53 Anna Rutkowska-Klute............ 54 Charlotte Zammit..................... 53
K
Syusuke Egoshi....................... 53 Katherine Ryan........................ 34 Cristina Zamora....................... 22
Akane Kawamura.................... 54 Andrew Zhang......................... 42
Jennifer Kohler ....................... 21 Jin Zhang................................ 45
F S
Milka Kostic............................. 27 Ji-Shen Zheng......................... 40
Victor Fadipe........................... 54 Casey Krusemark.................... 31 Koichi Sasaki........................... 54
Y. George Zheng..................... 43
Eric S. Fischer......................... 20 Karson Kump.......................... 53 Shinichi Sato........................... 40
Frederic Friscourt..................... 22 Saiko Shibata.......................... 53
Eline Sijbesma......................... 54
L
Ellen M. Sletten........................ 46
Nicole LeGrow......................... 53 Kimberly Snyder...................... 38
Jasmine Li-Brubacher.............. 53 Mathieu Soetens..................... 53
Dennis Liu............................... 53 Barbara Sohr........................... 53
Scott Lovell............................. 28
David Lupton........................... 39
www.chemical-biology.org 3
ICBS Board of Directors
Lixin Zhang Haian Fu Jonathan Baell

President (China) Chair of Board (USA) President Elect (Aus)
Rathnam Chaguturu Tom Pfeifer Masatoshi Hagiwara

Treasurer (USA) Secretary (Can) (Japan)
Zaneta Nikolovska-Coleska Siddhartha Roy

(USA) (India)
About ICBS
The International Chemical Biology Society (ICBS) is an independent, nonprofit organization dedicated to promoting
research and educational opportunities at the interface of chemistry and biology. ICBS provides an important international
forum that brings together cross-disciplinary scientists from academia, non profit organizations, government, and
industry to communicate new research and help translate the power of chemical biology to advance human health.
ICBS 2018
ICBS International Advisory Board
Stephen Benkovic Sir Philip Cohen Jian Ding

Penn State University of Dundee Shanghai Institute of Materia Medica
Chris Lipinski Ferid Murad Bernard Munos

Melior Discovery George Washington University InnoThink
Litao Zhang Stuart Schreiber Paul Workman

Bristol-Myers Squibb Harvard ICR-London
Tetsuo Nagano Leonard Zon Herbert Waldmann

University of Tokyo HHM/Harvard Max Planck Institute of Molecular Physiology
Junying Yuan
Harvard
Program at a Glance
PRECONFERENCE: MONDAY, SEPTEMBER 24, 2018
8:00AM – 6:00PM Meeting Registration Playhouse Lobby
8:30AM – 9:00AM Coffee Playhouse Lobby
9:00AM – 5:00PM Young Chemical Biologists’ Forum Orchestra Right & Left
9:00AM – 9:10AM Welcome Orchestra Right & Left
Expert-Led Forum
9:10AM – 9:40AM Chemistry for Biologists Jonathan Baell, Monash University, Australia
Assay Development and Screening Doug Auld, Novartis Institute for
9:10AM – 11:10AM 9:40AM – 10:10AM
Biomedical Research, USA
10:10AM – 10:40AM Structural Biology Scott Lovell, University of Kansas, USA
10:40AM – 11:10AM Insights for Chemical Biology in Industry Andrew Zhang, AstraZeneca, USA
11:10AM – 11:25AM Coffee Break Playhouse Lobby
11:25AM – 12:45PM Student-Led Forum, Presenters 1 through 5 Orchestra Right & Left
12:45 PM – 1:45PM Lunch on Your Own
1:45PM – 3:00PM Student-Led Forum, Presenters 6 through 10 Orchestra Right & Left
Tech Talks Orchestra Right & Left
Creating and Deploying Next Generation Informatics Solutions – What

3:00PM – 3:30PM 3:00PM – 3:15PM
We’ve Learned Along the Way Whitney Smith, Collaborative Drug Discovery, USA
3:15PM – 3:30PM Antibody-Drug Conjugates Graham Garnett, Zymeworks, Canada
3:30PM – 3:50PM Coffee Break and Exhibitor Viewing Salon A
3:50PM – 4:00 PM ICBS Conference Welcome Orchestra Right & Left
4:00PM – 4:05PM Keynote Introduction Orchestra Right & Left
Keynote – Craig M. Crews, Yale University, USA

4:05PM – 4:50PM PROTAC-mediated Protein Degradation: Making Problem Orchestra Right & Left
Proteins Go Away
ICBS Opening Reception and Young Chemical Biologists’ Social –
Shark Club, Library Room
5:00PM – 8:00PM Off-Site | Shark Club
Please join us for hors d’oeuvres and to network with your colleagues.
CASH BAR is available
ICBS 2018
CONFERENCE DAY 1: TUESDAY, SEPTEMBER 25, 2018

9:00AM – 9:15AM Welcome Orchestra Right & Left
Session I - Degradomics
9:15AM – 10:30PM Orchestra Right & Left
Chair: Shaomeng Wang
10:30AM – 10:50AM Coffee Break and Exhibitor Viewing Salon A
Session II – Glyco Chemical Biology

Chair: David Vocadlo
12:15PM – 1:15PM Lunch on Your Own and Exhibitor Viewing Salon A
Open Panel Discussion

Chair: Rathnam Chaguturu, iDDPartners, USA
1:15PM – 1:55PM Orchestra Right & Left
Academic/Industry Partnerships to Promote Drug Discovery Through
Chemical Biology
1:55PM – 2:10PM Conference Updates Orchestra Right & Left
Session III – Computational Chemical Biology

Chair: J.B. Brown
Session IV - Emerging and Other Topics

Chair: Sally-Ann Poulsen
Poster Session on Balcony Level: Odd Numbered Presentations
5:00PM – 7:00PM Please join us for hors d’oeuvres and to network with your colleagues. Balcony Level
CASH BAR is available.
CONFERENCE DAY 2: WEDNESDAY, SEPTEMBER 26, 2018

9:00AM – 9:05AM Conference Updates Orchestra Right & Left
Session V – The Chemical Biology – Medicinal Chemistry

9:05AM – 10:25AM Continuum Orchestra Right & Left
Chair: Yves Auberson
Session VI– Synthetic Biology

Chair: Jason Micklefield
12:15PM – 1:15PM Lunch on Your Own and Exhibitor Viewing

Session VII – iPSC Chemical Biology
Chair: Steve Haggarty

2:35PM – 3:10 PM ICBS Business Meeting Orchestra Right & Left
Rising Stars
Chair: Haian Fu
Poster Session on Balcony Level: Even Numbered Presentations
5:00PM – 7:00PM Please join us for hors d’oeuvres and to network with your colleagues. Balcony Level
CASH BAR is Available
CONFERENCE DAY 3: THURSDAY, SEPTEMBER 27, 2018

9:00AM – 09:05AM Conference Updates Orchestra Right & Left
Session VIII – Synthetic Chemistry

9:05AM – 10:25AM Orchestra Right & Left
Chair: David Lupton
10:45AM – 10:50AM Keynote Introduction Orchestra Right & Left
Keynote - Jörn Piel, ETH Zurich, Switzerland

10:50AM – 11:35AM Orchestra Right & Left
New Enzyme Tools From Uncharted Natural Product Space
Open Panel Session
Chair: Paul Clemons, Broad Institute, USA
Target Identification and Mechanism-of-Action Studies Using
Chemical Biology
Session IX – Chemical Proteomics for Drug Target Engagement

Chairs: Michael Finley and Andrew Zhang
Awards Presentation
Poster Awards sponsored by ChemBridge and Novartis
Travel Awards sponsored by Novartis, GlycoNet, STEMCELL
Technologies and Beckman Coulter
Session X– Biosensors and Imaging

Chair: Jin Zhang
4:50PM – 5:00PM Closing Remarks Orchestra Right & Left
ICBS 2018
Welcome Letter
Dear ICBS Members and Colleagues, We are particularly proud of this year’s pre-conference
Young Chemical Biologists’ Forum, a day organized for
We are delighted to welcome you to the Seventh Annual
and by young researchers and trainees. For anyone new
Conference of the International Chemical Biology Society
to the field, the day is intended to deepen their knowledge
(ICBS) in the beautiful city of Vancouver.
and expertise in different topics so as to enable innovative
Once again, this cross-disciplinary conference provides approaches to overcome the current and future challenges
an opportunity and forum to bring together international in chemical biology, resulting in mobilizing the next cohort
leaders, field drivers, rising stars, trainees and contributors of scientists. Thanks to the faculty and industry seminar
from across the global chemical biology community to presenters who volunteered to share their knowledge
share technological advances, exciting breakthroughs, with our trainees.
and new information. It also provides a forum for creating
Our thanks go to the members of the Organizing
new collaborations with colleagues from around the
Committees who have worked hard to shape the program
world, and to discuss the momentum of the field and our
and invite speakers whose work is relevant and germane
impact on society.
to our theme. We also wish to acknowledge Malachite
This year’s conference theme is Towards Translational Management Inc. who have kept us on a timeline to
Impact. Moving from the bench towards utility in the make sure this conference would happen, and provided
clinic, industry or environment; chemical biology has numerous helpful tips and advice along the way. As
emerged as a powerful approach to provide proof of always, special thanks go out to our Corporate Sponsors
concept in model systems. It allows us to understand and Exhibitors for their generous support and without
the relationship between target activity modulation by whom the conference would not be possible.
chemical compounds and phenotypic consequences,
Thanks to the Keynote speakers, other invited speakers,
thus enabling the full potential of our discoveries.
oral and poster presenters who together comprise a
Chemical biology plays a special role in this translation
program rich in content and variety.
by developing tools and methodologies to test and study
the impact of these discoveries. As we listen to the fine Enjoy your stay in Vancouver, a city unlike any other. A city
line up of oral presentations and posters at ICBS2018, with beautiful nature sceneries, a city with unique mix of
take a moment to rationalize the theories/hypotheses that cultures, excellent food and energetic life style. We hope
each presenter is bringing to the table, as this may be you will have wonderful time and we would like to invite
the knowledge that one day may impact your translational you to attend next year’s ICBS conference planned for
research. India in November, 2019!
As always both young and established scientists will Yours truly,
present at this meeting, providing a robust and interactive
Tom Pfeifer, PhD, Centre for Drug Research and Development,
platform for all to learn, discuss and share throughout the Vancouver, BC, Canada
course of the conference. The Rising Stars in Chemical
Zaneta Nikolovska-Coleska, MS, PhD, University of Michigan,
Biology Awards Session will feature up-and-coming Medical School, Ann Arbor, MI, USA
scientists in the field and will, as always, be a source of
ICBS2018 Co-Chairs
inspiration to all delegates. Overall, this conference will
enable the ICBS community to further disseminate its
scope and mission and to attract a growing number of
members.
Program
8:00AM – 6:00PM Meeting Registration
8:30AM – 9:00AM Coffee
9:00AM – 5:00PM Young Chemical Biologists’ Forum
9:00AM – 9:10AM Welcome
9:10AM – 11:10AM Expert-Led Forum
Chemistry for Biologists – Jonathan Baell, Monash University, Australia
9:10AM – 9:40AM
PAINS and Nuisance Compounds: Sorting the Wheat from the Chaff in Bioactive Compounds
Assay Development and Screening – Doug Auld, Novartis Institute for Biomedical Research, USA
9:40AM – 10:10AM
Considerations in the Design and Interpretation of Assays Applied to Drug Discovery
Structural Biology – Scott Lovell, University of Kansas, USA
10:10AM – 10:40AM
Gene to Structure: Utilizing X-Ray Crystallography to Support Chemical Biology
Insights for Chemical Biology in Industry – Andrew Zhang, AstraZeneca, USA
10:40AM – 11:10AM
Chemical Biology in Industry: Small Molecule Driven Target Deconvolution Strategies
11:10AM – 11:25AM Coffee Break
11:25AM – 12:45PM Student-Led Forum, Presenters 1 through 5
Kun Qian, Emory University, USA
11:25AM – 11:40AM
Chemical Probe Discovery to Interrogate YAP-TEAD Interaction in The Hippo Signaling Pathway
Eline Sijbesma, Eindhoven University of Technology, Netherlands
11:40AM – 11:55AM
Disulfide Trapping for the Identification of Selective PPI Stabilizers
Ali Nejatie, Simon Fraser University, Canada
11:55AM – 12:10PM
Synthesis of Biological Probes
Philip Danby, University of British Columbia, Canada
12:15AM – 12:30PM
Glycosyl vs Allylic Cations in Spontaneous and Enzymatic Hydrolysis
Michael Winzker, Max Planck Institute of Molecular Physiology, Germany
12:30PM – 12:45PM
Proteolysis Targeting Chimera (PROTAC) – A New Tool in Drug Discovery
12:45 PM – 1:45PM Lunch on Your Own
1:45PM – 3:00PM Student-Led Forum, Presenters 6 through 10
Sebastian Andrei, Eindhoven University of Technology, Netherlands
1:45PM – 2:00 PM
Rational Design of Semi-synthetic Natural Product 14-3-3 PPI Stabilizers
Karson Kump, University of Michigan, USA
2:00PM – 2:15 PM
Targeting Mcl-1 to Overcome Resistance in Solid Tumors
Oluwafemi Akintola, Simon Fraser University, Canada
2:15PM – 2:30 PM
Allylic Carbasugars as Substrates for Glycoside Hydrolases
Elena Reckzeh, Max Planck Institute of Molecular Physiology, Germany
2:30PM – 2:45 PM
Thermal Proteomic Profiling for Target Identification
Thomas Garner, Albert Einstein College of Medicine, USA
2:45PM – 3:00 PM
Allosteric Modulation and Therapeutic Inhibition of Pro-Apoptotic BAX
ICBS 2018

3:00PM – 3:30PM Tech Talks
Creating and Deploying Next Generation Informatics Solutions – What We’ve Learned Along
3:00PM – 3:15PM
the Way Whitney Smith, Collaborative Drug Discovery, USA
3:15PM – 3:30PM Antibody-Drug Conjugates Graham Garnett, Zymeworks, Canada
3:30PM – 3:50PM Coffee Break and Exhibitor Viewing
3:50PM – 4:00 PM ICBS Conference Welcome
4:00PM – 4:05PM Keynote Introduction
Keynote - Craig M. Crews, Yale University, USA
4:05PM – 4:50PM
PROTAC-mediated Protein Degradation: Making Problem Proteins Go Away
ICBS Opening Reception and Young Chemical Biologists’ Social – Shark Club, Library Room
5:00PM – 8:00PM
Please join us for a drink, hors d’oeuvres, and to network with your colleagues. A cash bar is available.

9:00AM – 9:15AM Welcome
Session I - Degradomics
9:15AM – 10:30PM
Chair: Shaomeng Wang
Shaomeng Wang, University of Michigan, USA
9:15AM – 9:40AM
Targeting Gene Transcription by PROTAC
Ting Han, National Institutes of Biological Sciences (NIBS), China
9:40AM – 10:15AM Anti-Cancer Sulfonamides Target Splicing by Inducing RBM39 Degradation Via Recruitment to the
DCAF15 Ubiquitin Ligase Receptor
Eric Fischer, Dana-Farber Cancer Institute, USA
10:15AM – 10:30AM Thalidomide Promotes Degradation of SALL4, a Transcription Factor Implicated in Duane Radial Ray
Syndrome
10:30AM – 10:50AM Coffee Break and Exhibitor Viewing
Session II – Glyco Chemical Biology
10:50AM – 12:10PM
Chair: David Vocadlo
David Vocadlo, Simon Fraser University, Canada
10:50AM – 11:15AM Development of Ultra-Sensitive Fret-Quenched Substrates for Quantitative Imaging of Glycoside
Hydrolases in Living Cells
Jennifer Kohler, University of Texas Southwestern Medical Center, USA
11:15AM – 11:40AM
Discovering Host Cell Receptors for Bacterial Toxins Using Photocrosslinking Sugars
Frederic Friscourt, University of Bordeaux, France
11:40AM – 11:55AM
Sydnone-Modified Monosaccharides for the Metabolic Oligosaccharide Engineering of Living Cells
Cristina Zamora, MIT, USA
11:55AM – 12:10PM Human Gut Microphysiological System Illuminates the Role of N-Glycans in Host-Pathogen
Interactions of Campylobacter jejuni

Open Panel Discussion
Chair: Rathnam Chaguturu, iDDPartners, USA
Academic/Industry Partnerships to Promote Drug Discovery Through Chemical Biology
1:15PM – 1:55PM Panel:
Doug Auld, Novartis USA, Scott Wolkenberg, Merck, Melvin Reichman, Lankenau Institute, Haian Fu,
Emory University, Shaomeng Wang, University of Michigan, Rima Al-awar, Ontario Institute of Cancer
Research, Yves Auberson, Novartis/EFMC Switzerland
1:55PM – 2:10PM Conference Updates
Session III – Computational Chemical Biology
2:10PM – 3:15PM
Chair: J.B. Brown
J.B. Brown, Kyoto University, Japan
2:10PM – 2:35PM Active Learning of Ligand-Target Interactions to Build Minimally Complex Yet Maximally Predictive
Interaction Models
Albert Antolin, Institute of Cancer Research, UK
2:35PM – 3:00PM
Probe Miner: Objective, Quantitative, Data-Driven Assessment of Chemical Probes
Andrey Ivanov, Emory University, USA
3:00PM – 3:15PM Integrated Computational and Experimental HTA Approaches to Discover and Target NSD3-Mediated
Protein-Protein Interactions in Cancer
Session IV – Emerging and Other Topics
3:35PM – 4:55PM
Chair: Sally-Ann Poulsen
Sally-Ann Poulsen, Griffith University, Australia
3:35PM – 4:00PM
Development of Chemical Probes for Visualising DNA Synthesis in Complex Cellular Systems
Milka Kostic, Dana-Farber Cancer Institute, USA
4:00PM – 4:25PM
Chemical Probes – Re-thinking our Ecosystem
Scott Lovell, University of Kansas, USA
4:25PM – 4:40PM Structure Guided Development of BfrB-Bfd Protein:Protein Interaction Inhibitors: a Novel Target for
Antibiotic Development
Jeremy Baskin, Cornell University, USA
4:40PM – 4:55PM
Impact: a Chemical Strategy for Imaging Phospholipase D and Phosphatidic Acid Signaling
Poster Session on Balcony Level: Odd Numbered Presentations
5:00PM – 7:00PM
Please join us for hors d’oeuvres and to network with your colleagues. A cash bar is available.

9:00AM – 9:05AM Conference Updates
ICBS 2018

Session V – The Chemical Biology – Medicinal Chemistry Continuum
9:05AM – 10:25AM
Chair: Yves Auberson
Scott Wolkenberg, Merck, USA
9:05AM – 9:30AM Reducing Limitations in the Design of Photoaffinity Labeling Reagents: Development of a Diazirine-
Compatible Cross Coupling Reaction
Rima Al-awar, Ontario Institute for Cancer Research, Canada
9:30AM – 9:55AM
Discovery and Optimization of OICR9429, a WDR5 Chemical Probe
Casey Krusemark, Purdue University, USA
9:55AM – 10:10AM In Vitro Selection Assays: New Approaches and Applications in DNA-Encoded Libraries and Activity-
Based Probes
Masahiko Ajiro, Kyoto University Graduate School of Medicine, Japan
10:10AM – 10:25AM CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 with a Therapeutic Effect for HPV-
Induced Neoplasia
Session VI – Synthetic Biology
10:45AM – 12:15PM
Chair: Jason Micklefield
Jason Micklefield, Manchester University, UK
10:45AM – 11:10AM Diversification of Natural and Non-Natural Products Using Engineered Biosynthetic Pathways and
Enzymes
Michelle Chang, University of California, Berkeley, USA
11:10AM – 11:35AM
Synthetic Biology Approaches to New Fluorine Chemistry
Kaity Ryan, University of British Columbia, Canada
11:35AM – 12:00PM
Building Non-Proteinogenic Amino Acids
Florian Mayerthaler, University of Münster, Germany
12:00PM – 12:15PM
Understanding Conformational Changes in Nonribosomal Peptide Synthetases
Session VII – iPSC Chemical Biology
1:15PM – 2:35PM
Chair: Steve Haggarty
Steve Haggarty, Harvard University, USA
1:15PM – 1:40PM
Humanizing CNS Drug Discovery Using Patient-Specific Stem Cells Models
Anne Bang, Sanford Burnham Prebys Medical Discovery Institute, USA
1:40PM – 2:05PM Phenotypic Screening of Human Induced Pluripotent Stem Cell Derived Neurons: Balancing
Throughput With Relevance
Paul Guyett, BrainXell, USA
2:05PM – 2:20 PM ALS Drug Discovery Via High-Throughput Phenotypic Screening Using iPSC-Derived Human Motor
Neurons
Kimberly Snyder, STEMCELL Technologies, Canada
2:20PM – 2:35 PM
Chemical-Induction and Maintenance of Naïve-like Human Pluripotent Stem Cells
2:35PM – 3:10 PM ICBS Business Meeting

3:40PM – 5:00PM Rising Stars
Rising Stars Session Introduction: ICBS Young Chemical Biologist Awards 2018
3:40PM – 3:45PM
Haian Fu, Chair of the Rising Star Selection Committee, Emory University, USA
Rising Star 1
3:45PM – 4:10PM Christina Woo, Harvard University, USA
Proximity-Directed O-GlcNAc Transferase for Protein-specific O-GlcNAcylation
Rising Star 2
4:10PM – 4:35PM Chu Wang, Peking University, China
Chemoproteomics Profiling Reveals the Anti-Steatosis Mechanism of a Natural Flavonoid
Rising Star 3
4:35PM – 5:00PM Michael Cohen, Oregon Health and Science University, USA
Decoding Protein Adp-Ribosylation Networks in Cells Using Chemical Genetic Approaches
Poster Session on Balcony Level: Even Numbered Presentations
5:00PM – 7:00PM
Please join us for hors d’oeuvres and to network with your colleagues. A cash bar is available.

9:00AM – 09:05AM Conference Updates
Session VIII – Synthetic Chemistry
9:05AM – 10:25AM
Chair: David Lupton
David Lupton, Monash University, Australia
9:05AM – 9:30AM
New Reactivity, New Structures...New Functions?
Dawei Ma, Institute of Organic Chemistry, China
9:30AM – 9:55AM
New Strategies for Synthesizing Bioactive Alkaloids
Shinichi Sato, Tokyo Institute of Technology, Japan
9:55AM – 10:10AM
Development and Application of Tyrosine Click Reaction
Ji-Shen Zheng, University of Science and Technology of China, China
10:10AM – 10:25AM Chemical Synthesis of Membrane Protein: Mirror-image Influenza A Virus Proton Channel M2 with
Channel Activity
10:45AM – 10:50AM Keynote Introduction
Keynote - Jörn Piel, ETH Zurich, Switzerland
10:50AM – 11:35AM
New Enzyme Tools From Uncharted Natural Product Space
Open Panel Session
Chair: Paul Clemons, Broad Institute, USA
Target Identification and Mechanism-of-Action Studies Using Chemical Biology
11:35AM – 12:15PM
Panel
Michael Finley, Janssen Research & Development, Bridget Wagner, Broad Institute, Andy Phillips, C4
Therapeutics, Scott Lovell, University of Kansas, Andrew Zhang, AstraZeneca
ICBS 2018

Session IX – Chemical Proteomics for Drug Target Engagement
1:15PM – 2:45PM
Chair: Michael Finley and Andrew Zhang
Andrew Zhang, AstraZeneca, USA
1:15PM – 1:40PM
Elucidating PARP Inhibitor Selectivity Using a PARP Family Affinity Matrix
Sherry Niessen, Pfizer, USA
1:40PM – 2:05PM
Applying Chemical Biology in the T790M-EGFR Program
Andy Philips, C4 Therapeutics , USA
2:05PM – 2:30PM
Targeted Protein Degradation: Tools for Target Evaluation and Therapeutic Applications
Y. George Zheng, University of Georgia, USA
2:30PM – 2:45PM
Bioorthogonal Chemical Probes to Interrogate Protein Acetylation
2:45PM – 3:00PM Poster and Other Awards
Session X – Biosensors and Imaging
3:20PM – 4:50PM
Chair: Jin Zhang
Jin Zhang, Univeristy of California, San Diego, USA
3:20PM – 3:45PM
A Suite of New Fluorescent Biosensors for Dynamic Visualization of Cell Signaling in Living Cells
Robert Campbell, University of Alberta, Canada
3:45PM – 4:10PM
New Colours and Applications of Genetically Encoded Biosensors to Probe Cell Signaling
Ellen Sletten, University of California, Los Angeles, USA
4:10PM – 4:30PM
Shortwave Infrared Fluorophores for Illuminating Biological Processes In Vivo
Poncho Meisenheimer, Promega, USA
4:30PM – 4:50PM
Selectivity Differences Between Cellular and Biochemical Kinase Analysis
4:50PM – 5:00PM Closing Remarks
Thank you to our conference sponsors
ICBS 2018
Keynote Speaker
Craig Crews
Dr. Crews is the Lewis Cullman Professor of Molecular, Cellular and Developmental
Biology and holds joint appointments in the departments of Chemistry and Pharmacology
at Yale University. He graduated from the U.Virginia with a B.A. in Chemistry and received
his Ph.D. from Harvard University in Biochemistry. Dr. Crews has a foothold in both the
academic and biotech arenas; on the faculty at Yale since 1995, his laboratory pioneered
the use of small molecules to control intracellular protein levels. In 2003, he co-founded
Proteolix, whose proteasome inhibitor, Kyprolis™ received FDA approval for the
treatment of multiple myeloma. Since Proteolix’s purchase by Onyx Pharmaceuticals in
2009, Dr. Crews has focused on a new ‘induced protein degradation’ drug development
technology, PROTACs, which served as the founding IP for his latest New Haven-based
biotech venture, Arvinas, LLC. Currently, Dr. Crews serves on several editorial boards and
is an Editor of Cell Chemical Biology. In addition, he has received numerous awards and
honors, including the 2013 CURE Entrepreneur of the Year Award, 2014 Ehrlich Award
for Medicinal Chemistry, 2015 Yale Cancer Center Translational Research Prize, a NIH
R35 Outstanding Investigator Award (2015) and the 2017 AACR Award for Outstanding
Achievement in Chemistry in Cancer Research.
PROTAC-mediated Protein Degradation: Making Problem Proteins Go Away

Enzyme inhibition has proven to be a successful paradigm for pharmaceutical development, however, it has several
limitations. As an alternative, for the past 16 years, my lab has focused on developing Proteolysis Targeting Chimera
(PROTAC), a new ‘controlled proteolysis’ technology that overcomes the limitations of the current inhibitor pharmacological
paradigm. Based on an ‘Event-driven’ paradigm, PROTACs offer a novel, catalytic mechanism to irreversibly inhibit
protein function, namely, the intracellular destruction of target proteins. This approach employs heterobifunctional
molecules capable of recruiting target proteins to the cellular quality control machinery, thus leading to their degradation.
We have demonstrated the ability to degrade a wide variety of targets (kinases, transcription factors, epigenetic readers)
with PROTACs at picomolar concentrations. Moreover, the PROTAC technology has been demonstrated with multiple
E3 ubiquitin ligases, included pVHL and cereblon.
Keynote Speaker
Jörn Piel
Jörn Piel received a PhD in Chemistry at the University of Bonn, Germany, and
conducted postdoctoral work with Bradley Moore and Heinz Floss at the University
of Washington, Seattle. He then became Research Group Leader at the Max Planck
Institute of Chemical Ecology in Jena, Germany, and Associate Professor of Bioorganic
Chemistry at the University of Bonn. Since 2013 he is Full Professor of Microbiology
at ETH Zurich. Research of his lab focuses on metabolic functions of “microbial dark
matter”, the investigation and utilization of new biosynthetic enzymology, and ecology-
and genome-based methods of natural product discovery.
New enzyme tools from uncharted natural product space

Most areas of the bacterial tree of life are functionally uncharacterized. These regions include numerous deep-branching
taxa that lack cultivated representatives and live in diverse habitats. Our lab uses metagenomic and single-cell-based
mining strategies to investigate whether this massive taxonomic and ecological diversity is a resource of metabolic novelty.
We have previously reported uncultured symbionts of marine sponges as a rich source of bioactive and biosynthetically
unusual compounds.1,2 The talk will present recent insights into the metabolic repertoire of ‘Entotheonella’ sponge
symbionts, a “talented” producer taxon with a rich and diverse chemistry comparable to that of streptomycetes. While
most of the biosynthetic pathways had no counterparts in known cultured bacteria, functional studies also revealed
mechanistically surprising enzymes that expand the chemical space of ribosomal peptide biosynthesis and have
widespread homologs in culturable prokaryotes.3-5 Implications for synthetic biology applications will be discussed.
[1] M. Wilson et al., Nature 2014, 506, 58.
[2] J.B. Cahn et al., Proc. Natl. Acad. Sci. U. S. A. 2018, 115, 1718.
[3] M. F. Freeman et al., Science 2012, 338, 387.
[4] M. F. Freeman et al., Nat. Chem. 2017, 9, 387.
[5] B .I. Morinaka et al., Science 2018, 359, 779.
ICBS 2018
Degradomics
Targeting Gene Transcription by PROTAC Anti-Cancer Sulfonamides Target Splicing
by Inducing RBM39 Degradation via
Recruitment to the DCAF15 Ubiquitin
SHAOMENG WANG Ligase Receptor
Warner-Lambert/Parke-Davis Professor
in Medicine, University of Michigan, Ann
Arbor, Michigan, USA
TING HAN
National Institute of Biological Sciences
The proteolysis targeting chimera (PROTAC) strategy has Beijing, China
emerged as a promising new approach for target validation and
for the discovery of potential new therapeutics. In this lecture,
I will present our recent efforts to target gene transcription by
PROTAC. I will highlight the key differences between protein Recent cancer genome sequencing efforts have identified
inhibitors and degraders, as well as the use of the PROTAC mutations in pre-mRNA splicing factors and prompted active
strategy to target those truly undruggable targets, including efforts to discover splicing inhibitors as a new strategy for treating
transcriptional factors. cancer. Many of the proteins important for splicing, however,
have no enzymatic activity and are thus challenging to inhibit via
Abstract Author Biography small molecules. We discovered that a class of clinically tested
anti-cancer sulfonamides (collectively named as SPLicing
Shaomeng Wang has been working on the discovery and inhibitor sulfonAMides (SPLAMs)) functions by promoting the
development of novel small-molecules therapeutics for more interaction between the splicing factor RBM39 and the CUL4-
than 20 years and is currently the Director of the Michigan DCAF15 E3 ubiquitin ligase, leading to polyubiquitination and
Center for Therapeutic Innovation. His research focuses on proteasomal degradation of RBM39. Mutations in RBM39
targeting protein-protein interactions which regulate apoptosis reduce its interaction with CUL4-DCAF15, increase its stability
and has resulted in the discovery and advancement of 6 and confer resistance to SPLAMs. RBM39 is essential for pre-
compounds into Phase I/II clinical development targeting Bcl-2/ mRNA splicing and inactivation of RBM39 by SPLAMs results in
Bcl-xL, MDM2 and IAP proteins. In more recent years, he has aberrant pre-mRNA splicing. Cancer cell lines originating from
expanded his research program to target a number of PPIs, the hematopoietic and lymphoid lineages frequently exhibit
which regulate epigenetics, including histone readers, writers sensitivity to SPLAMs, and their response to SPLAMs can be
and erasers, and have advanced several classes of compounds predicted by the expression levels of DCAF15. Taken together,
into advanced preclinical development. our studies reveal RBM39-DCAF15 as the target of SPLAMs,
Dr Wang has co-founded four UM start-up companies to help and identify DCAF15 expression as a potential biomarker to
bring drugs into clinical development and the marketplace; and guide clinical trials of SPLAMs.
has published >280 peer-reviewed papers and is an inventor of
50 issued US patents and international patents. He was elected Abstract Author Biography
as Fellow of the National Academy of Inventors in 2014 and is
the 2014 University of Michigan Distinguished Innovator. Dr. Han received a BS degree at Tsinghua University in 2006
and a PhD degree at University of Michigan in 2013. He was a
Life Sciences Research Foundation Fellow at UT Southwestern
before joining NIBS, Beijing as an assistant investigator in 2017.
Thalidomide Promotes Degradation of We show that IMiDs disrupt a broad transcriptional network
through induced degradation of multiple yet unknown C2H2zinc
SALL4, a Transcription Factor Implicated in finger transcription factors, including SALL4, a member of the
Duane Radial Ray Syndrome Spalt-like family of developmental transcription factors. Strikingly,
heterozygous loss of function mutations in SALL4result in a
human developmental condition that phenocopies thalidomide
induced birth defects such as absence of thumbs, phocomelia,
ERIC S. FISCHER defects in ear and eye development, and congenital heart
Dana-Farber Cancer Institute/Harvard disease. We find that thalidomide induces degradation of
Medical School SALL4 exclusively in humans, primates and rabbits, but not in
Boston, United States rodents or fish.
Our study provides a first mechanistic link for the species-
specific pathogenesis of thalidomide syndrome. Moreover, the
Frequently used to treat morning sickness, the drug thalidomide surprising expansion in substrate repertoire for pomalidomide,
led to the birth of thousands of children with severe birth defects. suggest that IMiDs exhibit a large degree of polypharmacology
Despite their teratogenicity, thalidomide and related IMiD drugs contributing to both efficacy and adverse effects. In turn, the
are now a mainstay of cancer treatment, however, the molecular discovery that IMiDs target an unanticipated large set of C2H2zinc
basis underlying the pleiotropic biology and characteristic birth finger proteins with significant differences between thalidomide,
defects remains unknown. IMiDs exert their therapeutic effect lenalidomide, pomalidomide and CC-220, suggests that this
by recruiting neo-substrates to the CRL4CRBN ubiquitin ligase, chemical scaffold holds the potential to target one of the largest
and hence provide clinical proof of concept for the rapidly families of human transcription factors.
emerging field of targeted protein degradation. Despite clinical
success, and widespread use as PROTAC constituent, the full Abstract Author Biography
target repertoire of IMiDs remains elusive. Here we set out to
establish the full repertoire of IMiD dependent substrates using Eric Fischer, PhD, received his doctorate in biology from the
a large scale proteomics approach. University of Basel (Switzerland) in 2013. In 2015 Dr. Fischer
joined the faculty of Harvard Medical School and the Dana-Farber
Using multiplexed mass spectrometry-based proteomics, we
Cancer Institute to continue his research using a multidisciplinary
conduct a large scale screen in a panel of cancer cell lines
approach centered on structural biology, chemical biology, and
and human embryonic stem cells for targets of thalidomide,
proteomics. Research in his lab focusses on understanding
lenalidomide, pomalidomide, CC-885, CC-220, and a set of
the role that the post-translational modification with ubiquitin
degrader/PROTAC molecules. Targets are validated using
plays in cellular processes, development and disease, and the
biochemical and cell biological tools.
development of novel pharmacologic strategies targeting the
ubiquitin machinery.
Notes
ICBS 2018
Glyco Chemical Biology

Development of Ultra-Sensitive Fret- Centre for High-Throughput Chemical Biology (HTCB) at SFU.
He received his PhD from the University of British Columbia and
Quenched Substrates for Quantitative was a postdoctoral fellow at UC Berkeley. Vocadlo joined SFU
Imaging of Glycoside Hydrolases in Living in 2004 where his team focuses on developing new chemical
Cells tools to improve our understanding of how carbohydrates
influence cell function, with particular emphasis on their roles
in neurodegenerative diseases. His pioneering research at the
interface of chemistry and glycobiology spans fundamental
research in enzymology through to translational preclinical
DAVID VOCADLO animal studies. He and his team have been recognized with a
Simon Fraser University number of national and international awards. His SFU research
Burnaby, Canada was cornerstone technology for co-founding of Alectos
Therapeutics, which has since partnered with Merck to advance
compounds to the clinic to combat neurodegenerative diseases.
Tunable Förster resonance energy transfer (FRET)-quenched

Discovering Host Cell Receptors for
substrates are useful for monitoring the activity of various enzymes
within their relevant physiological environments. Development of Bacterial Toxins Using Photocrosslinking
FRET-quenched substrates for glycosidases, however, has been Sugars
hindered by their constrained pocket-shaped active sites. The
emerging relevance of this large class of enzymes in a range of
human diseases is prompting increased interest in developing
technologies to monitor glycosidases in cells and tissues. In this
presentation we will discuss our recent progress in the design of JENNIFER KOHLER
UT Southwestern
substrates that overcomes this problem. Among these designs
Dallas, USA
we will highlight the invention of Bis-Acetal-Based Substrates
(BABS) that bear a hemiacetal aglycon leaving group that tethers
fluorochromes in close proximity, also positioning them distant
from the active site pocket. Following cleavage of the glycosidic
bond, the liberated hemiacetal spontaneously breaks down, Many pathogenic bacteria secrete protein toxins that recognize
leading to separation of the fluorophore and quencher. The intact glycosylated receptors on the surface of host cells. While
substrates show remarkably efficient quenching efficiency of physiologically significant, the interactions between bacterial
greater than 99.5%. These dark to light substrates are efficiently toxins and host glycoconjugates are often low affinity, and
turned over by various enzymes in vitro and kinetics experiments therefore difficult to characterize using traditional biochemistry
reveal that the first formed hemiacetal product rapidly breaks methods.Methods : To solve this challenge, we developed
down, allowing monitoring of enzyme activity. Moreover, the photocrosslinking analogs of monosaccharides, including
various substrate designs we describe are also processed sialic acid and N-acetylglucosamine (GlcNAc), and developed
in living cells, enabling quantitative monitoring of glycosidase strategies to incorporate these sugars into glycoconjugates
activity in their native environment. We expect this strategy to of cultured mammalian cell lines.Results : Activation of the
be broadly useful for the development of substrate probes for photocrosslinking functional group leads to covalent crosslinking
monitoring glycosidases, as well as a range of other enzymes with neighboring molecules. Crosslinked complexes can
having constrained pocket-shaped active sites. be isolated and analyzed by a variety of methods, including
immunoblot and proteomics analysis.Conclusion : This
approach can be used to covalently crosslink bacterial toxins
Abstract Author Biography
to their host cell receptors, and more broadly to discover the
Dr. David Vocadlo is a professor in the Departments of interaction partners of glycosylated molecules. I will discuss
Chemistry and Molecular Biology and Biochemistry. He holds strategies for incorporating photocrosslinking sugars into host
a Tier I Canada Research Chair in Chemical Biology at Simon cell glycoconjugates, as well as the application of these tools to
Fraser University (SFU) where he is also Co-Director of the define receptors for cholera and pertussis toxins.
Abstract Author Biography Abstract Author Biography

Jennifer Kohler’s research group develops chemical biology After completing a PhD in chemistry in 2009 on asymmetric
methods to understand biological functions of glycosylated organometallic and organic catalysis with Prof. Pavel Kocovsky
molecules. Methods include photocrosslinking sugar technology, (University of Glasgow, UK), I transitioned to the field of Chemical
which has been used to define glycan-mediated interactions. Biology during my postdoctoral fellowship (2008-2014) in
the laboratory of Professor Geert-Jan Boons at the Complex
Carbohydrate Research Center (GA, USA), where I developed
Sydnone-Modified Monosaccharides for novel chemical probes for imaging the glycome in living cells.
the Metabolic Oligosaccharide Engineering In 2014, I obtained a Junior Chair in Chemical Biology from the
of Living Cells University of Bordeaux, France (INCIA lab, CNRS UMR 5287)
and was recently recruited as a group leader at the European
Institute of Chemistry and Biology (IECB) in Bordeaux. I recently
received the prestigious CNRS-ATIP-Avenir award. My research
FREDERIC FRISCOURT focuses on using organic chemistry to develop novel selective
University of Bordeaux - CNRS UM5287, tools that can probe the influence of glycans notably in healthy
European Institute of Chemistry and vs diseased states.
Biology
Pessac, France
Human Gut Microphysiological System
Illuminates the Role Of N-Glycans in Host-
The bioorthogonal chemical reporter strategy, which elegantly Pathogen Interactions of Campylobacter
combines the use of metabolically labeled azido sugars and
1,3-dipolar cycloadditions with strained alkynes, is emerging
jejuni
as a versatile technology for the labeling and visualization of
glycans. Advantages of cyclooctyne-based probes encompass
their high reactivity, non-toxicity (metal-free conditions) and
synthetic modularity. However, azides have been shown to CRISTINA ZAMORA
react, to varying degrees, with biological functionalities such Massachusetts Institute of Technology,
as thiols. This inherent instability makes the azide functionality USA
a precursor for the potential accumulation of secondary
metabolites with unknown biological effects. In order to address
this limitation, while keeping the advantages of the cyclooctyne
framework as the reactive probe, we decided to investigate the A human intestinal immune-competent micro-physiological
utilization of other stable 1,3-dipoles as novel reporter. system was employed to the study of NCTC 11168 Campylobacter
In this context, we present herein the utilization of 3,4-disubstituted jejuni pathogenicity, through the lens of its N-linked protein
sydnones, a singular class of aromatic mesoionic dipoles, as glycosylation (Pgl) pathway. The ability of this Gram-negative
novel chemical reporters for the metabolic oligosaccharide enteropathogen to infect and colonize the intestinal trats of avians
engineering (MOE) of living cells (Figure). By employing chemical and murine model organisms has been directly linked to the Pgl
and enzymatic strategies, the reporter was appended to various pathway, but the exact role of C. jejuni N-glycans in causing
monosaccharides in order to study their metabolic invorporation disease in humans is unclear.
into glycoconjugates in living mammalian cells. To address this, an accessible tissue construct more closely
Introduction of the sydnone moiety onto various metabolic resembling human intestinal epithelia was employed to
monosaccharides demonstrated that not only its positioning on characterize several changes in C. jejuni epithelial invasion,
the sugar scaffold, but also on the class of carbohydrates, was immunogenicity, and virulence factor composition and function.
of prime importance for a successful incorporation of the novel This tripartite co-culture of C2bbe1, HT29-MTX, and macrophage-
reporter into cell-surface glycoconjugates. derived mature dendritic cells, results in a mucin layer, intestinal
epithelia and associated innate immune component.
Due to its high biological stability and specific glycan incorporation,
this novel chemical reporter will significantly expand our chemical Pgl knockout ΔpglE, lacking in cell-surface N-linked
biology toolbox for the visualization of labeled glycoconjugates. heptasaccharides, was found 100-fold less capable of adhering
to and invading this intestinal model in cell infectivity assays.
ICBS 2018
Chemokine and cytokine quantification by immunoassay Abstract Author Biography

revealed glyco-deficient strains ΔpglD and ΔpglE elicited
decreased inflammation of the intestinal epithelium, but increased Dr. Cristina Y. Zamora graduated from Boston College with
inflammation of the innate immune component of this tissue a Bachelors of Science degree in Chemistry. In 2008, she
construct of up to 25-fold. Virulence-associated outer membrane started her graduate work in the Department of Chemistry at
vesicles produced by wildtype and ΔpglE 11168 C. jejuni were Tufts University in the lab of Prof. Krishna Kumar. At Tufts, Dr.
shown to have differential composition and function by activity- Zamora developed novel fluorinated reagents for metabolic
based protein profiling analysis, with wildtype vesicles able to glycoengineering of cellular proteomes. She also biochemically
rescue ΔpglE infectivity to wildtype levels in infection experiments. characterized the activity and ligand preferences of several
human sialidases, enzymes differentially regulated in diseases
Overall, use of this tripartite system allowed for further such as prostate cancer. In 2014, she joined the lab of Prof.
characterization of the multifaceted importance of the Pgl Barbara Imperiali in the Department of Biology at MIT to
pathway in C. jejuni host-pathogen interactions within human characterize the relationship between the glycome of human
intestinal contexts. We anticipate these methods will be pathogen Campylobacter jejuni and its infectivity in humans.
broadly applicable to further studies of C. jejuni and to other From there, her research interests have broadened to targeted
enteropathogens of interest. This research was supported by small molecule drug delivery, directed evolution and protein
the NIH (R01-GM097241 to B.I., R01EB021908 to L.G.G.) and engineering, and alternative protein scaffold development.
DARPA (W911NF-12-2-0039 to L.G.G.).
Notes
Computational Chemical Biology

Active Learning of Ligand-Target Tested on GPCR, kinase, nuclear hormone receptor, and CYP450
families, the chemogenomic active learning methodology
Interactions to Build Minimally Complex Yet successfully builds highly predictive models of ligand-target
Maximally Predictive Interaction Models bioactivity using only 5~20% of the original matrix of activities
available. Further, it was tested in simulated prospective prediction
experiments and found to demonstrate good performance. A
convergence on predictive performance was found early on in
J.B. BROWN most datasets, suggesting that the extent of predictability for a
Kyoto University Graduate School of given chemical probe development project can be estimated
Medicine efficiently from a reduced amount of existing activity data.
Kyoto, Japan
Active learning represents a novel way to efficiently develop
novel chemical probes through use of feedback-driven, dynamic
modeling and prediction processes that converge efficiently on
Automated chemical screening has ushered in an era which the activity space of interest.
generates large ligand-target bioactivity matrices. As the size
of the matrices have grown, they have become increasingly Abstract Author Biography
more challenging to manually assess, and the use of statistical
pattern recognition (often called machine learning or currently J.B. Brown was a post-bachelor researcher in diagnostic
“AI”) to analyze the matrices for patterns is becoming common. radiology at the US National Institutes of Health after
The recent explosion in interest in deeply-layered neural network completing BS degrees in computer science and math at the
architectures (“deep learning”) has generated the impression University of Evansville. His Ph.D. thesis on machine learning in
that “bigger means better”, but this leads to a problem in chemoinformatics and bioinformatics was awarded from Kyoto
interpretation for chemical biology. Further, big data does not University in 2010. After post-docs in computational biophysics
implicitly carry a guarantee of extra benefit. To investigate the and pharmacoinformatics, he became an assistant professor
opposite, that is - how small and simple a machine learning can in the Department of Systems Onco-Informatics of the Kyoto
be that is yet still predictive, we have developed the technique University Graduate School of Medicine in 2014, and 18 months
of ligand-target active learning. later, was awarded an independent position within the same
graduate school, where he started the Life Science Informatics
We implement classification-type (yes/no) active learning by Research Unit. His research mixes chemoinformatics, clinical
separating chemogenomic ligand-target Ki or IC50 bioactivity informatics, and medical bioinformatics, with an emphasis on
matrices into strong and weak pairs based on reasonable translational research topics supported by core data processing
criteria. A human-intepretable machine learning algorithm and statistical methods. Notably, he has been researching
known as the Random Forest employs an ensemble of decision methods in prediction of ligand-target interactions for a decade,
trees to identify patterns that are rules for distinguishing between and his recent “small data, simple model” methodologies and
the strong and weak binders. The “active learning” terminology results in have received attention in news services such as AAAS’
comes from the strategy of beginning with one strong and one EurkAlert and Japanese newspapers. His current research
weak binding pair each, iteratively adding one new ligand-target interests are in identification of small molecule modulators of
pair at a time, and subsequently re-updating the decision tree immune response, and human-less fully automatic wet-dry
rules needed to separate the strong and weak binders. This bioactivity landscape exploration and knowledge extraction.
is in constrast to the “full deck” dumping of all ligand-target J.B. is a member of the Japanese Society for Chemical Biology
bioactivities into a single, monolithic model. and the Chemical Society of Japan.
ICBS 2018
Probe Miner: Objective, Quantitative, Data- the understanding of drug (poly)pharmacology so that currently
available drugs are better employed and the development safer
Driven Assessment of Chemical Probes and more efficacious anti-cancer therapeutics.
Integrated Computational and

ALBERT A. ANTOLIN Experimental HTA Approaches to Discover
The Institute of Cancer Research,
London (UK) and Target NSD3-Mediated Protein-Protein
London, United Kingdom Interactions in Cancer
Chemical probes are important widely-used reagents in

chemical biology for understanding biological systems and ANDREY IVANOV
for target validation. However, selection of chemical probes Emory University
Atlanta, United States
is largely subjective and prone to historical and commercial
biases. Despite many publications discussing the aspirational
properties of chemical probes and the proposal of ‘fitness
factors’ to be considered when assessing chemical tools,
scientists often select probes through web-based searchers The recent advances in cancer genomics engaged with the
or previous literature that are heavily biased towards older expanded landscape of oncogenic protein-protein interaction
and often flawed probes our use vendor catalogues that do (PPI) network have revealed the tumor heterogeneity and
not discriminate between probes. Here, we analyse the scope complexity of the oncogenic signaling. To enhance our
and quality of published bioactive molecules and uncover large understanding of cancer biology and discover novel therapeutic
biases and limitations of chemical tools in public databases that strategies, new effective chemical probes for oncogenic PPIs are
need to be urgently addessed and should be always considered urgently needed. Toward this goal we developed a highly robust
when using chemical tools. We also provide the online Probe high-throughput PPI screening platform and established a PPI
Miner resource (http://probeminer.icr.ac.uk) capitalising on the network of cancer-associated proteins, termed OncoPPi. The
plethora of public pharmacological data to enable quantitative, OncoPPi links the cancer driver genes, both oncogenes and tumor
unbiased, objective, data-driven assessment of chemical suppressors and allows to identify new tumor dependencies
probes and complement expert-curated approaches. We to inform novel strategies for therapeutic interventions. As one
assess >1.8m compounds for their suitability as chemical example, the OncoPPi has revealed a new interaction between
tools against 2,220 human targets, demonstrating that large- MYC oncogene and NSD3 protein, which plays a critical role in
scale public data can contribute to improve chemical probe regulation of chromatin remodeling through a direct association
assessment and prioritization to empower researchers in the with BRD4. Inhibition of interactions of NSD3 with MYC and
selection of chemical tools for biomedical research and target BRD4 by small molecules would provide new tools to investigate
validation. the NSD3-dependent tumorigenesis, and will facilitate cancer
drug development. Here we present a novel integrative platform
Abstract Author Biography to discover novel chemical probes for NSD3 signaling in cancer.
It includes:
Dr. Albert Antolin holds a BSc. and MSc. in Organic Chemistry
• Computational virtual screeing
from Ramon Llull University (Spain). After working as a
• Bioinformatics analysis of cancer genomics data
molecular modeller in the pharmaceutical industry for two
• Protein-protein interaction screening
years (Laboratorios Salvat), Albert undertook a European PhD
• High-throuput fluorescence resonance energy transfer assay
in Pharmacoinformatics at Pompeu Fabra University (Spain).
Subsequently, Albert moved to The Institute of Cancer Research We have developed and optimized a time-resolved fluorescence
(London, UK) with a Marie Curie Tecniospring postdoctoral resonance energy transfer (TR-FRET) assay to monitor the
fellowship. Since 2017, Albert has been a Sir Henry Wellcome interaction of NSD3 and MYC in miniaturized 1536-well ultra-
Fellow at the Institute of Cancer Research. His main lines of high-throughput screening (uHTS) format. To identify compound
research include the application of computational methods to the scaffolds required for the efficient disruption of NSD3 PPIs, we
development, characterisation and selection of chemical probes, have developed novel computational workflow that combines
classical cheminformatics approaches with the large-scale of Chemistry, and his Ph.D. in Organic Chemistry and
cross-validation virtual screening methods. Based on the Computational Chemistry from Institute of Physiologically Active
promising data from our pilot screening, we have launched a Compounds in Russia. Dr. Ivanov carried out his postdoctoral
large-scale screening campaign to discover potent and selective research at the National Institute of Diabetes and Digestive and
inhibitors of NSD3 interactions. Kidney Diseases of the NIH working on medicinal chemistry and
drug design for GPCRs. In 2011 he joined the Emory Chemical
Together, the OncoPPi network serves as a powerful resource to
Biology Discovery Center and the Department of Pharmacology
uncover new cancer vulnerabilities on oncogenic PPIs. OncoPPi
at Emory University and now he leads the Computational
Network has revealed new mechanism to control MYC-driven
Chemical Biology and Systems Pharmacology team at the
program through the protein-protein interaction with NSD3.
ECBDC. Dr. Ivanov is the recipient of NIH Fellows Award for
The integration of our experimental and computational high-
Research Excellence, and the Emory University Research
throughput approaches provides a robust platform to discover
Committee Award, and Emory Winship Cancer Institute Fadlo
novel inhibitors of challenging PPIs to facilitate anti-cancer drug
R. Khuri Translational Research Award. He represents Emory
development.
University in the NCI Cancer Target Discovery and Development
Network Data Harmonization and Informatics Portal Group
Abstract Author Biography (CTD2 D-HIP) and in the CTD2 Dashboard Working Group. Dr.
Ivanov has authored or co-authored over 40 manuscripts and 3
Andrey A. Ivanov, Ph.D. is an Assistant Professor in the
book chapters. His group utilizes state-of-the-art bioinformatics,
Department of Pharmacology and Emory Chemical Biology
computational modeling, and systems biology approaches to
Discovery Center (ECBDC). He received his Masters degree
understand molecular connections among biological pathways
in Chemistry from the Moscow State University, Department
to facilitate drug target discovery and therapeutic development.
Notes
ICBS 2018
Emerging and Other Topics

A Small Molecule Binder-Based Approach chemistry approaches to harness the properties of small
molecules as tools to address human disease. Her research
to Drug Discovery in Chemical Biology goal is to discover new small molecules either as therapies
(where current therapies are not available or are not effective)
or as chemical probes (that further contribute to understanding
complex biology) associated with cancer and infectious disease.
SALLY-ANN POULSEN
Griffith University, Griffith Institute for A significant outcome of her research has been the
Drug Discovery development of new small molecules as chemical probes that
Brisbane, Australia enable researchers to track and visualize DNA synthesis across
complex mammalian and parasite systems – without chemical
probes these systems are otherwise ‘invisible’ to researchers.
The application of her novel pro-label methodology drew
Fragment based drug discovery (FBDD) is a recently validated inspiration from the pro-drug:drug relationship of medicinal
approach to identify small molecules as better chemical starting chemistry and constitutes a critical advance in chemical biology
points for drug discovery. Since 2005, fragment screening has capability as it overcomes limitations of other probes, allowing
resulted in three FDA approved drugs and more than 30 drug greater applications in biology.
candidates in clinical trials. The take-up of FBDD in academia,
Sally-Ann has also developed and implemented native state
biotech and pharma is growing owing to this success.
mass spectrometry as an alternative and complementary
Fragment screening is vastly different to high throughput enabling technology in drug discovery, specifically to advance
screening (HTS), where hit compounds are relatively strong the detection of small molecules that bind to proteins where
binders (KDs in the nM to µM range) commonly detected by detection has been challenging or not possible by mainstream
functional output in a biochemical assay. In contrast, fragment technologies. Using this method she has discovered a novel
screening is contingent on robust analytical methods to identify inhibitor chemotype for an enzyme family that has been
very weak protein−fragment binding interactions with KDs as dominated for more than 70 years by one compound class of
low as mM. A number of biophysical techniques have been inhibitor.
used to screen fragment libraries for small molecule binding
partners for proteins. The most popular techniques to observe
these binders include NMR, SPR and X-ray crystallography. The
Chemical Probes – Re-Thinking our
use of mass spectrometry for fragment screening has remained Ecosystem
relatively underexplored. This presentation will highlight the
attributes of mass spectrometry as a complementary screening
method in fragment-based drug discovery. It will also identify the
scope for applying this method to find small molecule binders
that are functionally silent in classical assays.
MILKA KOSTIC
Dana-Farber Cancer Institute
REFERENCES Boston, United States
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Chemical probes, tool compounds that can be used to interrogate
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Peat, T.S.; Poulsen, S.-A. Identification of a New Zinc Binding Chemotype
one of the key contribution that chemical biology as a field
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continues to make to the broader life science and biomedical
research communities. As such, chemical biologists have been
Abstract Author Biography investing resources and grass-roots efforts into defining what
constitutes a chemical probe, and developing guidelines for
Sally-Ann Poulsen is Professor of chemistry and Senior
characterization and validation. However, although standards
Research Leader at Griffith Institute for Drug Discovery, Griffith
have emerged, their wide adoption, implementation and
University, Brisbane, Australia. Sally-Ann applies modern
enforcement are lagging behind. More importantly, in practice, of P. aeruginosa and release of iron is facilitated by a 7 kDa
many biologists continue to use “discredited” chemical probes, ferredoxin (Bfd). The structure of the BfrB-Bfd complex revealed
also known as historic compounds thus generating unreliable a conserved protein-protein interface (PPI) poised for disruption
results and scientific conclusions. The talk will focus on some of the protein-protein interaction by small molecules. We have
of the big picture questions surrounding chemical probes, their developed small molecules that block the BfrB-Bfd interaction
use and standards, and present some ways in which we can and disrupt iron homeostasis in P. aeruginosa thus providing a
address current key challenges. novel route for antibiotic development.
Structural information of protein:protein complexes can facilitate
Abstract Author Biography the development of lead compounds by providing details
regarding specific molecular interactions at the atomic level. As
Milka Kostic, Ph.D. is the Program Director, Chemical Biology such, the structure of the BfrB-Bfd complex was determined
at Dana-Farber Cancer Institute, a Harvard Medical Schools which permitted analysis of the PPI and the development of a
affiliated hospital and research center in Boston, MA, USA. In training set of compounds that could potentially bind to the BfrB
this role, she supports a vibrant chemical biology program of surface and inhibit its interaction with Bfd. Fragment-based
about 120 scientists (faculty, postdocs, graduate students, drug design (FBDD) methods using STD-NMR were employed
staff scientists and technicians), who work tirelessly to develop to identify initial compounds that 1) bind to BfrB and 2) target
chemistry-inspired research tools, platforms and strategies, the PPI site. The compound binding mode was determined
to make new discoveries in basic biology, as well as translate using X-ray crystallography and guided chemical modification
these discoveries into improved clinical practice. Prior to Dana- of the initial fragment into larger compounds with higher binding
Farber, Dr. Kostic was the Editor of Cell Chemical Biology affinity for BfrB.
and Structure for more than a decade, thus supporting and
shaping chemical biology and structural biology communities. The structure of the BfrB-Bfd complex revealed that 12 Bfd
Dr. Kostic is a passionate advocate for chemical biology, and molecules bind to BfrB and provided mechanistic insight into iron
transport from the BfrB core. Notably, the BfrB surface undergoes
its transformative ability to accelerate basic and translational
minimal conformational changes and accommodates specific Bfd
discoveries on the chemistry-biology-medicine continuum. She
residues. The initial fragment compound was found to bind BfrB
is also committed to career development and well-being of early
with millimolar affinity at the PPI site. A new series of compounds,
career researchers, and promoting gender equality in science
based on the initial fragment, were found to bind BfrB with low
and society. She is an active blogger, and her main creative
millimolar affinity and inhibited iron release from BfrB.
outlet is cooking and crafting plant-based meals for her friends
and family! The structure of the BfrB-Bfd complex revealed a conserved
PPI that permitted the development of compounds that block
the protein-protein interaction. Initial compounds were identify
Structure Guided Development of BfrB- using FBDD methods and were further expanded into more
Bfd Protein:Protein Interaction Inhibitors: a potent inhibitors that disrupt iron homeostasis in P. aeruginosa
Novel Target for Antibiotic Development thereby providing a novel route for antibiotic development.

Dr. Scott Lovell has served as Director of the Protein Structure
SCOTT LOVELL Laboratory (PSL) at the University of Kansas (KU) for the past
University of Kansas decade and has 24 years of experience in the X-ray crystallography
Lawrence, United States
field. He received his Ph.D. from Purdue University in chemistry
where he was trained in X-ray crystallography and studied
the structural and optical properties of guest chromophores
and biomolecules oriented in organic crystalline matrices. His
The iron storage protein bacterioferritin (BfrB), present only in postdoctoral work at the University of Wisconsin-Madison was
bacteria, functions to regulate iron concentrations by storing focused on the structure determination of Tn5 transposase:DNA
iron and releasing it as needed for metabolic functions. The complexes in an effort to gain mechanistic insight regarding DNA
BfrB structure consists of alpha helical subunits that dimerize transposition. Subsequently, he managed an industrial structural
and further assemble into a functional 24-mer (440 kDa) biology group at deCODE biostructures, located in the Chicago
sphere-like structure that contains an 80 Å diameter core that area, overseeing all aspects of gene-to-structure projects for
can store up to 2,000 iron ions. BfrB is required for growth external commercial clients and internal projects, focused on
ICBS 2018
drug discovery and development. In addition he assisted in the This approach, which we have termed IMPACT (Imaging
maintenance and operation of a synchrotron beamline, operated Phospholipase D Activity with Clickable Alcohols via
by deCODE, at the Advanced Photon Source. As the Director Transphosphatidylation), has revealed pools of PLD activity at
of the PSL, his current laboratory collaborates with a diverse novel subcellular locations within individual cells and unexpected
range of investigators from various academic and industrial heterogeneity of PA signaling across cell populations. We are
institutions to obtain structural information of proteins using X-ray currently exploring and will present applications of IMPACT
crystallography and utilizes high throughput techniques to rapidly to elucidate novel mechanisms controlling PLD activation in
move projects from gene-to-structure. As such, the PSL has normal physiology and in disease.
completed over 250 protein crystal structures and coauthored
60 publications. Additionally, Dr. Lovell is a co-investigator on Collectively, our work highlights the importance of using
five NIH funded R01 grants aimed at inhibitor development and chemical strategies to directly visualize, with high spatial and
manages the structural biology work for these projects. temporal resolution, the subset of signaling enzymes that are
active.
Impact: a Chemical Strategy for Imaging

Phospholipase D and Phosphatidic Acid
Signaling Jeremy M. Baskin is the Nancy and Peter Meinig Family
Investigator in the Life Sciences and Assistant Professor in the
Department of Chemistry and Chemical Biology and the Weill
Institute for Cell and Molecular Biology at Cornell University in
Ithaca, New York. Born and raised in Montreal, Canada, Jeremy
JEREMY M. BASKIN
Cornell University received an S.B. degree (Phi Beta Kappa) from the Massachusetts
Ithaca, United States Institute of Technology in 2004, majoring in chemistry, minoring
in biology and music, and performing research with Stephen
Buchwald and Alice Ting. As an NSF and NDSEG predoctoral
fellow with Carolyn Bertozzi at UC Berkeley, Jeremy developed
Chemical imaging techniques have played instrumental roles in copper-free click chemistry and applied it to image glycans in
dissecting the spatiotemporal regulation of signal transduction developing zebrafish, earning his Ph.D. in chemistry in 2009.
pathways. Phospholipase D (PLD) enzymes affect cell Jeremy carried out postdoctoral research as a Jane Coffin Childs
signaling by producing the pleiotropic lipid second messenger fellow with Pietro De Camilli at the Yale School of Medicine on the
phosphatidic acid via hydrolysis of phosphatidylcholine. It cell biology of phosphoinositide lipid metabolism, discovering
remains a mystery how this one lipid signal can cause such that the mechanistic basis underlying a genetic disease
diverse physiological and pathological signaling outcomes, due featuring aberrant myelination is a defect in phosphoinositide
in large part to a lack of suitable tools for visualizing the spatial biosynthesis at the plasma membrane. Jeremy’s independent
and temporal dynamics of its production within cells. research program at Cornell, established in 2015, centers on
Here, we report a chemical strategy for imaging phosphatidic the chemical biology and cell biology of lipids and biological
acid synthesis by PLD enzymes in live cells. Our approach membranes. Using cross-disciplinary approaches, Jeremy’s
capitalizes upon the enzymatic promiscuity of PLDs, which we lab pioneers advances in chemical approaches to elucidate
show can accept bioorthogonally tagged, or clickable, alcohols novel signaling functions of lipid second messengers including
as reporters in a transphosphatidylation reaction. The resultant phosphatidic acid and phosphoinositides. Jeremy’s work has
clickable lipids are then fluorescently tagged using an appropriate been recognized by Beckman Young Investigator and NSF
bioorthogonal/click chemistry reaction, enabling visualization of CAREER awards as well as his selection as part of the “Future
cellular membranes bearing active PLD enzymes. of Biochemistry” special issue of Biochemistry.
The Chemical Biology – Medicinal Chemistry

Continuum
Reducing Limitations in the Design The robustness screen identified reaction conditions that gave
good yields of S-M coupling product while minimally perturbing
of Photoaffinity Labeling Reagents: the diazirine reporter fragment. This is significant because
Development of a Diazirine-Compatible diazirines themselves are reported as competent cross-coupling
Cross Coupling Reaction partners. The conditions were found to be highly scalable and
exhibited broad scope when applied to a chemistry informer
library of pharmaceutically relevant aryl boron pinacol esters.
Furthermore, these conditions were used to synthesize a known
diazirine-containing probe molecule with improved synthetic
SCOTT WOLKENBERG efficiency
Merck & Co., Inc.
Kenilworth, Univted States Limited synthetic methods have constrained molecular
design of PAL probes and results of labeling studies. A newly
developed S-M protocol reduces these limitations and provides
an alternative to published routes which rely on 3-4 step
sequences and/or very long reaction times.
Diazirine-based photoaffinity labeling (PAL) reagents are an
important class of chemical probes widely used to form stable
covalent adducts with proximal binding partners in complex Abstract Author Biography
biological mixtures. Despite their prominence, diazirines have
Scott Wolkenberg joined Merck Research Laboratories in West
been synthesized only by a limited set of methods, imposing
Point, PA, in 2003 and is currently Principal Scientist in the
significant constraints on the design of diazirine-containing
Chemical Biology group. Over the past 14 years, Scott and his
PAL probes. Convinced that available synthetic methods were
teams have been involved in the design and synthesis of multiple
compromising diazirine PAL probe design across a broad range
compounds entering preclinical development including Kv1.5
of studies, we investigated expanding the range of methods for
blockers for atrial fibrillation, GlyT1 inhibitors for the treatment of
their incorporation.
cognitive disorders, and a PET imaging agent for early diagnosis
Published diazirine PAL probes (n = 212) were analyzed of Alzheimer’s disease. Scott has been a project leader in the
according to reaction used for diazirine incorporation and lead optimization space as well as the target validation and lead
category of diazirine placement in probe versus unlabeled identification space. Scott has co-authored 43 peer-reviewed
parent pharmacophore. Despite the advantages of nesting publications, is co-inventor on 20 patent applications, and has
diazirines in the active pharmacophore, this design is the least participated in and organized conferences in the US and abroad.
common found in the literature. And, surprisingly, we found a He Chaired the 2015 Gordon Conference on High Throughput
near absence of metal-catalyzed cross coupling reactions for Chemistry and Chemical Biology. Scott was born and grew up
diazirine PAL probe synthesis. Because biaryls are prominent in in central New Jersey before attending Cornell University; he
biologically-active compounds, this suggests synthetic access graduated in 1998 summa cum laude in chemistry with a double
is a problem, and we investigated Pd-catalyzed cross coupling major in biology. He received a Ph.D. in organic chemistry from
of diazirine-containing aryl halides and boronic acids to form The Scripps Research Institute in La Jolla, CA, where he applied
biaryls, i.e. the Suzuki-Miyaura reaction (S-M). inverse-electron demand Diels-Alder reactions in total synthsis
in the research group of Dale L. Boger.
We conducted 1) an initial fragment-based robustness screen to
identify S-M conditions that give high cross-coupling efficiency
while not degrading aryl diazirines followed by 2) a survey of
pharmaceutically relevant substrates to define the scope and
limitations of the method.
ICBS 2018
Discovery And Optimization of OICR9429, In Vitro Selection Assays: New Approaches

a WDR5 Chemical Probe and Applications in DNA-Encoded Libraries
and Activity-Based Probes
RIMA AL-AWAR
Ontario Institute for Cancer Research
Toronto, Canada CASEY KRUSEMARK
Purdue University
West Lafayette, United States
At a fundamental level, gene expression is regulated by epigenetic

histone modifications. Histone methyltransferases catalyze the The in vitro selection of encoded libraries allows a collective
transfer of the methyl group from S-adenosylmethionine to specific querying of function for many molecules simultaneously. Inspired
lysine residues on histones. Mixed lineage leukemia 1 (MLL1) is a by natural selection-driven evolution, the signal for this assay is
methyltransferase that methylates lysine 4 on histone H3 (H3K4me3) DNA allele frequency change within a population in response
and is an important regulator of the haemopoietic system. to selective pressure. This approach has several advantages
Dysregulation of MLL1 is often associated with acute myeloid and over assays employed in traditional small molecule screening
lymphoid leukemias, making it an attractive therapeutic target. campaigns, such as improved throughput and lower cost. We
WD40 repeat protein 5 (WDR5) is a component of the multiprotein present an evaluation of in vitro selection assays with regard to
MLL1 complex and is essential for its methyltransferase activity, and their application to discovery from DNA-encoded libraries (DELs)
disruption of the WDR5/MLL1 interaction may therefore present and also to selection-based sensing, a new assay approach we
a viable therapeutic option for the treatment of MLL-dependent have developed that uses DNA-linked probes to detect enzyme
leukemias. Employing a structure-based drug design approach, activity by DNA sequencing or quantitative PCR.
we have identified potent and orally bioavailable inhibitors of the
WDR5/MLL interaction and demonstrated their efficacy in in vivo Selection assays included affinity purifications with immobilized
models. proteins. Using the chromodomains of the chromobox (CBX)
7 and 8 proteins as a model system, we evaluated the
robustness of affinity selections with a collection of DNA-
Abstract Author Biography linked ligands of known affinity and applied assays with DELs
Dr. Al-awar earned a PhD in synthetic organic chemistry of peptidomimetics. Also, we developed selection approaches
from North Carolina State University and did a post-doctoral for enzyme substrates for protein kinase (protein kinase A, Src,
fellowship at the University of North Carolina at Chapel Hill prior e.g.), protease (caspase), and transferase (farnesyltransferase)
to joining Eli Lilly and Company in 1995. In 2002, while still at Eli activities. Crosslinking selections were developed where protein
Lilly, Dr. Al-awar was promoted to Head in Discovery Chemistry targets are covalently conjugated to proteins via an active site-
Research and Technologies and later served as Head in Route labeling electrophile (fluorophosphonate) and implemented for
Selection in Chemical Product Research and Development. In detection of serine hydrolase activity.
July 2008 she joined the Ontario Institute for Cancer Research Results indicated critical considerations for sucessful
(OICR) to build a drug discovery program. She is now the implementation of selection assays. These included
Director and Senior Principal Investigator of OICR’s Drug minimization of background signal, absolute recovery of ligands
Discovery Program. Dr. Al-awar also serves as an Associate and substrates, and overall enrichment values. With affinity
Professor in the Department of Pharmacology and Toxicology selections, statistical analyses indicated low DNA tag bias and
at University of Toronto. suggested that assays are sufficiently robust for both ligand
discovery and for determination of quantitative structure-activity
relationships. DEL selections yielded novel, selective ligands to
CBX8. The development of substrate and crosslinking-based
selections allowed a general approach for enzyme activity
detection by DNA sequence analysis for the first time. Assays
were implemented for detection of several activites in cell
lysates and in a screen of 96 kinase inhibitors conducted by
DNA sequencing. We examined FIT-039 for its effect on HPV gene expression
in HPV+ cervical cancer cells. Primary keratinocytes monolayer
In conclusion, this work highlights the potential of the in vitro
and organotypic raft culture models were used to evaluate
selection assay both for ligand discovery in DELs and as a
HPV viral replication and cervical intraepithelial neoplasia (CIN)
general enzyme assay platform.
phenotypes. Preclinical pharmacokinetics and toxicity tests
for FIT-039 were also conducted. The anti-HPV effect of FIT-
Abstract Author Biography 039 was further examined in vivo, using HPV+ cervical cancer
xenografts.
Casey was born and raised in Pike County Illinois and received his
B.S. degrees (Chemistry and Crop Science) from the University FIT-039 inhibited HPV replication and expression of E6 and E7
of Illinois-Urbana-Champaign. He obtained his Ph. D. in viral oncogenes, restoring tumor suppressors p53 and pRb
Biochemistry at the University of Wisconsin-Madison in the area in HPV+ cervical cancer cells. The therapeutic effect of FIT-
of chemical biology under Peter Belshaw, with an emphasis on 039 was demonstrated in CIN model of an organotypic raft
new chemical tools for mass spectrometry-based proteomics. culture, where FIT-039 suppressed HPV18-induced dysplasia/
He then conducted postdoctoral training at Stanford University hyperproliferation with reduction in viral load. FIT-039 also
with Pehr Harbury and Patrick Brown working on the directed repressed growth of HPV16+, but not HPV- cervical cancer
evolution of synthetic chemicals. He began his independent xenografts without any significant adverse effects. Safety and
career in 2013 at Purdue University in the Department of pharmacokinetics of FIT-039 were confirmed for systemic and
Medicinal Chemistry and Molecular Pharmacology. His group topical routes.
works on applications of DNA-encoded libraries for both novel
FIT-039 showed potent anti-HPV activity without significant
ligand discovery and proteomic activity-based probes, with a
toxicity in our preclinical studies. Thus, FIT-039 is expected to
focus on protein kinases and chromodomains. Outside of work,
be a novel therapeutic for CIN to prevent cervical cancer. FIT-
Casey enjoys gardening, basketball, his two young children,
039 is currently evaluated in the phase I/IIa trial for anti-HPV
and cats.
activity in viral warts and further planned in CIN.
CDK9 Inhibitor FIT-039 Suppresses Viral Abstract Author Biography

Oncogenes E6 and E7 with a Therapeutic
I graduated Tohoku University development of technology
Effect for HPV-Induced Neoplasia in 2005, and received MSc degree in the graduate school of
life science in 2007. Then I moved to the Institute of Medical
Science of the University of Tokyo, where I received PhD degree
for the screening of a novel molecular target and evaluation
MASAHIKO AJIRO of small molecule compounds for breast cancer. In 2010,
Kyoto University Graduate School of I moved to the National Cancer Institute of NIH in the US as
Medicine postdoctoral fellow, pursuing RNA biology for application to drug
Kyoto, Japan
development. My studies there were focused on RNA splicing
regulations associated with disease condition, viral infection,
and drug resistance. In 2016, I joined to the Department
of Drug Discovery Medicine of the Kyoto University as an
Cervical cancer is one of the leading causes of cancer deaths
assistant professor to lead a research group for development
among women worldwide, and human papillomavirus (HPV)
of small molecule compounds targeting viral infection and
infection is the etiological cause in more than 95% of cases.
splicing-associated genetic diseases. My research goal is to
HPV induces tumorigenesis through viral oncogenes, which
provide a novel therapeutics for diseases currently without
depend on host cell factor cyclin-dependent kinase 9 (CDK9)
effective therapeutic options. In cooperation with Dr. Masatoshi
for their transcriptional activation. The purpose of this study is
Hagiwara, we demonstrated antiviral effect of CDK9 inhibitor
to assesses the therapeutic effect of newly developed CDK9
FIT-039 against human papillomavirus (HPV), which is currently
inhibitor FIT-039 for cervical malignancy by targeting HPV viral
investigated in the phase I/IIa trial for HPV-induced viral warts.
gene expression and replication.
ICBS 2018
Synthetic Biology
Diversification of Natural and Non-Natural Synthetic Biology Approaches to New
Products Using Engineered Biosynthetic Fluorine Chemistry
Pathways and Enzymes
MICHELLE CHANG
JASON MICKLEFIELD University of California, Berkeley, USA
University of Manchester
Manchester, United Kingdom
The catalytic diversity of biological systems provides enormous

Natural products often require further chemical modification, to potential for the use of living cells to provide new methods for
improve their biological activities or physicochemical properties, organic and inorganic synthesis. One fundamentally interesting
for therapeutic and other applications. However, many of the chemical phenotype is the ability of Streptomyces cattleya to
most promising natural products, particularly the polyketides catalyze the formation of C-F bonds. Because of the unique
and nonribosomal peptides are highly complex molecules which elemental properties of fluorine, site-selective fluorination has
offer limited opportunity for semi-synthesis, and are invariably emerged as a powerful tool for improving the efficacy of small-
inaccessible through total synthesis on the scale required for molecule drugs. Our group is interested in using a synthetic
drug development. Consequently, alternative biosynthetic biology approach to expand the scope of fluorinated natural
engineering approaches are required, which can enable the products by engineering pathways for their production from the
rapid structural diversification and optimisation of promising simple fluorinated building blocks provided by S. cattleya.
natural product scaffolds.
Synthetic biology, molecular genetics, enzymology and chemical Abstract Author Biography
biology methods are used.
Michelle is a professor at UC Berkeley in the Departments of
In this lecture our recent progress in biosynthetic engineering Chemistry and Molecular and Cell Biology. She received her
will be presented. In addition methods for using enzymes from Ph.D. from MIT, working with JoAnne Stubbe and Daniel Nocera,
biosynthetic pathways to create non-natural products will be and her postdoctoral training with Jay Keasling at UC Berkeley.
described. Her research group works at the interface of enzymology
and synthetic biology, with a focus on studying biological
New biosynthetic pathways to novel products will be presented.
fluorine chemistry, formation of mixed-valent nanomaterials
by directional-sensing bacteria, and processes involved in
Abstract Author Biography developing synthetic biofuel and monomer pathways. She
has received the Dreyfus New Faculty Award, TR35 Award,
Jason Micklefield is Professor of Chemical Biology within the
Beckman Young Investigator Award, NSF CAREER Award,
School of Chemistry and the Manchester Institute of Biotechnology
Agilent Early Career Award, NIH New Innovator Award, DARPA
at the University of Manchester. He graduated from the University
Young Faculty Award, Camille Dreyfus Teacher-Scholar Award,
of Cambridge in 1993 with a PhD in Organic Chemistry and
3M Young Faculty Award, Arthur Cope Scholar Award, and
then moved to the University of Washington, USA, as a NATO
Pfizer Award in Enzyme Chemistry.
fellow investigating various biosynthetic pathways and enzyme
mechanisms. In 1995 he began his independent research career
as a Lecturer in Organic Chemistry at Birkbeck College, University
of London before moving to Manchester in 1998. Jason has
made diverse contributions at the chemistry-biology interface
in the areas of biocatalysis, enzyme mechanisms, biosynthesis,
biosynthetic pathway engineering and development of RNA
based regulatory tools (riboswitches).
Building Non-Proteinogenic Amino Acids in Biological Chemistry in 2002. She then carried out graduate
studies at MIT, where she worked with Catherine Drennan to
solve the X-ray crystal structures of natural product biosynthetic
enzymes. From 2008-2010, was a postdoctoral fellow with
Bradley Moore at the Scripps Institution of Oceanography at the
KATHERINE RYAN University of California at San Diego. She became an Assistant
The University of British Columbia Professor in the Department of Chemistry the University of
Vancouver, Canada
British Columbia in 2011. Her group is interested in elucidating
biosynthetic pathways to heterocycle-containing molecules and
solving the structures of biosynthetic enzymes.
There are hundreds of naturally occurring amino acids, the

majority of which are not incorporated into proteins. Such non-
Understanding Conformational Changes in
proteinogenic amino acids have diverse structures and biological Nonribosomal Peptide Synthetases
activities and could be used to make unnatural peptides. Here I
will discuss my group’s work to elucidate biosynthetic pathways
to non-proteinogenic amino acids.
In vitro reconstitution, mechanistic enzymology, and high- FLORIAN MAYERTHALER
resolution protein X-ray crystallography University of Münster
Münster, Germany
First, I will describe my group’s work on the pathway to
L-piperazic acid, a non-proteinogenic amino acid containing
a cyclic hydrazine that is incorporated into a variety of non-
ribosomal peptides. We discovered that a heme-dependent
enzyme catalyzes N-N bond formation to give L-piperazic acid Nonribosomal peptide synthetases (NRPSs) are large modularly
from N-hydroxy-L-ornithine.1 Second, I will discuss our discovery organized enzymes that synthesize a plethora of therapeutically
of an enzyme pair that converts L-arginine to D-dehydroarginine important peptides. A module consists of multiple discrete
in the pathway to the antibiotic indolmycin and highlight the key domains that incorporate specifically one of over 530 different
role of an O2-, pyridoxal phosphate-dependent oxidase.2 I will monomers through a sequence of coordinated reactions
furthermore describe our high-resolution X-ray crystallography (1). During the catalytic cycle, the substrates are processed,
studies that allowed us to gather ‘snapshots’ during catalysis to covalently linked to the enzyme and then passed on to the next
understand how such PLP-dependent oxidases function.3 module. These diverse reactions necessitate that the domains
undergo multiple conformational changes that are highly
Across both projects, I will describe how we identified these dynamic and still tightly regulated. Currently, little is known
enzymes, the in vitro work that allowed us to elucidate their how the structural reconfigurations and interactions within and
functions, and the implications for our understanding of enzyme in-between domains are orchestrated (2). Initial studies have
catalysis. Furthermore, I will describe potential applications of described the interaction between the peptidyl carrier protein
our work in biocatalyst development and drug discovery work. (PCP) and the adenylation domain (3) but dynamic measurements
REFERENCES: that elucidate the regulation of the conformational changes
Du YL, He HY, Higgins MA, Ryan KS (2017) A heme-dependent
1 have been missing. However, this knowledge is required to
enzyme forms the nitrogen-nitrogen bond in piperazate. Nat. Chem. understand the coordination of the enzymatic cycle, and thus to
Biol. 13, 836-838. precisely engineer NRPS for combinatorial biosynthesis of new
2
Du YL, Singh R, Alkhalaf LM, Kuatsjah E, He HY, Eltis LD, Ryan KS products. In order to overcome this shortcoming we applied
(2016) A pyridoxal phosphate-dependent enzyme that oxidizes an Förster Resonance Energy Transfer (FRET) spectroscopy to
unactivated carbon-carbon bond. Nat. Chem. Biol. 12, 194-199. NRPS by either introducing the fluorophores genetically or using
3
Hedges JB, Kuatsjah E, Du YL, Eltis LD, Ryan KS (2018) Snapshots site-specific Michael-like addition with maleimides. This allowed
of the catalytic cycle of an O2, pyridoxal phosphate-dependent us for the first time to monitor in real-time and in solution crucial
hydroxylase. ACS Chem. Biol., 13, 965-974. interactions between substrates, the adenylation and the
PCP domain (4). FRET is a known technique to study protein
dynamics (5), but has not been applied to NRPS before due
to their size and complexity. Here we report further studies
Katherine Ryan received her B.Sc. from the University of Chicago on the dynamics of the domain alternation mechanism of
ICBS 2018
the adenylation domain. Using pyrophospatase and different Abstract Author Biography
combinations of substrates, we can control the current state of
the enzyme and the kinetics of the conformational changes and Florian received his MSc in science from the University of Münster
thereby study the directionality of NRPS. These investigations in organic chemistry and biochemistry. He has spent 4 months as
will foster our understanding of the NRPS machinery and, a visiting scientist in the Department of Chemistry at Princeton,
consequently, facilitate their bioengineering. and at Bayer HealthCare. Florian is currently completing his
PhD at the Institute of Biochemistry of the University of Münster
(1) S. Caboche et al., J. Bacteriol., 2010 (2) K. Weissman, in the lab of Dr. Henning Mootz where his research focuses on
Nat. Chem. Biol., 2015 (3) J. Zettler et al., FEBS J., 2010 (4) characterization of nonribosomal peptide synthetases.
J. Alfermann et al., Nat. Chem. Biol., 2017 (5) T. Heyduk, Curr.
Opin. Chem. Biol., 2002
Notes
iPSC Chemical Biology

Humanizing CNS Drug Discovery Using pathways. Continued expansion of a ‘living library’ of patient-
specific iPSC models coupled to electronic health records
Patient-Specific Stem Cells Models and deep clinicopathological phenotyping along with further
methodological optimization and development of improved
disease-relevant, quantitative assays have the potential
STEPHEN J. HAGGARTY to advance multiple phases of novel target discovery and
Harvard Medical School, Department therapeutic development for CNS disorders.
of Neurology, Chemical Neurobiology
Laboratory, Massachusetts General
Hospital Abstract Author Biography
Boston, United States
Dr. Stephen J. Haggarty is an Associate Professor of Neurology
at Harvard Medical School, an Associate Neuroscientist at
Advances in a combination of disciplines—chemical biology, Massachusetts General Hospital, and Director of the MGH
human stem cell biology, and human genetics—are impacting Chemical Neurobiology Laboratory in the Center for Genomic
both our understanding of fundamental human disease biology Medicine. Dr. Haggarty is also a Senior Associate Member of
and our ability to discover next-generation pharmacological the Broad Institute and Affiliate Faculty Member of the Harvard
agents targeting the root cause of disease. Perhaps nowhere Stem Cell Institute. He completed his PhD in the Department of
are these advances most significant and critically needed than Chemistry & Chemical Biology at Harvard University, and joined
the area of central nervous system (CNS) disorders. While there the faculty of HMS/MGH in 2006. Dr. Haggarty was named
has been an explosion of new genetic information revealing the Stuart & Suzanne Steele MGH Research Scholar in 2017.
insight into their etiopathogenesis, major gaps exist in the Dr. Haggarty’s research program operates at the interface of
translational of these observations to a deep understanding of neurology and psychiatry with a focus on dissecting the role of
the underlying disease biology, the discovery and validation of neuroplasticity and resiliency in health and disease. His efforts are
new targets for disease treatment or prevention, and improved guided by knowledge emerging from human genetics regarding
diagnoses. the root causes of disease and have led to the discovery of
novel chemical probes targeting the regulation of neurotrophic
In this context, patient-derived, induced pluripotent stem cell factor signaling, epigenetic regulation of neuronal gene
(iPSC) models are increasingly recognized as providing robust expression, neurogenesis, synaptogenesis, and proteostasis
and scalable ex vivo models systems of both rare and complex networks. A major emphasis of his is the use of reprogramming
polygenic CNS disorders. Such ex vivo models of human technology to create patient-specific, induced pluripotent stem
disease, combined with powerful omic technologies, pathway- cells (iPSCs) as ex vivo models of neurogenetic disorders.
focused phenotypic screening, and high-content, quantitative The ability to differentiate human iPSCs into neural networks
imaging, enable systematic probing of the physiology and with the capacity to form synapses and regulate genes in an
biochemistry of previously inaccessible cell types at specific activity-dependent manner provides powerful new avenues for
stages of CNS development. Moreover, similar to other areas studies of neuroplasticity, for understanding the neurobiology
of medicine, recent findings suggest the value of a paradigm of human disease, as well as for addressing the challenging
where therapies are first tested ex vivo for target engagement goal of discovering novel targets and next-generation, disease-
and disease-relevant functional signatures in patients’ cells modifying therapies using the principles of genomic medicine.
to stratify patient populations prior to testing in vivo in formal
clinical trials.
Here, I will provide select examples of programs within the
Chemical Neurobiology Laboratory at Harvard Medical School/
MGH seeking to characterize patient-specific iPSC models
of neurodegenerative and neurodevelopmental disorders
and identify targets for developing novel disease-modifying
therapeutics. Specific examples of small-molecule screens will
include efforts to probe mechanisms of neuroresiliency and
proteostasis, as well as large-scale screens of neurogenesis
ICBS 2018
Phenotypic Screening of Human Induced to joining SBP she served as Director of Stem Cell Research at
ViaCyte Inc, where she focused on developing stem cells as a
Pluripotent Stem Cell Derived Neurons: source of pancreatic cells to treat diabetes. Dr. Bang received
Balancing Throughput With Relevance a B.S. from Stanford University, a Ph.D. in Biology from UCSD,
and was a post-doctoral fellow at the Salk Institute.
ALS Drug Discovery Via High-Throughput

ANNE BANG
Sanford Burnham Prebys Medical Phenotypic Screening Using iPSC-Derived
Discovery Institute
La Jolla, United States
Human Motor Neurons
The lack of human-specific pre-clinical models of neurological PAUL GUYETT

disease is likely a factor that contributes to low rates of new BrainXell, Inc.
therapies entering clinical trials. Human induced pluripotent Madison, United States
stem cells (hiPSC) based models could potentially be used to
address this void and aid in the development of clinically useful
compounds. hiPSC are scalable, circumvent issues of species
specificity, and allow interrogation of differentiated features of Amyotrophic lateral sclerosis (ALS) is a neurodegenerative
human neural cell-types not reflected by immortalized lines. disease primarily affecting motor neurons. Unfortunately, there
Importantly, they can also carry disease traits in the context of are only two drugs approved to treat the condition, neither of
specific human genetic backgrounds, offering an opportunity to which increases patient survival by more than a few months.
better stratify patients and identify drug targets. This sobering reality highlights the urgent need for new ALS
Development of technology platforms to interrogate hiPSC- therapeutic development, which has been plagued by high failure
derived neural cell types with relatively high-throughput will rate of drug candidates during clinical trials. This high failure
be advantageous not only for drug screening, but also for rate suggests that pre-clinical screening strategies need to be
phenotype discovery, allowing testing of multiple patient derived re-evaluated. One of the markers of disease in ALS patients is
lines, and variables, such as timing and dose response to the aberrantly low expression of neurofilament light chain (NFL) in
therapeutic agents, pathway modulators, and stress inducers. motor neurons. Further, recovery of NFL to normal levels prevents
Towards this goal, we have been working to develop platforms hallmark phenotypic changes in ALS neurons. Therefore, we
to assess fundamental aspects of neuronal morphology and wanted to establish a clinically relevant screening platform to
physiology, providing a basis for further development of more identify compounds that return expression of NFL to normal
complex phenotypic readouts and compound screens based levels in ALS patient derived motor neurons.
on patient specific hiPSC-derived neurons. We will discuss a At BrainXell, we established new technologies to rapidly
large-scale image based high-content compound screen of differentiate ALS patient induced pluripotent stem cells (iPSCs)
neuronal morphology. In addition, we will present our progress into large quantities of neurons. We then used genome editing
developing multi-electrode array (MEA) assays to monitor techniques to endogenously fuse NFL with a nanoluciferase
electrical activity, model synaptic plasticity, and evaluate drugs (NLuc) reporter, thus enabling a high-throughput screening
on networks of hiPSC-derived neurons. (HTS) system that monitors the expression levels of NFL after
72 h exposure to each compound. The assay was adapted to
Abstract Author Biography meet HTS requirements, including: large batch sizes, 1536-well
format, minimal well-to-well variation, short-term culture, plating
Dr. Anne Bang joined the Sanford Burnham Prebys Medical by automated dispenser, and low reagent volumes. Applying
Discovery Institute in June 2010 as Director of Cell Biology at a quantitative HTS approach, we screened the LOPAC, NPC,
the Conrad Prebys Center for Chemical Genomics, a state- and MIPE libraries (>6,000 compounds) in a dose dependent
of-the-art drug discovery center. Her current research efforts manner. Compounds that increase NFL expression by 50% (to
are directed at developing patient-specific, induced pluripotent approximately normal levels) were considered hits.
stem cell (iPSC)-based disease models for drug discovery, with
an emphasis on neurological and neuromuscular disease. Prior From these screens we identified 50 hit compounds that are
currently going through secondary validation. Preliminary data mTeSR™1 or TeSR™-E8™, are first exposed to a histone
looks promising. For example, one of these hits restores normal deacetylase inhibitor and then subsequently transitioned and
expression of NFL with no observed toxicity. maintained in NaïveCult™ Expansion Medium. This process is
carried out on hPSCs seeded on inactivated murine fibroblasts
In conclusion, we have developed technologies to generate
and under 5% oxygen conditions. Using our optimized protocol,
motor neurons from ALS patient iPSCs and demonstrated their
we generated multiple naïve hPSC lines (n=5) from primed
application to increase clinical relevance of high-throughput drug
human embryonic stem cell lines Shef6, H1 and H9 and human
discovery. Using this approach we can screen large libraries of
induced pluripotent stem cells WLC-1C and STiPS-F016. We
small molecules to identify hit ALS therapeutics.
also tested the ability of naïve hPSCs maintained in NaïveCult™
Expansion Medium to differentiate into endoderm, mesoderm
Abstract Author Biography and ectoderm by using the STEMdiff™ Definitive Endoderm
Kit, STEMdiff™ Mesodermal Induction Medium and STEMdiff™
Paul Guyett is a Postdoctoral Scientist at BrainXell in Madison
Neural Induction Medium kits, respectively.
Wisconsin. He graduated from Washington State University
in 2011 with a Ph.D. in Molecular Biosciences studying the During the transition to naïve hPSCs, early passage colonies
biophysical contributions of hydrophobic amino acids to undergo robust morphological changes characterized by
heterodimeric protein folding. Paul then worked with Kojo Mensa- the acquisition of a domed phase-bright morphology on a
Wilmot at University of Georgia using genetics and chemical background of heterogeneous cellular differentiation. By passage
biology to investigate protein kinase signaling pathways in the 5, cultures become increasingly homogenous with colonies
parasitic African Trypanosome. This work was then translated typically demonstrating uniform domed and phase-bright
into a thriving academic drug discovery program. Paul was morphology and low levels of background differentiation. Naïve
then recruited by BrainXell to progress their ALS drug discovery hPSC lines, in addition to displaying a naïve cellular phenotype,
program. Paul’s interests are multidisciplinary, and center on the also demonstrate the expected signature gene expression
use of small-molecules to perturb biological systems as both profiles associated with naïve pluripotency. Our results
scientific tools and potential therapeutics. demonstrate that these cells are capable of differentiation to all
somatic cell lineages with optimal results following a minimum
of 21 days of re-priming in TeSR™-E8™ or mTeSR™1.
Chemical-induction and Maintenance of
In summary, we have demonstrated robust establishment and
Naïve-Like Human Pluripotent Stem Cells expansion of chemically-induced and maintained naïve hPSCs
using NaïveCult™ Induction Kit and Expansion Medium.

KIMBERLY SNYDER
STEMCELL Technologies Inc. Kimberly Snyder obtained her Master of Science in Experimental
Vancouver, Canada Medicine at the University of British Columbia in 2014. She
completed her studies under the supervision of Dr. Kelly
McNagny studying the role of the CD34-related sialomucin,
podocalyxin in metastatic breast cancer. Furthermore, in
Human pluripotent stem cells (hPSCs) are traditionally captured a collaboration with the Centre for Drug Research and
in a primed pluripotent state when isolated from early-stage Development (CDRD), She used pre-clinical mouse models to
embryos. Human naïve cells have been previously obtained evaluate candidate therapeutic antibodies against podocalyxin
by overexpression of transcription factors regulating key to block the growth and metastasis of established tumors. In
pathways controlling pluripotency. Here we demonstrate how 2014, Kim was recruited to STEMCELL Technologies Inc. and is
the NaïveCult™-t2iLGö media system uses chemical inhibitors a Scientist in R&D working in the Pluripotent Stem Cell Biology
of histone acetyltransferases in combination with Wnt signalling Team. In her role, Kim primarily works on media development
modulators and small molecule inhibitors of mitogen-activated for the reversion and maintenance of primed human pluripotent
protein kinase kinase (MEK) and protein kinase C (PKC) to induce stem cells to the naive-like state.
hPSCs to adopt a naive-like state. Further, this media system
was developed to support the continuous robust expansion of
naïve-like hPSCs.
Chemical generation of naïve hPSCs using NaïveCult™ Induction
Kit involves sequential steps in which hPSCs, maintained in
ICBS 2018
Synthetic Chemistry
New Reactivity, New Structures...New New Strategies for Synthesizing Bioactive
Functions? Alkaloids
DAVID LUPTON DAWEI MA

Monash University Shanghai Institute of Organic Chemistry
Melbourne, Australia Shanghai, China
Discoveries in chemical synthesis often provide access to new In this lecture we report our recent efforts toward the total
materials, or previously inaccessible due to inefficiencies in synthesis of alkaloid by developing new synthetic strategies,
chemical synthesis. This pipeline, connecting novel molecular which include total syntheses zaitine and navirine C by using a
structures to discoveries in application focused chemistry, chelation-triggered conjugate addition to a,b-unsaturated nitrile
will remain integral in the future as increasingly challenging and oxidative-dearomatization/Diels-Alder cycloaddition as the
problems in, for example, energy and health, demand viable key steps; a short and convergent route for assembling gelsedine
universal solutions. alkaloids, and total synthesis of lipidilectine B by installing
its spiro indoline and lactone units through a manganese(III)-
Studies in my research group are focused around the discovery
mediated oxidative cyclization of a 1,2,3-trisubstituted indole.
and use of catalytic reactions to deliver novel molecular
structures. In this talk a summary of recent discoveries in
organocatalysis,1 transition metal catalysis,2 and biocatalysis3will Abstract Author Biography
be provided focusing on the ways that new synthesis can
Dr. Dawei Ma received his PhD in 1989 from Shanghai Institute
address unmet challenges in society.
of Organic Chemistry (SIOC), and did his postdoctoral studies
at the University of Pittsburgh and Mayo Clinic. He returned
Abstract Author Biography to SIOC in 1994, and was appointed as research professor
in 1995. He is presently the deputy director of SIOC and an
David W. Lupton graduated with a Bachelor of Science (Honors,
associate editor of Journal of Organic Chemistry. His research
1st class) in 2001 (University of Adelaide) before being awarded
interests currently focus on the development of new synthetic
a Doctorate of Philosophy for studies under the supervision
methodologies, the total synthesis of complex natural products
of Professor Martin G. Banwell (Australian National University)
and their SAR and action mode studies, as well as the discovery
in 2005. Dr. Lupton then undertook a postdoctoral fellowship
of small modulators for target proteins and special biological
with Professor Barry M. Trost (Stanford University, USA) as a Sir
processes.
Keith Murdochfellow of the American Australian Association.
In 2007 he returned to Australia to take up an academic
appointment at Monash University in Melbourne , receiving
an Australian Research Council Future Fellowship in 2011. In
addition, in 2010 he received the Athel Beckwith Lectureship
of the Royal Australian Chemical Institute (RACI), and in 2012 a
Thieme journal award of the Organic Editorial Board. In 2013 he
received the Rennie Medal of the RACI. In 2015 he received the
Alexander von Humboldt Ludwig-Leichardt Awardee for studies
with Professor Herbert Mayr. He has served as the Associate
Head of Research within the School of Chemistry and was
promoted to Professor in 2018.
Development and Application of Tyrosine Abstract Author Biography

Click Reaction Shinichi Sato received his B. Sc. Degree in 2006 from Meiji
Pharmaceutical University, and his Ph. D. degree in 2011 form
University of Tokyo (Professor Yuichi Hashimoto). He spent
one year in Professor Carlos F. Barbas’s group at The Scripps
Research Institute as a JSPS fellow. He joined the Department
SHINICHI SATO
Tokyo Institute of Technology of Chemistry, Faculty of Science, Gakushuin University as
Kanagawa, Japan an assistant professor in 2012. He is currently an assistant
professor in Laboratory for Chemistry and Life Science, Institute
of Innovative Research, Tokyo Institute of Technology. He was
awarded in Ajinomoto Award in Synthetic Organic Chemistry
and The Pharmaceutical Society of Japan Kanto Branch Young
The chemical modification of proteins with synthetic probes is an
Scientist Award.
important technique in chemical biology, protein-based therapy,
and material science. In addition to conventional modification
methods that target nucleophilic amino acid residues such Chemical Synthesis of Membrane Protein:
as lysine and cysteine residues, alternative methods that
Mirror-image Influenza A Virus Proton
can modify other amino acid residues, such as tyrosine or
tryptophan residues, have attracted immense attention recently. Channel M2 with Channel Activity
In the attempt to modify native proteins, we developed tyrosine-
specific bioconjugation reaction.
Based on the report by Barbas et al. (JACS 2010) in which
JI-SHEN ZHENG
diazodicarboxyamide compound modifies tyrosine via ene- University of Science and Technology of
type reaction, we thought that a reactive diazodicarboxyamide China
would enable us to modify the tyrosine residue efficiently. In Hefei, China
order to generate highly reactive diazodicarboxyamide in situ,
we synthesized several hydrazide derivatives (CO-NH-NH-
CO), the precursors of diazodicarboxyamide (CO-N=N-CO),
and evaluated as the tyrosine modifier using various catalysts, Lives on the earth are composed of homochiral molecules of
including peroxidase, in the presence of a tyrosine-containing L-amino acids and D-ribose nucleic acids. Reconstruction of a
peptide. The optimized reaction conditions by the peptide primitive mirror-image cell would strengthen our understanding
experiments were applied to the protein chemical modification. about the origin of life’s chirality and also have a plenty of vast
In order to clarify the modified residues on the protein, enzymatic application prospects in materials, energy and pharmaceutical
digestion of the modified protein with trypsin and LC-MS and sciences. To achieve this, one of important tasks is the
MS/MS analyses were carried out. reconstitution of the correct structure and function of the key
protein components in the mirror-image cell system. Several
We found that the N-methylated luminol derivative was activated
significant efforts on D-type enzymes and protein folding have
by horseradish peroxidase (HRP), efficiently inducing covalent
been conducted, such as mirror-image HIV-1 protease, mirror-
bond formation with tyrosine residue.
image African swine fever virus polymerase X, thermostable
This labeling reaction selectively proceeded only at a tyrosine d-polymerase thermostable Sulfolobus solfataricus P2 DNA
residue among all natural amino acid residues. Furthermore, the polymerase IV, and mirror-image D-DapA (a chaperone-
surface-exposed tyrosine residues underwent modification with dependent protein). Those pioneering work on water-soluble
N-methylated luminol derivative more efficiently than internal mirror-image proteins open a window for studies of mirror-
tyrosine residues. image lives. However, the hydrophobic mirror-image membrane
proteins for ion transportation properties are still unknown.
We found that the N-methylated luminol derivative was
efficiently activated by HRP to induce covalent bond formation Peptides were prepared by 9-fluorenylmethoxy-carbonyl solid-
with a tyrosine residue. This highly efficient tyrosine-specific phase peptide synthesis (Fmoc SPPS).
modification method with high provides an attractive strategy
The ligation of peptides was performed using the protocol of
not only for the modification of peptides but also for protein
hydrazide based native chemical ligation.
modification and immobilization.
The single channel conductivity experiments were carried out
ICBS 2018
using the instrument of Ionovation Compact. Abstract Author Biography

The mirror-image M2 ion channel (D-M2) of influenza A virus was I received my bachelor degree and doctor degree at University of
synthesized by the combination of two techniques of removable Science and Technology of China. And then I entered Tsinghua
backbone modification (RBM) strategy and native chemical University for postdoctoral research in 2012. After that, I worked
ligation of peptide hydrazide. D-M2 acted as a proton-conducting as an associate professor at the Center for Strong Magnetic
channel similar as the native L-M2, which is demonstrated by Field of the Chinese Academy of Sciences form 2014-2016.
the electrophysiological experiments. Furthermore, the channel Since 2016, I works at the University of Science and Technology
activity of D-M2 can be inhibited by anti-influenza drugs achiral of China as a professor.
amantadine and chiral R-rimantadine, but with slower kinetics
than L-M2 channel. My research focuses on the chemical synthesis of membrane
proteins, a historic challenge in the field of protein chemistry.
In summary, we totally chemically synthesized D-M2 proteins We developed the reversible backbone modification strategy for
using the RBM strategy and peptide hydrazide-based native the chemical synthesis of membrane proteins. Using the new
chemical ligation. The chemically synthesized D-M2 proteins practical strategy, we achieved the functional reconstitution of
were reconstituted in lipid bilayers. We anticipate that the the influenza A virus ion channel M2, small multidrug resistance
further investigation of the chemically synthesized other D-type protein, the site-specific isotope-labelling membrane protein
transmembrane ion channels (such as proton, sodium (Nav), probe and two-photon photo-caged protein probes.
potassium (Kv) or calcium (Cav) channels), in combination with
other looking-glass versions of biochemical processes, could
enable the reconstutition of mirror-image cells as powerful tools
for materials science and pharmaceutical research.
Notes
Chemical Proteomics for Drug Target Engagement

and Identification
Elucidating PARP Inhibitor Selectivity Using Abstract Author Biography
a PARP Family Affinity Matrix Andrew Zhang is an Associate Principal Scientist in the Chemical
Biology Group at AstraZeneca. He joined AstraZeneca in 2013
with research interests in target deconvolution, particularly using
chemical proteomics and orthogonal methods for identifying
targets, profiling selectivity, and confirming engagement.
ANDREW ZHANG
AstraZeneca Previously, he has conducted research at the interface
Boston, United States between small molecules and antibodies, on small molecule
immunomodulators as well as antibody-drug conjugates. He
obtained a Bachelors of Science degree in Chemistry and a
Bachelors of Arts degree in Molecular and Cell Biology from
the University of California, Berkeley, and completed his PhD
The poly(ADP-ribose) polymerase (PARP) family consists of
training with Professor David Spiegel at Yale University. Prior to
enzymes implicated in DNA damage response (DDR), and
joining AstraZeneca, he spent one year in the Drug Discovery
PARP inhibitors have seen widespread clinical application for
Program at the Ontario Institute for Cancer Research (Toronto,
cancers presenting deficiencies in homologous recombination.
Canada) as a postdoctoral fellow.
Identification of a comprehensive profile of targets inhibited
by PARP inhibitors, particularly understanding their pan-
PARP selectivity, is important generating hypotheses around Applying Chemical Biology in the T790M-
differences in efficacy and toxicity. Immobilized chemical EGFR Program
probes, including family affinity matrices, are very useful for
probing target engagement and selectivity in a biologically
relevant setting.
We generated an affinity matrix consisting a single promiscuous SHERRY L NIESSEN
phthalazinone analogue capable of enriching up to 15 of the Pfizer
17 known PARP enzymes, including those implicated in DDR La Jolla, United States
(PARPs 1-3) and gut toxicity (Tankyrase).
Through reverse competition of PARPs binding in MDA-
MB-436 BRCA-mutant lysate against the affinity matrix followed
by a mass spectrometry-based readout, we profiled 5 clinical To enable a more complete understanding into the mechanism
inhibitors (niraparib, olaparib, rucaparib, talazoparib, veliparib), of action of covalent EGFR inhibitors we specifically explore
showing their distinct PARP selectivity profiles in a disease the proteome-wide reactivity of a series of third-generation
relevant context. In-depth statistical analysis of dose response T790M-EGFR inhibitors in human cancer cells and animal
profiles performed with our in-house developed tool named models through the development and application of chemical
DOSCHEDA (Downstream Chemoproteomics Data Analysis) probes and quantitative mass spectrometry-based proteomic
identified putative binding partners and their interactions with methods. We identify that each T790M-EGFR inhibitor has
PARP1. a distinct off-target labeling profile in cancer cells which is
We have developed a chemical proteomics assay to profile the centered on the engagement of proteins with functional and
selectivity of PARP inhibitors in biologically relevant settings ligandable cysteines. These studies highlight the importance
across the PARP family and applied this towards understanding of performing global analyses of drug action in living systems
the pan-PARP selectivity of clinically relevant PARP inhibitors, to identify targets and off-targets that may impact efficacy and
generating hypotheses around their observed phenotypes in safety.
vitro and in vivo.
ICBS 2018
Abstract Author Biography of small molecules that direct the machinery of the ubiquitin-
proteasome system to selectively degrade disease-relevant
Sherry Niessen obtained her PhD at Scripps Research Institute proteins for therapeutic benefit.
(TSRI) in the lab of Dr. Benjamin Cravatt, and remained as a
Scipps staff scientist at The Center for Physiological Proteomics Before joining C4 Therapeutics, Andy was Senior Director,
prior to joining Pfizer in 2012 where she is currently a Principal Center for Development of Therapeutics at the Broad Institute
scientist, Worldwide Medicinal Chemistry. Sherry is a chemical of MIT and Harvard, where he led overall therapeutic efforts
biologist with 12 years of interdisciplinary research experience and provided strategic leadership for a number of major
bridging chemical biology, proteomics (applying; LTQ, Orbitrap, partnerships. Previously, he was a Full Professor of Chemistry
Velos, QE), metabolomics (applying; QQQ, qTOF), cell and at Yale University, where he received the ACS Cope Scholar
molecular biology. Award for his research accomplishments, which included
the development of small molecules aimed at modulating
Sherry’s research is currently focused on the identification ‘undruggable’ targets. Prior to this, he was a Full Professor
and characterization of therapeutic protein targets of small of Chemistry and Biochemistry at the University of Colorado
molecules. at Boulder, where his efforts in complex molecule synthesis
Education: 2005-2008 The Scripps Research Institute (TSRI), and targeting protein-protein interactions garnered a number
La Jolla, USA Ph.D. in Cell Biology and Chemical Physiology of awards, including an Alfred P. Sloan Research Fellowship,
Laboratory of Dr. Benjamin Cravatt 2000-2004 McGill an Eli Lilly Grantee Award, and a National Science Foundation
University, Montreal, Canada M.Sc. in Experimental Medicine CAREER Award. Andy received a B.Sc. (Hons) in biochemistry
Laboratory of Dr. Guy Sauvageau 1995-2000 Simon Fraser and a Ph.D. in biochemistry and chemistry from the University
University, Burnaby, Canada B.S. in Biochemistry Positions: of Canterbury in New Zealand and completed a postdoctoral
Pfizer Principal scientist (R5), Worldwide Medicinal Chemistry, fellowship in organic chemistry at the University of Pittsburgh.
La Jolla (2012-current). The Scripps Research Institute 1) Staff
Scientist, The Center for Physiological Proteomics (CPP) (2008- Bioorthogonal Chemical Probes to
2012).
Interrogate Protein Acetylation
Targeted Protein Degradation: Tools
for Target Evaluation and Therapeutic
Applications Y. GEORGE ZHENG
University of Georgia
Athens, United States
ANDREW J. PHILLIPS
C4 Therapeutics
Watertown, United States Acetylation of lysine residues is one of the most important
posttranslational modifications that diversify protein functions
by changing protein stability, location, and protein-protein
interaction. This process is mediated by Lysine acetyltransferases
(KATs). Although housands of acetylated lysine residues have
This talk will provide a brief introduction to targeted protein identified, there is a missing link connecting the compositions
degradation and will highlight two specific applications of of the cellular acetylome networks to the enzymatic activities
this rapidly emerging technology: the degradation of BET of different KAT members. The outstanding challenge is how to
bromodomain proteins for therapeutic impact in leukemias and dissect the subacetylomes of individual KATs and address their
the introduction of ATAG – an ‘open-source’ toolkit designed functions on the proteomic scale.
to enable the chemical biology community to evaluate the
degradation of targets both in vitro and in vivo. We have explored a bioorthogonal profiling of protein acetylation
strategy to label substrates of KAT enzymes. In this strategy,
engineered KAT enzymes were created in conjugation with
Abstract Author Biography matching synthetic acetyl-CoA molecules to form orthogonal
Andy Phillips is President and Chief Executive Officer of C4 labeling pairs for KAT substrate labeling, identification, and
Therapeutics, a biotech company that is developing a new class profiling.
A suite of Ac-CoA analogs containing either alkynyl or azido We have created a bioorthogonal, chemoproteomic strategy
functional group (e.g. 3AZ-CoA, 4AZ-CoA, 4PY-CoA, 5HY-CoA, to investigate KAT biology which provides a powerful enabling
6HY-CoA) were synthesized as potential cofactor surrogate for technology for activity-based lysine acylation profiling on
selective labeling of KAT substrates. Meanwhile, the active site proteomic scale. Our KAT activity profiling demonstrates
of the KATs was engineered in order to expand the cofactor extensive engagement of KATs in cellular pathways and provides
binding capability of the enzymes to accommodate the bulkier new molecular insights into understanding their functions in
synthetic cofactors. Biochemical screening was conducted to biological processes.
identify matching KAT-cofactor pairs to efficiently label protein
and peptide substrates of KATs with alkyne or azide warhead. Abstract Author Biography
We found out that several GCN5 mutant forms exhibited
appreciable activities to the synthetic cofactors. MOF-I317A Y. George Zheng received his B.S. in chemistry at Peking
was active toward all the Ac-CoA analogs. No mutation is University, Ph.D. at University of Miami, and postdoctoral training
needed as the wild-type p300 exhibited robust activity to 4PY- at Johns Hopkins University School of Medicine. From 2006 to
CoA and 3AZ-CoA. The acylated substrates can be selectively 2013, He was an Assistant Professor and Associate Professor
linked through the copper-catalyzed azide-alkyne cycloaddition in the Department of Chemistry at Georgia State University.
(CuAAC) reaction with fluorescent reporter or biotin affinity tag Since 2013, he has been an Associate Professor and Professor
for optical imaging or protein enrichment on streptavidin-coated in the Department of Pharmaceutical & Biomedical Sciences
resin. We have successfully used this bioorthogonal technology at University of Georgia. His research interest is on developing
to profile substrates of p300 and GCN5 in the context of chemical probes and drug leads to target epigenetic enzymes.
complex cellular proteomes.
Notes
ICBS 2018
Biosensors and Imaging

A Suite of New Fluorescent Biosensors for New Colours and Applications of
Dynamic Visualization of Cell Signaling in Genetically Encoded Biosensors to Probe
Living Cells Cell Signaling
JIN ZHANG ROBERT CAMPBELL

University of Alberta and The University
University of California, San Diego
of Tokyo
San Diego, United States
Edmonton, Canada
I will discuss development and application of a suite of new The advent of optogenetic tools, broadly defined here as both
fluorescent biosensors for visualizing signaling activties in living actuators for cell control and indicators for cell visualization,
cells. has revolutionized our ability to spy on the otherwise invisible
world of neuronal activities. The most versatile class of
Abstract Author Biography optogenetic indicators are the Ca2+ indicators that change
their fluorescence intensity or color in response to intracellular
Jin Zhang received her PhD in Chemistry from the U. Chicago. signaling events. These indicators are frequently used in
After completing her postdoctoral work, she joined the faculty combination with optogenetic actuators to enable simultaneous
of Johns Hopkins University School of Medicine in 2003. She control and visualization of cellular signalling with precise spatial
was promoted to Professor of Pharmacology, Neuroscience and temporal resolution. However, a persistent challenge in
and Oncology in 2013. In 2015 she moved to University this area is achieving sufficient spectral separation between
of California, San Diego as a Professor of Pharmacology, the wavelengths of light required to excite the actuator and the
Biochemistry and Bioengineering. Research in her lab focuses indicator. In this seminar I will describe our most recent efforts
on developing enabling technologies to probe the active to use protein engineering to make highly red-shifted genetically
molecules in their native environment and characterizing how encoded Ca2+ indicators that are suitable for use in combination
these active molecules change in diseases including cancer. with blue-light activatable optogenetic actuators. In addition, I
Professor Zhang is a recipient of the NIH Director’s Pioneer will discuss recent progress to develop new application of our
Award (2009), the John J. Abel Award in Pharmacology from blue-light photocleavable optogenetic actuator, PhoCl.
ASPET (2012), the Pfizer Award in Enzyme Chemistry from ACS
(2012), and NCI Outstanding Investigator Award (2015). She Abstract Author Biography
was elected as a Fellow of the AAAS in 2014. She serves on
the editorial advisory board of Cell Chemical Biology and is the Dr. Robert E. Campbell is a Professor in the Department of
Secretary/Treasurer of ASPET. Chemistry, University of Alberta (2003 - present). As of July 2018
he has a 50% appointment as Professor in the Department of
Chemistry at the The University of Tokyo, and 50% appointment
at the University of Alberta. He earned his Ph.D. in Chemistry
with Martin Tanner at the University of British Columbia in
2000 and undertook postdoctoral research at the University of
California San Diego in the lab of the late Roger Y. Tsien (2008
Nobel Prize). He is a leading developer of optogenetic tools,
including red fluorescent Ca2+ indicators used in labs around
the world. He has distributed >5000 samples of optogenetic
tools through the Addgene plasmid repository and many others
are distributed as viral vectors. Recent recognitions include a
Stanford Neurosciences Institute Visiting Scholar Award (2017), Abstract Author Biography
the Teva Canada Limited Biological and Medicinal Chemistry
Award (2016), the Rutherford Memorial Medal from the Royal Dr. Ellen Sletten is an Assistant Professor in the Department
Society of Canada (2015), and the Boehringer Ingelheim of Chemistry and Biochemistry at UCLA. She obtained her
Research Excellence Award (2014). He has multiple patents B.S. in Chemistry from Stonehill College in 2006 and PhD
awarded or pending. in Chemistry from UC Berkeley in 2011. Her thesis work
was performed in Dr. Carolyn Bertozzi’s laboratory on the
development of bioorthogonal chemistries. Upon graduation,
Shortwave Infrared Fluorophores for Dr. Sletten moved to Massachusetts Institute of Technology
Illuminating Biological Processes In Vivo as an NIH postdoctoral fellow in Dr. Timothy Swager’s group
exploring dynamic fluorescence-based sensors. In 2015, Dr.
Sletten began her independent career at UCLA, where she has
established an interdisciplinary research program that leverages
the tools of physical organic chemistry to create new optical
ELLEN M. SLETTEN chemical tools and theranostic technologies.
UCLA
Los Angeles, United States
Selectivity Differences Between Cellular
and Biochemical Analysis
Chemical biologists have created a plethora of fluorescent
probes that allow biological processes to be studied in real time.
These methods have been exceedingly successful in cells and
transparent organisms, but are less effective in higher mammals PONCHO MEISENHEIMER
Promega Biosciences
due to the limited penetration of light through tissue.
San Luis Obispo, United States
Recently, the shortwave infrared (SWIR) region of the
electromagnetic spectrum has emerged as the premier region
for optical imaging in mammals; however, there are limited
fluorophores for use at SWIR wavelengths. Our group develops Quantitative assessment of kinase target occupancy in live cells,
new fluorophores for the SWIR region of the electromagnetic under a thermodynamic equilibrium with the drug molecule,
spectrum. We focus on polymethine dyes and modify the better reflects drug affinity under physiologically relevant local
heterocycles to tune the absorption, emission, absorption ATP concentrations. Here we report the application of an
coefficient, quantum yield, and solubility of the fluorophores. energy transfer technique (NanoBRET) that enables the first
We have found that polymethine dyes with dimethylamino quantitative approach to profile target occupancy, compound
flavylium heterocycles display significantly red-shifted affinity, and residence time for a broad spectrum of intracellular
absorption and emission compared to traditional indolene- kinase enzymes. Using this technique, target occupancy data
containing polymethine dyes (cyanine dyes). The dimethylamino correlates quantitatively with traditional intracellular activity/
flavylium heptamethine dye, deemed Flav7, emits at 1045 nm pathway analysis readouts. This method allows for broad-
with quantum yield of ~ 0.6%, which is larger than commercially spectrum profiling of inhibitor selectivity against nearly 300
available SWIR polymethine fluorophores. We have prepared kinases, in a simple work-flow. We performed a systematic
micelle formulations of Flav7 and obtained high-resolution comparison of kinase inhibitor selectivity in live cells versus
optical images in mice. Additional work has surrounded biochemical analyses. Compared to published biochemical
modification of the dimethylamino flavylium heterocycles profiling results, we observed an improved intracellular
leading to enhanced photophysical properties and improved selectivity profile for certain clinically-relevant multi-kinase
nanomaterial formulations. inhibitors. Moreover, this technique allowed for a mechanistic
interrogation of micro-environmental ATP levels on engagement
The SWIR region of the electromagnetic spectrum allows
potency. When performed in real time, this technique enables
for optical imaging in animals with superior resolution and/or
a readout of compound residence time further supporting the
depth penetration as compared to the visible and near infrared
quantitative nature of this occupancy measurement. When
regions. The development of polymethine fluorophores for the
target engagement analysis is performed under equilibrium and
SWIR region will facilitate the extension of optical chemical
non-equilibrium conditions, surprising kinetic selectivity profiles
biology tools to mammals.
are observed for certain clinically-relevant kinase inhibitors.
ICBS 2018
Abstract Author Biography DNA analysis, polymer development to enable capillary

electrophoresis, and magnetic microparticle development to
As Director of Chemistry Research for Promega, Poncho enable automated genomics.
has long focused on live cell detection of the interactions
He serves on the Scientific Advisory Board for the Usona Institute
between endogenous and exogenous molecules. This group
and for the Chemical Probes Portal, and has currently co-
develops intracellular pro-luminescent probes for enzyme and
authored over 30 journal articles/reviews and is an inventor for
biomolecule detection, fluorescent tracers for energy transfer
29 issued patents and 81 pending patent applications. Poncho
target engagement assays, novel fluorescent dye development,
received his Ph.D. in Organic Synthesis at University of Colorado–
novel bioluminescent substrates, and live cell selective protein
Boulder and served on the faculty at California Polytechnic State
labels.
University–SLO prior to joining Promega Corporation in 2001.
Additionally, Poncho has lead chemistry research programs in
drug development to enable drug assisted psychotherapies,
fluorescent amidite development to enable forensic
Notes
7th Annual Conference | September 24-27, 2018 | Vancouver, Canada ICBS 2018
ICBS 2018 Rising Stars Sponsored by ACS Chemical Biology
Rising Stars
To advance the career development of young investigators in increase O-GlcNAc levels in live cells. Fusion of the nanobody
chemical biology, ICBS has established a special session at to full-length OGT(13), possessing 13 tetratricopeptide repeats
the Annual Meeting to showcase up-and-coming chemical (TPRs), or a truncated OGT(4), possessing 4 TPRs, displayed
biology scientists. The selected recipients will give a podium analogous glycosyltransferase activity in cells. Proximity-induced
presentation during the special “Rising Stars” session, and glycosylation was demonstrated on ten nucleocytoplasmic
each will be further recognized for their achievements with a proteins representing the broad array of substrates for OGT.
certificate and a monetary award. Isotope targeted glycoproteomics (IsoTaG) was used to map
specific glycosites yielded by proximity-induced glycosylation.
Proximity-Directed O-GlcNAc Transferase In all evaluated target proteins, co-transfection with nanobody-
OGT(13) or nanobody-OGT(4) increased O-GlcNAc stoichiometry
for Protein-specific O-GlcNAcylation on the target protein. Evaluation of the effect of O-GlcNAc on
some target proteins revealed altered subcellular localization. The
changes in subcellular localization was attributed to increasing
O-GlcNAc stoichiometry and scaffolding functions from OGT
CHRISTINA WOO itself.
Harvard University We report the ability to induce O-GlcNAc to specific proteins
Cambridge, United States
in live cells through introduction of an orthogonal, defined
nanobody domain to OGT. The nanobody domain can replace
part of the TPR domain, resulting in reduced innate substrate
recognition through the TPR domain and generated more
Over 15% of the cellular proteome is modified by O-linked N-acetyl selective constructs that increase O-GlcNAc levels on a range
glucosamine (O-GlcNAc), a post-translational modification of nucleocytoplasmic proteins. Manipulation of O-GlcNAc
that consists of a single glucosamine monosaccharide stoichiometry using proximity-directed OGT will catalyze
attached to serine or threonine residues of nuclear, cytosolic additional discoveries of functions for O-GlcNAc and OGT itself.
and mitochondrial proteins. Due to the ubiquitous nature of
the modification, O-GlcNAc has been implicated in numerous Abstract Author Biography
biological processes, including immune response, cancer
progression, neurodegeneration, and diabetes. Despite a Christina M. Woo obtained a BA in Chemistry from Wellesley
number of studies that point to the critical biological impact College (2008) and obtained her PhD in 2013 from Yale
of O-GlcNAc on specific proteins, delineation of the function University under the guidance of Professor Seth B. Herzon.
of O-GlcNAc modification on particular glycoproteins are In 2013, Christina joined the laboratory of Professor Carolyn
hindered by the inability to control O-GlcNAc stoichiometry on R. Bertozzi at the University of California Berkeley as a Jane
Coffins Child postdoctoral fellow and and Stanford University
specific proteins of interest in cells. A general method to control
as a Burroughs Wellcome Fund CASI Fellow. Christina joined
glycosylation on specific target proteins would enable the
the Department of Chemistry and Chemical Biology at Harvard
systematic evaluation of O-GlcNAc function in cells.
University as an Assistant Professor in 2016, where her group
To advance insight into the role of O-GlcNAc on specific proteins, is studying chemoproteomic signaling using chemical biology
we developed fusions of O-GlcNAc transferase (OGT) to and mass spectrometry methods to map and manipulate small
nanobodies as proximity-directing agents to a target protein and molecule protein interactions.
48
ICBS 2018
Chemoproteomics Profiling Reveals the assistant professor at Department of Chemical Biology, College
of Chemistry and Molecular Engineering, Peking University in
Anti-Steatosis Mechanism of a Natural December, 2013 and is also affiliated with Synthetic and Functional
Flavonoid Biomolecules Center (SFBC) and Peking-Tsinghua Center for Life
Sciences (CLS) as a Principal Investigator. His current research
programs focus on the development and application of multi-
disciplinary tools in chemical proteomics, biochemistry and
CHU WANG computational biology to streamline efforts in global profiling and
College of Chemistry and Molecular discovery of functional sites, post-translational modifications and
Engineering biomolecular interactions in proteomes.
Peking University, China
Decoding Protein Adp-Ribosylation

Networks in Cells Using Chemical Genetic
Hepatic steatosis, marked as excessive lipid accumulation in
hepatocytes, constitutes the early stage of non-alcoholic fatty
Approaches
liver diseases (NAFLD), a world-wide epidemic that is strongly
implicated with obesity and metabolic disorders. A natural
flavonoid compound isolated from Chinese herbal medicine
was shown with strong anti-steatosis effect, however, the MICHAEL COHEN
mechanism of action remains elusive. Oregon Health and Science University,
USA
We employed a quantitative chemical proteomic strategy to
deconvolute the protein targets of this compound. Photo-
affinity probes were synthesized, SILAC-based chemical
proteomics experiments were performed and multiple targets
were identified. ADP-ribosylation (ADPr) is a reversibleposttranslational
modification that is essential for cellular function, yet little
Guided by functional pathway analysis, we discovered that information exists regarding relevant protein substrates and
the flavonoid binds to a key enzyme in the fatty acid oxidation target specificity. ADPr is catalyzed by a family of 17 enzymes
pathway and allosterically activates the enzyme to accelerates in humans known as poly-ADP-ribose-polymerases (PARP1-16
the rate of fatty acid degradation in the liver. Oral administration in humans; also known as ARTDs), which transfer the ADP-
of the compound significantly ameliorates the symptoms ribose moiety from nicotinamide adenine dinucleotide (NAD+)
associated with diet-induced obesity and hepatic steatosis. to amino acids on target proteins. The PARP family is sub-
Our work revealed the mechanism of action of a natural flavonoid classified based on the ability of the individual PARP enzymes to
compound with unique anti-steatosis activity and suggested catalyze the transfer of a single ADP-ribose unit (mono-PARPs:
that flavonoids may serve as a common scaffold to develop PARP3, 6-8, 10-12, 14-16) or multiple ADP-ribose units (poly-
novel drugs for pharmacological treatment of NAFLD. PARPs: PARP1-2, 4, 5a, 5b) onto target proteins. Progress in
understanding the specific role of a given PARP in cells has
been severely limited by the inability to identify the direct targets
for individual PARPs in a cellular context.
Dr. Chu Wang obtained his B.S. degree in Biology from University To address this challenge, my laboratory has designed novel
of Science and Technology of China (USTC) in 2001 and his orthogonal NAD+analog-engineered PARP pairs for the
Ph.D. degree with Professor David Baker in 2007 from University identification of direct protein targets of individual PARPs. The
of Washington. He did his postdoctoral training with Professor orthogonal NAD+ analog contains a benzyl group at the C-5
Benjamin F. Cravatt at The Scripps Research Institute from position of the nicotinamide ring, which interacts with a hydrophobic
2009 to 2013 and was supported by NIH / NIEHS Pathways to pocket uniquely found in the engineered PARPs, and an alkyne
Independence (K99/R00) postdoctoral award. He started as an tag at the N-6 position on the adenosine ring for copper-catalyzed
49
conjugation to a biotin−azide probe. We have successfully applied Abstract Author Biography

our chemical genetic approach toward the identification of the
direct targets of the poly-PARP subfamily, and have recently Michael Cohen received his B.S. in Chemistry from University
extended this strategy to the mono-PARP subfamily. of California, Irvine. His interest in the chemistry and biology
interface led him to pursue a Ph.D. in Chemistry and Chemical
I will discuss our unpublished work on identifying the direct Biology at the University of California, San Francisco under
targets of the mono-PARP, PARP14. PARP14 is involved in the supervision of Jack Taunton. In his graduate studies, he
normal immune function through the IL-4 signaling pathway and developed structural bioinformatics-based approaches for
is a pro-survival factor in multiple myeloma and hepatocellular generating selective protein kinase inhibitors. He then pursued
carcinoma. Combining our chemical genetics approach postdoctoral studies with Samie Jaffrey at Cornell Medical
with a BioID approach for proximity-dependent labeling of College where he investigated compartmentalized NAD+
PARP14 interactors, we identified 114 PARP14-specific protein biosynthesis. In 2011, he began his independent career at
substrates, several of which are RNA regulatory proteins. One Oregon Health and Science University where his lab is focused
of these targets is PARP13, a protein known to play a role in on using chemistry-based approaches to investigate NAD+
regulating RNA stability. PARP14 MARylates PARP13 on several signaling. His lab is particularly interested in enzymes known
acidic amino acids. as PARPs, which are the major consumers of NAD+ in the cell
This study not only reveals crosstalk among PARP family and mediate post-translational modification known as ADP-
members but also highlights the advantage of using disparate ribosylation. Over the last several years, his lab has developed
approaches for identifying the direct targets of individual PARP novel chemical tools which have revealed new roles for PARPs
family members. and ADP-ribosylation in cells.
Past Rising Stars

2017 2015 2013
Toru Komatsu Alessio Ciulli Bradley L. Pentelute,
University of Tokyo University of Dundee, UK Massachusetts Institute of Technology
Qi Zhang Edward Lemke Christian Ottmann,
Fudan University EMBL, Germany Eindhoven University of Technology,
Haitao Zhang Evan Miller Netherlands
Zhejiang University University of California Berkley Xiaoguang Lei,
National Institute of Biological Sciences,
China
2016 2014
Yimon Aye Evripidis Gavathiotis
Cornell University Albert Einstein College of Medicine
Ratmir Dedra Kenjiro Hanaoka
University of Alberta University of Tokyo
William Pomerantz Jiaoyang Jiang
University of Minnesota University of Wisconsin-Madison
50
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ICBS 2018
Poster Presenters
Board
Presenter Poster Title Category
Number
DIRECT FLUORESCENT LABELING OF O-GLCNAC MODIFIED PROTEINS IN LIVE CELLS
Hong Yee Tan P-02 Glycobiology
USING METABOLIC INTERMEDIATES AS PRECURSORS
A NOVEL MECHANISM BASED APPROACH FOR SCREENING METAGENOMIC LIBRARIES
Seyed Nasseri P-03 Glycobiology
FOR UNUSAUL GLYCOSIDASES
DEVELOPMENT OF AN ACTIVATABLE PHOTOACOUSTIC PROBE FOR HYPOCHLOROUS
Takayuki Ikeno P-05 Imaging Tools
ACID
INNOVATIVE APPROACHES FOR SECURE, MODERN COLLABORATIVE DRUG
Heather Arnaiz P-07 Medicinal Chemistry
DISCOVERY
James Meinig TARGETED PRODRUGS FOR CNS-SELECTIVE DRUG DISTRIBUTION P-08 Medicinal Chemistry
ALBUMIN-BINDING PENTAFLUOROPHENYL-SULFIDE PEPTIDE MACROCYCLE WITH
Jeffrey Y.K. Wong P-09 Medicinal Chemistry
EXTENDED CIRCULATION HALF-LIFE IN VIVO
EXPLOITING CHEMICAL SYNTHETIC-LETHAL INTERACTIONS TO TARGET
Dennis Liu P-10 Natural Products Chemistry
ANTIMICROBIAL-RESISTANT PATHOGENS
A SELECTIVE GENOME-GUIDED METHOD FOR ENVIRONMENTAL BURKHOLDERIA
Fred Haeckl P-11 Natural Products Chemistry
ISOLATION
Joseph Egan USING NMR TO UNLOCK CHEMICAL DIVERSITY FROM NATURAL PRODUCT EXTRACTS P-12 Natural Products Chemistry
NATURAL PRODUCTS LIBRARY DIVERSIFICATION THROUGH CHEMICAL
Nicole LeGrow P-13 Natural Products Chemistry
TRANSFORMATION
DEVELOPMENT OF A CHEMICAL BIOLOGY SCREEN FOR INHIBITORS OF STOP-GO
Jasmine Li-Brubacher P-14 Other
TRANSLATION
IDENTIFICATION OF CYTOTOXIC, GLUTATHIONE-REACTIVE MOIETIES INDUCING
Julian Wilke P-15 Other
ACCUMULATION OF REACTIVE OXYGEN SPECIES VIA GLUTATHIONE DEPLETION
Karson Kump TARGETING MCL-1 TO OVERCOME RESISTANCE IN SOLID TUMORS P-16 Other
Thomas Garner ALLOSTERIC MODULATION AND THERAPEUTIC INHIBITION OF PRO-APOPTOTIC BAX. P-17 Other
IN PURSUIT OF SMALL MOLECULE INHIBITORS OF ETV6 PNT DOMAIN
Chloe Gerak P-19 Protein-Protein Interactions
POLYMERIZATION
PHOTOACTIVATABLE FARNESYL-ANALOGUES AS PROBES TO IDENTIFY PROTEIN-
Michael Winzker P-20 Protein-Protein Interactions
PROTEIN INTERACTIONS
Alena Istrate CYCLOPROPENONE REAGENTS FOR SITE-SELECTIVE CYSTEINE BIOCONJUGATION P-21 Synthetic Biology
Kenzo Yamatsugu SYNTHETIC HISTONE ACYLATION WITH CHEMICAL CATALYSTS P-22 Synthetic Biology
IN SEARCH FOR AN AFKDNASE INHIBITOR: A POTENTIAL THERAPEUTIC FOR TREATING
Ali Nejatie P-23 Synthetic Chemistry
INVASIVE ASPERGILLOSIS
Barbara Sohr CHEMICAL PROBES FOR INTRACELLULAR HYPOXIA TARGETING P-24 Synthetic Chemistry
PROGRAMMABLE CHEMICAL ASSEMBLY OF NON-NATURAL AMINO ACIDS USING DNA-
Charlotte Zammit P-25 Synthetic Chemistry
TEMPLATED ORGANIC SYNTHESIS
Nicole Houszka INTRACELLULAR BIOORTHOGONAL CLEAVAGE P-26 Synthetic Chemistry
DEVELOPMENT OF SMALL MOLECULE COMPOUNDS FOR TREATMENT OF PATIENTS Target Engagement/
Saiko Shibata P-27
WITH CYSTIC FIBROSIS CARRYING THE SPLICING MUTATION Mechansims
DIFFERENTIAL REGULATION OF PRO-INFLAMMATORY CYTOKINE SECRETION VIA SMALL Target Engagement/
Wansang Cho P-28
MOLECULE TARGETING RECYCLING ENDOSOMAL PROTEIN RAB11 Mechansims
A NOVEL SCENARIO OF BACTERIAL INFECTION IN PLANT: CORONATINE INDUCES
Syusuke Egoshi P-31 Natural Products Chemistry
STOMATAL OPENING THROUGH TWO DIFFERENT TARGET PROTEINS IN GUARD CELLS
CUTTING THE GLUCOSE SUPPLY OF CANCER CELLS BY MEANS OF SMALL Target Engagement/
Elena Reckzeh P-32
MOLECULES Mechansims
NEW PALLADIUM CATALYSTS FOR IN CELLULO PROBE UNCAGING: FROM THE BENCH
Mathieu Soetens P-33 Imaging Tools
TO CELLS
SELECTIVE PURIFICATION AND LABELING OF LIGAND-BINDING PROTEINS ON
Michihiko Tsushima P-35 Other
RUTHENIUM PHOTOCATALYST FUNCTIONALIZED AFFINITY BEADS
Board
Presenter Poster Title Category
Number
A CLICK PROBE-BASED APPROACH FOR VISUALIZATION OF DRUG-TARGET Target Engagement/
Anna Rutkowska-Klute P-36
INTERACTIONS AND TARGET ENGAGEMENT MEASUREMENT AT SINGLE CELL LEVEL Mechansims
AFFINITY CONTROLLED INDUCTION OF ANTIBODY-DEPENDENT CELL-MEDIATED
Koichi Sasaki P-37 Medicinal Chemistry
CYTOTOXICITY BY FC BINDING ANTIBODY RECRUITING MOLECULES
Guillaume Médard CHEMOPROTEOMICS-AIDED DRUG DISCOVERY P-38 Medicinal Chemistry
Polina Prokofeva PROTEOME-WIDE STRUCTURE-AFFINITY RELATIONSHIPS P-40 Medicinal Chemistry
50 SHADES OF KINASE INHIBITION – APPLICATIONS OF THE TARGET LANDSCAPE OF Target Engagement/
Stephanie Heinzlmeir P-41
CLINICAL KINASE DRUGS Mechansims
DEVELOPMENT OF EP2 ANTAGONISTS: FROM ASSAY DEVELOPMENT TO PRECLINICAL
Thota Ganesh P-42 Medicinal Chemistry
LEAD OPTIMIZATION.
NITRIC OXIDE DONATING RUTHENIUM(II) COMPLEXES AS ANTICANCER AND
Shireen Jozi P-43 Medicinal Chemistry
ANTIBACTERIAL AGENTS
CHEMICAL PROBE DISCOVERY TO INTERROGATE YAP-TEAD INTERACTION IN THE
Kun Qian P-45 Protein-Protein Interactions
HIPPO SIGNALING PATHWAY
Phillip Danby GLYCOSIDE HYDROLASE CATALYZED HYDROLYSIS OF NON-GLYCOSIDIC LINKAGES P-48 Glycobiology
SYNTHESIS AND APPLICATION OF A MECHANISM-BASED INACTIVATOR OF ENDO-
Namrata Jain P-52 Synthetic Chemistry
(XYLO)GLUCANASE
ANTIMYCOBACTERIAL AND CYTOTOXICITY STUDIES ON CINNAMIC ACID DERIVATIVE
Victor Fadipe P-54 Medicinal Chemistry
OF OLEANOLIC ACID AT C-28 POSITION
Amy Weeks MAPPING PROTEOLYSIS AT THE SURFACE OF LIVING CELLS P-55 Degradomics
Eline Sijbesma DISULFIDE TRAPPING FOR THE DISCOVERY OF SELECTIVE PPI MODULATORS P-56 Protein-Protein Interactions
Masayasu Toyomoto DRUG DISCOVERY BY RE-SEARCHING CANCER METABOLISM AND GPCR SIGNALING P-58 Other
Matthew Alteen CHEMICAL TOOLS FOR THE DISCOVERY OF O-GLCNAC TRANSFERASE INHIBITORS P-62 Glycobiology
INFLUENCE OF NON-NATURAL AMINO ACIDS ON THE BIOLOGICAL ACTIVITY PROFILE
Evan Haney P-63 Medicinal Chemistry
OF SYNTHETIC HOST DEFENCE PEPTIDES
Sebastian Andrei PRINCIPLES BEHIND THE STABILIZATION OF PROTEIN-PROTEIN INTERACTIONS P-64 Medicinal Chemistry
IN VITRO CHARACTERIZATION OF A CRYPTIC GENE CLUSTER ENCODING AN O2, PLP-
Jason Hedges P-65 Natural Products Chemistry
DEPENDENT OXIDASE
Cameron Murray FINDING INHIBITORS OF PNKP TO TREAT PTEN DEFICIENT CANCERS P-67 Medicinal Chemistry
LONG CIRCULATING SINGLE POLYMER NANOPARTICLES FORM A DYNAMIC PROTEIN
Lily Takeuchi P-69 Other
CORONA IN VIVO
UNPRECEDENTED TAMBJAMINE ALKALOIDS DETECTED IN THE EXTRACT OF THE
Mirelle Takaki P-70 Natural Products Chemistry
MANTLE OF THE NUDIBRANCH ROBOASTRA ERNSTI
A MULTIPLEXED QUANTITATIVE TARGET ENGAGEMENT TECHNOLOGY TO DISCOVER
AND VALIDATE THE MECHANISM OF BROAD-SPECTRUM ANTIPROTEOLYTIC
Target Engagement/
Francois Jean DRUG CANDIDATES: N-TERMINAL ACETYL (NTAC)-MRM ASSAYS TO QUANTIFY P-72
Mechansims
HOST-MEDIATED ENDOPROTEOLYTIC CLEAVAGE OF ENVELOPE GLYCOPROTEIN
PRECURSORS OF PATHOGENIC VIRUSES.
Akane Kawamura CYCLIC PEPTIDE TOOLS FOR EPIGENETIC PROTEINS P-73 Protein-Protein Interactions
TARGETED NUDT5 INHIBITORS BLOCK HORMONE SIGNALING IN BREAST
Brent Page P-74 Medicinal Chemistry
CANCER CELLS
Doug Auld INTRODUCTION TO THE FAST-LAB: NOVARTIS OPEN SPACE FOR COLLABORATIONS P-75 Other
Police
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7th Annual Conference
September 24-27, 2018
Vancouver, Canada
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7th Annual Conference

September 24-27, 2018

Towards Translational Impact

Towards Translational Impact

Local Program and Organizing Committee

ICBS Organizing Committee

ICBS Young Chemical Biologist Award 2018 Selection Committee

ICBS Board of Directors

Lixin Zhang Haian Fu Jonathan Baell

Rathnam Chaguturu Tom Pfeifer Masatoshi Hagiwara

Zaneta Nikolovska-Coleska Siddhartha Roy

ICBS International Advisory Board

Stephen Benkovic Sir Philip Cohen Jian Ding

Chris Lipinski Ferid Murad Bernard Munos

Litao Zhang Stuart Schreiber Paul Workman

Tetsuo Nagano Leonard Zon Herbert Waldmann

8:30AM – 9:00AM Coffee Playhouse Lobby

9:00AM – 9:10AM Welcome Orchestra Right & Left

11:10AM – 11:25AM Coffee Break Playhouse Lobby

12:45 PM – 1:45PM Lunch on Your Own

Tech Talks Orchestra Right & Left

Creating and Deploying Next Generation Informatics Solutions – What

3:15PM – 3:30PM Antibody-Drug Conjugates Graham Garnett, Zymeworks, Canada

3:30PM – 3:50PM Coffee Break and Exhibitor Viewing Salon A

3:50PM – 4:00 PM ICBS Conference Welcome Orchestra Right & Left

4:00PM – 4:05PM Keynote Introduction Orchestra Right & Left

Keynote – Craig M. Crews, Yale University, USA

CONFERENCE DAY 1: TUESDAY, SEPTEMBER 25, 2018

8:30AM – 9:00AM Coffee Playhouse Lobby

9:00AM – 9:15AM Welcome Orchestra Right & Left

10:30AM – 10:50AM Coffee Break and Exhibitor Viewing Salon A

Session II – Glyco Chemical Biology

12:15PM – 1:15PM Lunch on Your Own and Exhibitor Viewing Salon A

Open Panel Discussion

Session III – Computational Chemical Biology

3:15PM – 3:35PM Coffee Break and Exhibitor Viewing Salon A

Session IV - Emerging and Other Topics

CONFERENCE DAY 2: WEDNESDAY, SEPTEMBER 26, 2018

8:30AM – 9:00AM Coffee Playhouse Lobby

9:00AM – 9:05AM Conference Updates Orchestra Right & Left

Session V – The Chemical Biology – Medicinal Chemistry

10:25AM – 10:45AM Coffee Break and Exhibitor Viewing Salon A

Session VI– Synthetic Biology

12:15PM – 1:15PM Lunch on Your Own and Exhibitor Viewing

CONFERENCE DAY 2: WEDNESDAY, SEPTEMBER 26, 2018

3:10PM – 3:40PM Coffee Break and Exhibitor Viewing Salon A

CONFERENCE DAY 3: THURSDAY, SEPTEMBER 27, 2018

8:30AM – 9:00AM Coffee Playhouse Lobby

9:00AM – 09:05AM Conference Updates Orchestra Right & Left

Session VIII – Synthetic Chemistry

10:25AM – 10:45AM Coffee Break and Exhibitor Viewing Salon A

10:45AM – 10:50AM Keynote Introduction Orchestra Right & Left

Keynote - Jörn Piel, ETH Zurich, Switzerland

12:15PM – 1:15PM Lunch on Your Own and Exhibitor Viewing

Session IX – Chemical Proteomics for Drug Target Engagement

3:00PM – 3:20PM Coffee Break and Exhibitor Viewing Salon A

Session X– Biosensors and Imaging

4:50PM – 5:00PM Closing Remarks Orchestra Right & Left

PRECONFERENCE: MONDAY, SEPTEMBER 24, 2018

CONFERENCE DAY 1: TUESDAY, SEPTEMBER 25, 2018

CONFERENCE DAY 1: TUESDAY, SEPTEMBER 25, 2018

CONFERENCE DAY 2: WEDNESDAY, SEPTEMBER 26, 2018

CONFERENCE DAY 2: WEDNESDAY, SEPTEMBER 26, 2018

CONFERENCE DAY 2: WEDNESDAY, SEPTEMBER 26, 2018