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The Reference Module in Biomedical Sciences covers all aspects of this interdisciplinary area of study. This
comprehensive online Reference Module forms the definitive source for those entering, researching or
teaching in any of the many disciplines making up this area of study. In addition to a regular supply of new
articles, all previously published articles are reviewed for currency to ensure articles are up-to-date. Articles that
are determined to be current according to this review receive a timestamp that appears on the article on
ScienceDirect indicating the date of the last currency review. Articles that are determined out-of-date are
updated. These updates are completed by the original author(s) or by an Updater under the editorial
direction of the Editor-in-Chief and the Subject Editors. In this way the Reference Module provides the
assurance of up-to-date content that has been vetted by a highly qualified Editorial Board and date-stamped
to mark the date of the last review or update.
The central organizing structure for the Reference Module is a Subject Hierarchy on ScienceDirect that is used
to provide context for each article and to provide a navigational tool for users to explore the subject area. The
subject hierarchy is determined by the expert Editorial Board and technically checked by the Publisher.
Articles are written by individuals and/or groups of experts in the field under the guidance of Subject Editors
who are guided by the Editor-in-Chief. The articles are written at a level that allows upper-undergraduate
students to understand the material, while providing active researchers, whether in academia or corporations,
with an authoritative and up-to-date source of foundational reference material for all aspects of the field and its
neighboring disciplines.
The Reference Module comprises of approx. 4500 articles at launch and Elsevier anticipates anticipate
including new and updated articles on a regular basis.

Reference Module in Biomedical Research i



Michael J. Caplan is the C.N.H. Long Professor and Chair of the Department
of Cellular and Molecular Physiology and Professor of Cell Biology at the Yale
University School of Medicine. He earned his undergraduate degree from
Harvard University in 1980, and his M.D. and Ph.D. degrees from Yale
University in 1987, working in the laboratories of Drs. J.D. Jamieson and
G.E. Palade. He joined Yales Department of Cellular and Molecular
Physiology as a faculty member in 1988. He has received fellowships from
the Helen Hay Whitney Foundation, the David and Lucille Packard
Foundation for Science and Engineering and a National Young Investigator
Award from the National Science Foundation. He has received the Young
Investigator Awards from the American Physiological Society and the
American Society of Nephrologists, and has delivered the American
Physiological Societys Carl W. Gottschalk Distinguished Lectureship.
He has been elected to membership in the American Association of
Physicians and has also been very honoured to receive Yale University School of Medicines Bohmfalk Prize
for teaching and to be selected as the first recipient of Yale Universitys Award for Postdoctoral Mentorship.
His scientific work focuses on understanding the ways in which kidney cells generate and maintain their unique
structures. His laboratory also studies Autosomal Dominant Polycystic Kidney Disease, a prevalent and serious
genetic disorder and a major cause of kidney failure. The Caplan laboratory is working to understand the
mechanisms responsible for this condition and to identify targets for new therapies.


Ralph A. Bradshaw received degrees in chemistry and biochemistry from

Colby College and Duke University and research training at Indiana
University and the University of Washington. He served on the faculties of
Washington University School of Medicine (196982) and the University of
California, Irvine (19822006) and is currently Professor Emeritus at UCI and
Professor of Chemistry and Pharmaceutical Chemistry at UCSF. In addition to
membership in many learned societies, he has served as president of the
Federation of American Societies for Experimental Biology (FASEB)
(199596), treasurer of the American Society for Biochemistry and Molecular
Biology (199197) and was the founding president of the Protein Society
(198687). He has also been on a number of editorial boards, and was
Editor-in-Chief or Associate Editor of several journals, including TIBS, Protein
Science and the Journal of Biological Chemistry, and, in 2000, he founded and

ii Editor Biographies

edited Molecular and Cellular Proteomics. He has organized several dozen meetings, and been an advisor/
consultant to academia, industry and government on numerous occasions. Among other honors, he received
the Passano Foundation Young Scientist Award (1976), the gold medal of the Italian National Research
Council (CNR)(1986), the Australian Society of Medical Research Gold Medal (1999) and the HUPO
Distinguished Service Award (2010). His research interests have focused on the structure and function of
proteins, with particular attention to polypeptide growth factors, their receptors and the intracellular signals
they induce. He has published over 350 scientific articles and edited more than a dozen books.

David B. Bylund, is Professor Emeritus in the Department of Pharmacology

and Experimental Neuroscience at the University of Nebraska Medical Center
in Omaha, Nebraska, USA. He received his Ph.D. in Biochemistry in 1974 from
the University of California, Davis in the laboratory of Nobel Laureate Edwin
G. Krebs. Following postdoctoral work in the laboratory of Solomon H. Snyder
at Johns Hopkins in Baltimore, MD, he became a faculty member in the
Department Pharmacology, University of Missouri-Columbia. In 1988, he
assumed the Chair of the Department of Pharmacology at University of
Nebraska Medical Center in Omaha.
Bylund has served as the President of the American Society for Pharmacology
and Experimental Therapeutics and as a member of the Board of Directors of
the Federation of American Societies for Experimental Biology. Bylund has
been the Editor of Pharmacological Reviews and is a co-editor of xPharm, a
comprehensive, web-based database. He is included in the ISI database of
highly cited researchers in Pharmacology ( Bylund has had a long term interest in
the classification and regulation of adrenergic receptors with a current emphasis on adolescent depression. His
research activities have been well-funded by NIH and he is the author of over 200 papers.

Bruce M. Carlson is Professor Emeritus at the University of Michigan, where he spent 40 years as a faculty
member. Starting as Assistant Professor of Anatomy, he ended his academic career as Chair of the Department
of Anatomy and Cell Biology and subsequently as Director of the Institute of Gerontology. He received his BA
from Gustavus Adolphus College, an MS in ichthyology from Cornell University and an MD-PhD (anatomy)
from the University of Minnesota. His research has concentrated on limb development and regeneration,
muscle regeneration and aging, as well as the biology of long-term denervation. In addition to over
200 research articles, he has published 13 books and 15 edited books. He has received a number of major
teaching and research awards and has served as President of the American Association of Anatomists and the
Association for Anatomy, Cell Biology and Neurobiology Chairpersons. An avid fisherman, he has written
articles for a fishing magazine for 25 years, as well as a book on lake biology. In retirement, he divides his time
among directing a long-term study on fish growth, writing books and serving on foundation boards.

S. J. Enna received his B.A. degree (1965, Biology) from Rockhurst University,
Kansas City, Missouri and both his M.S. (1967, Pharmacology) and Ph.D.
(1970, Pharmacology) degrees from the University of Missouri-Kansas City.
Postdoctoral training in pharmacology was completed at the University of
Texas Southwestern Medical School in Dallas, at F. Hoffmann-La Roche in
Basel, Switzerland, and the Department of Pharmacology and Experimental
Therapeutics at Johns Hopkins University School of Medicine in Baltimore.
Enna spent 10 years on the faculty at the University of Texas Medical School at
Houston in the Departments of Pharmacology and Neurobiology. While at the
University of Texas Enna was also a consultant for ICI-USA, Inc., Merck, Sharp
and Dohme Research Laboratories, Bristol-Myers Corporation, and Panlabs,
Inc. From 1986-1990, Enna was Senior Vice President and Scientific Director
of Nova Pharmaceutical Corporation in Baltimore, and Executive Vice
Editor Biographies iii

President from 1990-1992. He is currently Associate Dean for Research and Graduate Education as well as
Professor of Physiology and of Pharmacology at the University of Kansas Medical School. Enna served as chair
of the Department of Pharmacology, Toxicology and Therapeutics at the University of Kansas Medical School
from 1992 to 2003. Other previous academic appointments include Lecturer in the Department of
Neuroscience at The Johns Hopkins University School of Medicine in Baltimore and Adjunct Professor of
Pharmacology at Tulane University School of Medicine in New Orleans.
Enna served for six years as editor of The Journal of Pharmacology and Experimental Therapeutics, and is currently
co-editor of Current Protocols in Pharmacology. He is also Editor-in-Chief of Biochemical Pharmacology, Executive
Editor-in-Chief of Pharmacology and Therapeutics and Series Editor of Advances in Pharmacology. Besides his
editorships, Enna serves on the editorial boards of Brain Research, Life Sciences and CNS Drug Reviews. He has
been the recipient of Research Career Development Awards from the National Institute of Mental Health
and the National Institute for Neurological, Communicative Disorders and Stoke. Other awards include the
John Jacob Abel Award and the Torald Sollmann Award from the American Society for Pharmacology
and Experimental Therapeutics, the Daniel H. Efron Award from the American College of
Neuropsychopharmacology, and a PhARMA Foundation Excellence Award. In recent years he has been a
member of the Scientific Advisory Council of Abbott Laboratories, has served on the Board of Directors of
the Life Sciences Research Office, and on the Scientific Advisory Board of the National Alliance for Autism
Research. He is currently a member of the Basic Pharmacology Advisory Committee of the PhARMA
Foundation. Enna has held many elective offices in professional societies including the presidency of the
American Society for Pharmacology and Experimental Therapeutics (ASPET). Since 2006 he has served as
Secretary General of the International Union of Basic and Clinical Pharmacology (IUPHAR).
Ennas research interests include neuropharmacology, neurochemistry and neuropsychiatric disorders. He has
made significant contributions in defining the pharmacological and biochemical properties of
neurotransmitter receptors, in particular those for GABA. He has also conducted research into the effects of
hormones on neurotransmitter receptor function and receptor responses to psychotherapeutics, the
development of receptor antagonists for NMDA, cholinergic muscarinic and bradykinin receptors, and the
identification of the cellular components of coincident signaling in brain. Ennas research is described in over
200 published research reports, reviews, and book chapters. He has authored or edited over three dozen books
on topics ranging from neuropharmacology in general, to neurotransmitter receptors and GABA.

Ilpo Huhtaniemi received his MD and PhD at University of Helsinki, Finland,

did postdoctoral training in USA (UC San Francisco and NIH, Bethesda), and
has been on sabbatical leave in Germany, USA and Scotland. He held
19862002 the post of Professor and Chairman of Physiology at University
of Turku, Finland. He moved in 2002 to UK to a Chair in Reproductive
Endocrinology at Imperial College London. He has received several national
and international honours, amongst them a fellowship of The Academy of
Medical Sciences (UK) and a Doctor Honoris Causa at the Medical University
Lodz, Poland, and University of Szeged, Hungary. He has been the Chief
Managing Editor of Molecular and Cellular Endocrinology since 1999, has
served in the Editorial Board of Endocrinology and Endocrine Reviews and
is/has been the Editor or Editorial Board Member of several other scientific
journals (e.g. Eur J Endocrinol, Clin Endocrinol, Hum Reprod Update, J Endocrinol,
Mol Hum Reprod, Reproduction, Asian J Androl). He has extensive experience as
Official of international scientific organizations (e.g. Past President of
International Society of Andrology). His research interests include clinical and basic reproductive
endocrinology, in particular the function of gonadotrophins and male reproductive endocrinology. He also
has long-term interests in development of male contraception, hormone-dependent cancer, and the
endocrinology of ageing. He has authored about 650 peer-reviewed research articles and reviews.
iv Editor Biographies

Shashikant Kulkarni is the Director of Cytogenomics and Molecular Pathology

at Washington University School of Medicine in St. Louis. He is an Associate
Professor in the departments of Pathology & Immunology, Pediatrics and
Genetics. He trained at Harvard Medical School, Imperial College, London UK
and at AIIMS, India. He is an ABMG Board-certified medical geneticist. In his
role, Kulkarni oversees one of the most modern CLIA certified and CAP
accredited state-of-art full-service academic cytogenomics and molecular
pathology laboratories in the country, currently staffed by over 150 board
certified pathologists, clinical genomocists, clinical bioinformaticists and
certified genetic technologists. Full spectrum of Clinical Genomic testing from
chromosomes to base-pairs spanning cytogenetics, FISH, chromosomal microarray
and NGS is performed in the laboratory. Test areas include prenatal diagnostics,
perinatal and childhood studies in the evaluation of congenital and
developmental disorders, infertility and pregnancy loss studies and cancer.
Kulkarni is actively involved in defining standards for next generation
sequencing in clinical diagnostics through his collaboration with the Centers for Disease Control and
Prevention through the Clinical Next-Generation-Sequencing Quality Standards National Working Group
and is a co-chairman of Clinical Laboratory Standards Institute (CLSI) for microarray-based clinical
diagnostics. He also serves on the Scientific Advisory Board of NIH Institute National Institute of General
Medical Sciences Coriell Institute. Kulkarni is considered an expert and key opinion leader in the field of
Clinical Genomics and Next Generation Sequencing technology and he has given numerous invited
presentations both nationally and internationally. He is on the editorial board of several peer reviewed
Kulkarni is the program director of the Clinical Genomics training program at Washington University School of
Medicine and trains residents and fellows in clinical genomics. He conducts basic research in genomics of
multiple myeloma and acute myeloid leukemia and has published extensively in peer-reviewed articles in
journals such as Cell, Nature, Nature Biotechnology, Journal of American Medical Association and New
England Journal of Medicine.

Brian Mahy was born in Guernsey in 1937 and educated at Elizabeth College,
a school founded in 1563. From there he went to the University of
Southampton from 19561962, receiving BSc and PhD degrees in
Physiology and Biochemistry, then to the University of London, where he
did postdoctoral work in virology. In 1965 he moved to the University of
Cambridge, becoming a Fellow of Wolfson College and Assistant Director of
Research in Virology in the Department of Pathology. He established a
research and teaching group on influenza and paramyxoviruses, and created
a series of internationally recognized conferences on negative strand viruses.
He received degrees of MA and ScD (based on publications) during 19 years at
Cambridge University.
He spent sabbatical years in 197374 as an Eleanor Roosevelt International
Cancer Fellow working at UC San Francisco with Nobel Laureates Bishop and
Varmus, and in 198081 as a German science fellow in the University of
Wurzburg, Germany with Volker ter Meulen. In 1984 he became Director of
the Animal Virus Research Institute (now the Pirbright Laboratory), UK, then in 1989 moved to the USA where
he became Director of the Division of Viral and Rickettsial Diseases, CDC, Atlanta. He became a charter
member of the Senior Biomedical Research Service at CDC. From 19942000 he served as Chair of the
Committee on International Policies of the American Society of Microbiology Public and Scientific Affairs
Board. From 199093 he served as Chairman of the Virology Division of the International Union of
Microbiological Societies (IUMS), then from 19941999 served as Vice-President of the IUMS, which serves
more than 100,000 members worldwide. He was elected President of the IUMS in 1999, and became Past-
President from 20022005. He was elected a Fellow of the IDSA, and a Fellow of the American Academy of
Editor Biographies v

He founded the Elsevier journal, Virus Research in 1984 and remained Editor-in-Chief until 2011. He has also
been an Editor of the Journal of Medical Virology and Reviews in Medical Virology and is currently Senior Associate
Director, Emeritus for the journal Emerging Infectious Diseases, and is Series Editor of Issues in Infectious Diseases.
He has published 36 books, and over 200 other scientific publications on virology. In 2001 he received the
degree of DSc (honoris causa) from his alma mater, the University of Southampton.

Luciano Martini, born on May 14, 1927, in Milano-Italy is presently Emeritus

Professor at the University of Milano, where he was Professor of
Endocrinology and Chairman of the Department of Endocrinology from
1972 to 2003.
Author of more than 400 scientific publications in the fields of endocrinology,
neuroendocrinology, pharmacology, physiology of reproduction and steroid
He has received 4 Honorary Degrees: 3 in Medicine fromthe Faculties of
Medicine of the University of Liege-Belgium, of the University of Santiago de
Compostela-Spain and of the University of Pecs-Hungary and 1 in
Pharmacological Biotechnologies from the Faculty of Pharmacy of the
University of Milano-Italy.
Luciano Martini has been the President of the International Society of
Neuroendocrinology (19801984), of the International Society of
Endocrinology (19881992), of the European Federation of Endocrine Societies (19941998).
He has written and edited several volumes and textbooks.
Among those one may quote:
Neuroendocrinology, a textbook in 2 volumes, Academic Press, New York, 19661967.
Frontiers in Neuroendocrinology (volumes 19), Oxford University and Raven Press, New York, 19691985.
Clinical Neuroendocrinology, a textbook in 2 volumes, Academic Press, New York, 19771982.
Encyclopedia of Endocrine Diseases (4 volumes), Academic Press-Elsevier, San Diego, California, 2004.

Linda M. McManus, is a Distinguished Teaching Professor in the Departments

of Pathology and Periodontics and the Director of the Office of Postdoctoral
Affairs at the University of Texas Health Science Center, San Antonio, TX. She
conducts basic biomedical research focused on the cellular and molecular
regulation of inflammatory events in tissue injury and regeneration.
McManus is Past-President of the American Society for Investigative
Pathology, Director of a Cardiovascular Pathobiology Training Program, and
Co-Director of the Clinical and Translational Science Education Programs at
UT Health Science Center at San Antonio.
vi Editor Biographies

Charlene A. McQueen is recognized nationally and internationally as

researcher and educator. She was formerly a W.W. Walker Professor at
Auburn University Harrison School of Pharmacy, and a Professor in the
Department of Pharmacology and Toxicology at the University of Arizona.
She is currently Director, Integrated Systems Toxicology Division, National
Health and Environmental Effects Research Laboratory, US Environmental
Protection Agency. McQueen received her M.S. in Pharmacology from
New York University and Ph.D. in Human Genetics from the University of
Michigan. Her research is in the areas of pharmacogenomics, toxicogenomics
and chemical carcinogenesis. McQueen is an American Association for the
Advancement of Science Fellow (AAAS) and a Fellow in the Academy of
Toxicological Sciences (ATS). She received the Society of Toxicology (SOT)
Public Communications Award (2003) and the SOT AstraZeneca Traveling
Lectureship Award (2004). McQueen served on the National Research Council
Committee on Comparative Toxicity of Naturally Occurring Carcinogens, the
Environmental Health Sciences Committee of the National Institute of Environmental Health Sciences, the
Board of Scientific Councilors of the National Toxicology Program and the Board of Directors of ATS. She was a
Councilor of SOT and the International Society for the Study of Xenobiotics (ISSX) and President of the ATS
Board of Directors. She is currently a member of the Board of Trustees of the Health and Environmental
Sciences Institute. McQueen served on editorial boards of several journals including Drug Metabolism and
Disposition; she has edited several books and was the editor in chief for Comprehensive Toxicology.

Rick Mitchell is a graduate of the California Institute of Technology, The

Rockefeller University, and Harvard Medical School; he is the Lawrence
J. Henderson Professor of Pathology and Health Sciences and Technology at
Harvard Medical School. He is also the Associate Director of the combined
Harvard-MIT Division of Health Sciences and Technology (HST), an Associate
Master at Harvard Medical School, and Director of the HST Pathology course;
he has authored several chapters in Pathology textbooks. His clinical
responsibilities include autopsy and cardiovascular pathology as a Staff
Pathologist at Brigham and Womens Hospital in Boston, where he is also a
Vice President for Education in the Pathology Department. His research
focuses on the mechanisms of rejection in solid organ transplantation.
He and his wife Diane have two grown children, Matthew and Rebecca.

Stella Quah is Consultant and Adjunct Professor, Health Services and Systems
Research Program, Duke-NUS Graduate Medical School. She was awarded a
Fulbright-Hays scholarship from 1969 to 1971. The first part of her career as
researcher and educator took place at the Department of Sociology, National
University of Singapore (February 1973 to 30 June 2009). During that time she
was also granted sabbaticals as Research Associate and Visiting Scholar at the
Institute of Governmental Studies, University of California Berkeley
(198687); the Center for International Studies at the Massachusetts
Institute of Technology and the Department of Sociology at Harvard
University (199394); the Harvard-Yenching Institute, Harvard University
(1997); the Stanford Program in International Legal Studies, Stanford
University (1997); the National Centre for Development Studies, Australian
National University (2002); and the Walter H. Shorenstein Asia-Pacific
Research Center, Spogli Institute for International Studies, Stanford
University (2006). Stella Quahs professional activities include membership of Institutional Review Boards
and editorial advisory boards of various international refereed journals. She has published extensively on social
policy, family sociology and the sociology of health. Some examples of her publications on sociology of health
Editor Biographies vii

are: Encyclopedia of Health, Illness, Behavior & Society (Wiley Blackwell, 2014, Co-Editor with W.C. Cockerham
and R. Dingwall); International Encyclopedia of Public Health (Elsevier, 2008, Associate Editor-in-Chief, with
K. Heggenhougen); Crisis Preparedness: Asia and the Global Governance of Epidemics (Stanford Shorenstein APARC
and Brookings Institution, 2007); Caring for persons with schizophrenia at home: Examining the link between
family caregivers role distress and quality of life, (Sociology of Health and Illness, 36, 117, 2013, doi:
10.1111/1467-9566.12091); Gender and the burden of disease in ten Asian countries: An exploratory
analysis (Asia Europe Journal, 8, 4, 2011, 499502); Health ad Culture (in W.C. Cockerham, ed., The New
Blackwell Companion of Medical Sociology, Blackwell, 2010, 2746); Public image and governance of epidemics:
Comparing HIV/AIDS and SARS (Health Policy, 80, 2007, 253272).

George Richerson received a BS in Aerospace Engineering from Iowa State

University in 1980, and an MD and PhD in Physiology & Biophysics from
the University of Iowa in 1987. He did his Neurology Residency at Yale
University, and then joined the faculty at Yale in 1991. He rose to the rank
of Professor of Neurology at Yale University, and was Program Director of the
Neurology Residency at Yale-New Haven Hospital for 15 years, He returned to
Iowa City in 2010 to become Chairman of the Neurology Department.
Richerson has been Principal Investigator on numerous NIH grants focused
on two major areas of research. The first examines the role of serotonin
neurons in autonomic, thermoregulatory and central respiratory control,
particularly CO2 sensation. Using in vitro and transgenic approaches, his
laboratory has shown that serotonin neurons mediate changes in
wakefulness, breathing and autonomic function in response to blood CO2
levels. This research is related to the pathophysiology of sudden infant death
syndrome (SIDS), sudden unexpected death in epilepsy (SUDEP) and sleep
apnea. The second area of research examines the role of GABA transporters in epilepsy and the mechanism of
action of anticonvulsants. His lab has shown that GABA transporters regulate the level of tonic inhibition. They
also reverse easily, contributing to phasic inhibition, especially during seizures.
Richerson was elected to the American Neurological Association in 2003, was Chair of the NTRC Study
Section and has been on the editorial boards of the Journal of Neurophysiology and Respiratory Physiology &

Yi-Wei Tang is currently the Chief of the Clinical Microbiology Service at the
Memorial Sloan-Kettering Cancer Center and a Professor of Pathology and
Laboratory Medicine at the Weill Medical College of Cornell University in
New York City, USA. He obtained his medical training from Fudan University
Shanghai School of Medicine and Ph.D. in microbiology and immunology
from Vanderbilt University. He was a Lecturer and Clinical Fellow at the Mayo
Clinic and Assistant Professor, Associate Professor to Professor at the
Vanderbilt University School of Medicine. He has been engaged in medical
and molecular microbiology translational researches, aimed at developing and
evaluating new and advanced microbiological diagnostic testing procedures.
Tang ranks among the top of the scientific field in clinical and molecular
microbiology, as evidenced by his election as an Editor for the Journal of
Clinical Microbiology, an Associate Editor for the Journal of Molecular
Diagnostics, and a Fellow of the American Academy for Microbiology and of
the Infectious Disease Society of America. Tang has been recognized for his extraordinary expertise in the
molecular microbiology diagnosis and monitoring with over 200 peer-reviewed articles and book chapters in
this field during the past 20 years. Tang is the editor-in-chief of a coming Elsevier 3-volume book Molecular
Medical Microbiology, second edition.
viii Editor Biographies

Katherine L. Tucker is Professor of Nutritional Epidemiology in the

Department of Clinical Laboratory & Nutritional Sciences at the University
of Massachusetts Lowell. She also holds adjunct appointments at the
University of Massachusetts Medical School, the Friedman School of
Nutrition Science and Policy and the Jean Mayer USDA Human Nutrition
Research Center on Aging at Tufts University, and the Department of Health
Sciences at Northeastern University. Tucker has contributed to more than
250 articles in scientific journals. Her research focuses on dietary intake and
risk of chronic disease, including osteoporosis, cognitive decline, obesity,
metabolic syndrome, and heart disease, and on dietary methodology. She is
the director of an NIH funded Center for Population Health and Health
Disparities (CPHHD), which includes the Boston Puerto Rican Health Study,
a longitudinal study on the roles and interactions of stress, social support, diet,
health behavior and genetic predisposition in relation to health disparities in
Puerto Rican adults. She has collaborated for many years with the
Framingham Studies, particularly the Framingham Osteoporosis Study, and leads a Vanguard data analysis
center with the Jackson Heart Study. She is the Editor-in Chief of Advances in Nutrition, the review journal of
the American Society for Nutrition (ASN), and currently serves on the NIH study section for Kidney disease,
Nutrition, Obesity and Diabetes (KNOD) and as a member of the Food and Nutrition Board at the Institute of
Medicine. She is also an associate editor for Public Health Nutrition, and was a co-editor of the recently published
11th edition of the textbook, Modern Nutrition in Health and Disease. She is a past-chair of the Nutritional
Sciences Council at the American Society for Nutrition (ASN) and past-Associate Editor for the Journal of
Editors Note
MJ Caplan, Yale University School of Medicine, New Haven, CT, USA
2014 Elsevier Inc. All rights reserved.

Introduction to the Encyclopedia of Biomedical Sciences 1

Physiology 2
Pathology 2
Cell Biology 2
Genetics 3
Biochemistry and Molecular Biology 3
Developmental Biology 3
Cancer Biology 3
Microbiology, Infectious Disease and Immunobiology 3
Neurobiology 4
Pharmacology 4
Biotechnology 4
Nutrition 4
Toxicology 5
Epidemiology and Public Health 5

Introduction to the Encyclopedia of Biomedical Sciences

Fueled by the unbridled energy of the Enlightenment, in 1750 the French scholar Denis Diderot undertook the task of producing an
Encyclopedia whose goal was no less ambitious than the compilation of the full corpus of human knowledge in the arts and
sciences. As I contemplate what might seem to be the comparatively miniscule undertaking of assembling an Encyclopedia of that
very limited subset of human endeavor that is encapsulated within disciplines of the Biomedical Sciences, I cannot help but think
that Diderot had it easy. After all, while I am in no position to diminish the extraordinary deluge of insight and creativity that
swelled during the Enlightenment, it seems to me that by todays standards the font of knowledge available to even the
Enlightenments deepest thinkers was rather shallow. Modern science was in its infancy, and the shelves in its storehouse of
verified facts were just beginning to be stocked.
Whereas Diderot and his contemporaries inhabited a world that had yet to see smart phones or widespread indoor plumbing,
we live in an age of information whose density might best be described as fractal. The closer one looks into any defined body of
current knowledge, the more one is (or should be) daunted by its undiminished enormity. In todays compendium, every subtopic
in any organizational hierarchy seems to possess a dimensionality, richness and complexity that is comparable to that of the parent
topic from which it was spawned. This presents any modern day would-be encyclopedist with an enormous challenge, and it is
probably not too self-serving to posit that the Biomedical Sciences exemplify this challenge as well as does any contemporary
intellectual endeavor.
Within the last half century, the information density of the Biomedical Sciences has quite literally undergone the sort of
exponential growth that bacteria experience when cultivated in a nutrient rich environment. Furthermore, the density of this
information extends across biological disciplines and across scales of biological resolution. Whether one endeavors to understand a
single proteins functional properties by defining its structure at atomic resolution or focusses instead on the physiological
implications of that proteins function in the setting of a cell, tissue, organ or organism, one must of necessity assimilate a body
of knowledge whose magnitude might well have caused even the indomitable Diderot to question the wisdom of trying to unite
that knowledge within a single resource. Furthermore, that body of knowledge is not static. It transforms with remarkable rapidity
and in thoroughly unpredictable directions.
How then, can we be so presumptuous as to propose that the present project of assembling a useful Encyclopedia of Biomedical
Sciences is not doomed by its own enormity? The editors of the present work have been continually conscious of this question, and
been inspired by it to think about designs that ensure that this Encyclopedias value will transcend the challenges that are imposed
by its scope. The structure that we have developed is built, first and foremost, upon an enormous foundational body of knowledge
that has been assembled and curated by leading experts representing Biomedical Sciences many and diverse disciplines. At its
inception, this Encyclopedia of Biomedical Sciences is constituted of many thousands of individual entries. Furthermore, and
perhaps more importantly, the experts that have assembled this works foundation will continue to refine, expand, revisit and revise
their contributions. The work will grow and evolve along with the fields of knowledge that it explores.
As a child I believed that the massive, multivolume set of encyclopedias that proudly occupied a substantial fraction of our
bookshelves was complete and authoritative, and that it was an infallible and timeless source of everything that was knowable.
I was blissfully unaware of the fact that, with each passing moment, that encyclopedia was one moment closer to becoming

Reference Module in Biomedical Research 1

2 Editors Note

a charming antique. To be useful, the currency of any resource devoted to the Biomedical Sciences must be monitored and
maintained to ensure that incorporates all of the latest information and sheds those concepts that have become outmoded. It is not
enough, however, to simply permit any such resource to be continually and uncritically fed from the gushing spring of new
information. Unfiltered information may be contaminated with noise that that drowns out essential messages and central themes.
All of the foundational content that has been included in the present Encyclopedia of Biomedical Sciences has been subjected to
rigorous editorial review for validity, currency and importance. Furthermore, the Editors and authors of this work will remain
engaged in the process of ensuring that it remains up to date through the addition of new information whose relevance and validity
have been vetted by recognized experts. Thus, the work promises to maintain an organic and vital connection to the fields that it
Finally, the boundaries that define the subdisciplines that together constitute the Biomedical Sciences grow ever less distinct.
Thus, any reference work that compartmentalizes its content into categories defined by historical convention rather than current
understanding risks rendering itself unwieldy. Furthermore, such a classical design fails to reveal the threads that interconnect
nodes of information within a discipline and across disciplinary borders. One of the principal complications in designing the
present work has been to create an architecture that celebrates rather than conceals this web. Ideally, this architecture should allow
its users both to exercise their ingenuity and to enjoy the pleasure of serendipitous discovery as they crawl along these threads. The
philosopher of science Jacob Bronowski suggested that creativity in any discipline might be described as the act of revealing a
connection that had not been previously recognized. We hope to produce a reference work that serves as a catalyst for creativity
according to this definition. Furthermore, at the risk of revealing myself to be a curmudgeonly anachronism, I must confess that
I feel that the extraordinarily sophisticated search tools that power the internet, and thus our access to most of the information that
we can readily exploit, deny us the joy of accidentally finding things that we were not looking for. Some of the most interesting
things that I have found in libraries resided in the volume that sat next to the one that I was originally seeking. We hope to continue
to refine the interface for this Encyclopedia of Biomedical Sciences so that it reveals the intrinsic connectedness of its content and
thus allows a user to appreciate unanticipated connections that might never have been uncovered in a simple directed search. This
architecture is a work in progress, and its ongoing creation constitutes one of the most exciting aspects of this major project.
While the boundaries that separate the core disciplines within the biomedical sciences progressively blur, these core disciplines
nonetheless constitute useful intellectual frameworks around which to organize the editorial task of assembling and curating the
content of the Encyclopedia of Biomedical Sciences. Our Editorial Board is composed of experts drawn from each of these
disciplines, and they bring to this project their insights into the major tenets and questions that motivate these fields. It is
worthwhile, therefore, to introduce several of these disciplines and to provide very brief overviews of their primary foci.


Depending upon how it is defined, physiology is perhaps the oldest and most interconnected of the disciplines within the
Biomedical Sciences (in the interest of full disclosure I should point out that I am a Physiologist and thus may be betraying just
a wee bit of chauvinism). In the broadest sense, physiology is the study of how the body maintains a constant and hospitable
internal milieu. This concept was first formulated in the nineteenth century by French physiologist Claude Bernard. American
physiologist Walter Canon subsequently coined the term homeostasis to summarize the multitude of processes that are required
to ensure that an organism is able to maintain a composition that differs dramatically from that of its surrounding and often hostile
environment. These processes occur at the level of cells, tissues, organs and organisms. They involve the generation and expenditure
of metabolic energy, and they are controlled by networks of signals and elegant feedback loops. Many of these signals and feedback
loops are the province of the Endocrine System, which serves as a master control system that monitors, modulates and integrates
physiological function. Physiology explores the molecules, messages and mechanisms through which homeostasis is maintained
and that determine its parameters.


Any machine as exquisitely complex as a human body must, of necessity, be subject to all manner of malfunctions. Much of what
we have learned about normal human physiology derives from efforts to understand the causes and effects of these malfunctions.
Human disease arises when extrinsic or intrinsic forces alter or interrupt the local or systemic mechanisms that maintain
homeostasis. Pathology is a discipline that endeavors to understand how and why normal function is perturbed, and what
consequences result from such perturbations.

Cell Biology

The cell is the fundamental building block of the human organism. Furthermore, each tissue and organ is constituted of collections
of highly specialized cell types whose physical and biochemical properties are exquisitely well adapted to their particular jobs.
Consequently, any sophisticated understanding of Biomedical Science must be predicated upon an appreciation of the structures
Editors Note 3

that constitute cells and the means through which these structures are deployed both to maintain the cells viability and to ensure its
utility to the larger organism. Cell biology explores this relationship between cellular form and function.


Every nucleated human cell carries within it a nearly complete set of the instructions required to assemble a complete human being.
Furthermore, these instructions, which are embodied in the genome, are constantly referenced in order maintain cellular structure
and to permit cellular responses to physiological stimuli. A large subset of human diseases arise from inherited or spontaneous
alterations in the genome or in the machinery that tends it. Genetics seeks to understand how these instructions are encoded,
reproduced, interpreted and enacted. Recent technical advances and concerted efforts have produced an extraordinarily detailed
insight into the nature and dynamics of the human genome. Genetics endeavors to understand the mechanisms that govern the
structure and stability of the genetic material, and that control the expression of the genes that it encodes.

Biochemistry and Molecular Biology

Every biological process is, in essence, an orchestrated collection of chemical reactions. Biological structures, from the level of single
molecules to the level of complex systems, have evolved to ensure that these reactions take place efficiently, in the right place and at
the right time. The metabolism of nutrients, the generation of energy from that metabolism, and the exploitation of that energy to
build, maintain and regenerate all of the structures of the cell all exemplify the chemical nature of biological processes.
Biochemistry endeavors to understand the structures of biological molecules, to understand how those structures define their
chemical properties, and to establish how those chemical properties are employed and controlled. In many ways, molecular
biology can be seen as the engine that has driven the remarkable progress in the Biomedical Sciences that has occurred over the last
four decades. The insight it has provided into the nature and expression of the information contained in the genome has been
fundamental in efforts to understand the mechanisms and machinery of life. The tools it has provided have permitted the
mechanisms and machinery of life to be explored, manipulated and repaired with remarkable precision.

Developmental Biology

The union between sperm and egg sets in motion a program through which a single cell gives rise to a fully formed organism. This
developmental program employs highly orchestrated cell division, differentiation, death, movement and communication to
assemble a human being according to the instructions that are encoded in its genome. Considering its complexity, and its intrinsic
requirement for tremendous spatial and temporal precision, development is a remarkably robust process. Despite this robustness,
however, development is susceptible to intrinsic and environmental perturbations that underlie a wide range of human diseases.
Developmental biology investigates the processes which through all of the structures that constitute a human are generated and the
causes and consequences of errors in these processes.

Cancer Biology

Normally, cell growth and replication are tightly controlled, so that these processes occur only when and where they are needed.
Cancer is caused by a breakdown in this control, resulting in dysregulation of cellular proliferation and loss of differentiated
cellular identity to create neoplastic growth. Furthermore cancerous transformation can create cells that lose their attachment to
their normal tissue architecture and can travel through the body to metastasize, which is to say they invade and take up residence in
other tissues. Neoplasms develop through a wide variety of mechanisms, take many forms and can exert an enormous number of
profound effects on their local environments and on the physiological functioning of their host organism. Cancer biology
endeavors to understand the mechanisms through which cancer develops, the varieties of its forms, and its vulnerabilities that
render it susceptible to therapy.

Microbiology, Infectious Disease and Immunobiology

We tend to think of microorganisms as enemies. Certainly, we are subject to constant assault by a rogues gallery of microorganisms
that wish to do us harm. Bacteria, viruses, protozoans and parasites endeavor to exploit our nutrient rich internal environment and
to subvert our metabolism to their own nefarious ends. It is becoming ever clearer, however, that this view of microorganisms is
overly simplistic and negative. We co-exist with massive populations of commensal organisms that colonize our every nook and
cranny and that appear to participate in defining who we are and how we interact with our environment. Microbiology is a
discipline that focusses on understanding the nature of those microorganisms that cause disease and those that help to keep us
4 Editors Note

healthy. Our bodies employ numerous defenses in our efforts to prevent microorganisms from producing infectious diseases. The
persistent threat of infectious diseases, even in our present era of hygiene and antibiotics, provides ample evidence that microor-
ganisms have developed and continue to develop remarkably clever tools with which to subvert our best defenses. The immune
system constitutes our most sophisticated defense against infection. The immune system employs sophisticated surveillance
methods to recognize elements in our bodies that do not belong to us, and deploys manifold defenses to isolate or destroy
those elements. Not surprisingly, deficits in immune function can render us susceptible to the malevolent intentions of infectious
microorganisms. Conversely, however, an overly exuberant immune system can produce disease by attacking and destroying our
own healthy tissue. Immunobiology investigates the mechanisms through which the many cell types that contribute to the immune
system collaborate with one another to mount and regulate a response to foreign invaders.


Since the time of Rene Descartes in the mid seventeenth century scholars have debated how the physical entity of the brain is able to
endow us with our conscious and unconscious minds. The nervous systems endows us with our capacity to interact in sophisticated
ways with our environments, with each other and with ourselves. Our every thought, action, emotion and sensation derives from
signals that ricochet among the almost unfathomably complex network of interconnected neurons in our brains. Furthermore, the
nervous system monitors and regulates almost every aspect of our physiological functioning. Not surprisingly, therefore, neuro-
biology is a vast topic. It ranges in scope from the cell biology and biochemistry of individual neurons to the behaviors that emerge
from massive neuronal ensembles. It employs tools in its investigations that range from the analysis of single molecules to studies
that explore the neuronal activity that underlies human thought and behavior. As might be expected of such a complex entity, the
nervous system is subject to myriad varieties of pathologies that are important both for their impact on the lives of those that
endure them and for what they teach us about how the nervous system functions.


Most peoples primary interaction with the fruits of the Biomedical Sciences occurs when they visit a pharmacy to fill a physicians
prescription for a drug to treat some ailment. Some of those drugs derive from natural substances, while some are entirely synthetic.
The medical utility of some of those drug substances were recognized several centuries ago, while some are the products of the
most recent efforts to fight disease. Pharmacology is the science that focuses on discovering new drug substances, understanding
how they work and defining their interactions with the body. In its modern incarnation, pharmacology seeks to identify drug
targetsthat is, activities or processes that are relevant to a disease state and that are accessible to selective biochemical
manipulation. This requirement for selectivity is extremely important, since the goal in developing a new drug substance is to
find an agent that affects only its designated target without off target actions and with a minimum of side effects. Thus,
pharmacology integrates an enormous body of knowledge about normal physiology and pathobiology in order to develop
novel approaches to treat disease that are both safe and effective.


When most people think of the products of engineering, they probably visualize highways, bridges and dams or microchips and
high definition video screens. There is another field of engineering, however, whose efforts are devoted to applying technology to
provide new tools with which to treat disease and ease discomfort. As its name implies, biotechnology seeks to engineer solutions
to biomedical problems. Some of these solutions are often seen and widely known, such as artificial limbs and hearing aids,
whereas others are much less visible, such as nano-encapsulated drug delivery systems and implantable electrodes that treat
neurological diseases. In each of these cases, the goal is to find novel ways to interface the tools of technology with human biology
in order to address a substantial biomedical problem.


Our metabolism requires fuel, and that fuel is provided by our diet. The science of nutrition explores the nature of our metabolic
needs and the means through which dietary substances satisfy them. While for millennia the human diet was viewed as a beneficent
source of sustenance, the past few decades have revealed that the diet can also be significant source of pathology. Excessive or
unbalanced nutrient consumption is the primary cause of obesity and its associated pathologies, whose prevalence throughout the
world has reached epidemic proportions. Understanding the factors that lead to obesity and developing strategies to reverse them is
one of the great challenges of modern nutrition science and one that will impact the Biomedical Sciences for decades to come.
Editors Note 5


We live in a world that is rife with poisons. Nature has developed all manner of toxic substances that have the capacity to do us
harm. Our own scientific progress has added substantially to this arsenal of compounds that have the capacity to interfere with vital
aspects of our fragile biochemistry. Toxicology endeavors to understand these compounds, how we come into contact with them,
how they perturb our normal function and how we can prevent or treat exposure to them. Understanding the mechanisms through
which individual toxins damage us also provides new insights into our normal physiology.

Epidemiology and Public Health

Disease effects individuals and populations. While other components of the Biomedical Sciences teach us about the mechanisms
through which disease perverts an organisms normal function, Epidemiology and Public Health teaches us how disease develops
in, spreads through and impacts a community. Clearly in the context of infectious conditions it is critically important to understand
how a communitys living conditions and practices facilitate or impair the spread of disease. This statement is just as true, however,
in the context of all manner of human pathologies ranging from malnutrition to obesity and from birth defects to cancer. Our
societies are the sources of both major weapons in the war on disease and major causes of its propagation. Understanding the
interface between the Biomedical Sciences and human communities is at the forefront in the efforts of Biomedical Scientists to
improve the health of the world.

Editor in Chief
Michael J. Caplan Luciano Martini
Yale University School of Medicine, USA University of Milan, Italy
Subject: Endocrinology
Subject Editors
Linda M. McManus
Walter F. Boron
University of Texas Health Science Center, USA
Case Western Reserve University School of Medicine, USA
Subject: Pathobiology of Human Disease
Subject: Medical Physiology
Charlene A. McQueen
Emile L. Boulpaep
US Environmental Protection Agency, USA
Yale University School of Medicine, USA
Subject: Toxicology
Subject: Medical Physiology
Rick Mitchell
Ralph A. Bradshaw
Harvard Medical School, USA
University of California San Francisco, USA
Subject: Pathobiology of Human Disease
Subject: Cell Biology
Stella R. Quah
David B. Bylund
Duke-NUS Graduate Medical School, Singapore
University of Nebraska Medical Center, USA
Subject: Epidemiology and Public Health
Subject: Pharmacology
George B. Richerson
Bruce M. Carlson
University of Iowa, USA
University of Michigan, USA
Subject: Neurobiology
Subject: Developmental Biology and Human Embyology
Philip D. Stahl
S.J. Enna
Washington University School of Medicine, USA
University of Kansas Medical School, USA
Subject: Cell Biology
Subject: Pharmacology
Yi-Wei Tang
Ilpo Huhtaniemi
Memorial Sloan-Kettering Cancer Center, USA
Imperial College London, UK
Subject: Microbiology
Subject: Endocrinology
David T. Teachey
Shashikant Shashi Kulkarni
University of Pennsylvania, USA
Washington University School of Medicine, USA
Subject: Cancer
Subject: Cancer; Genetics and Genomics
Katherine L. Tucker
Brian W.J. Mahy
University of Massachusetts Lowell, USA
formerly of Cambridge University, UK, and Centers for
Subject: Human Nutrition
Disease Control and Prevention, USA
Subject: Virology

Reference Module in Biomedical Research 1


This work is a composite entity.

It originates in a nest of many thousands of articles which were originally published in Elseviers Major
Reference Works portfolio.
These foundational reference works are authoritative, field-spanning, and in many cases famous. But they
are as bound to their year as they are to their edition. And therefore they are static works, and less useful as they
age and as science changes.
Within this Reference Module, the editorial board has selected, curated, and brought up to date the most
relevant and related articles from these classic foundations, rehanging them against a new organic taxonomy to
represent the full domain of biomedicine the subject hierarchy. This hierarchy, like the module, is a living
Articles within this module are not static, but kept in a dynamic state of field-specific currency. From
launch, and in perpetuity thereafter, a process of time-stamped currency review is applied to the whole module
content. At launch, and throughout development as and when mandated by currency review, an updating
process is applied. As science changes, so does this Reference Module.
With the ambition being to represent the full domain of Biomedical Sciences, a notably fast-moving, many-
faceted and interconnected domain, this cannot but be an ongoing activity, and involve the contribution of
many thousands of individuals from many branches of the field.
The module could not have been created without the work of countless contributors and editors who
together built the families of constituent reference works at Elsevier and Academic Press and over many years.
Here the publisher would like to convey its particular thanks and acknowledgements to the generations of
researchers and clinicians who contributed their expertise, time, and boundless energy to the making of
Elseviers biomedical sciences reference portfolio.
Of particular note in the formation of the Reference Module in Biomedical Sciences are the following
John Abelson, UC San Francisco, USA
Michael Aschner, Vanderbilt University Medical Center, USA
Peter J. Barnes, Imperial College London, UK
Hollie Black, Case Western Reserve University School of Medicine, USA
Daniel Blanchard, UCSD Sulpizio Cardiovascular Center, USA
Alisha Bouzaher, Case Western Reserve University School of Medicine, USA
Bruce A. Bunnell, Tulane University School of Medicine
Stephanie Bury-Mone, Laboratory of Biology and applied pharmacology (LBPA), France
Lisa Campo-Engelstein, Albany Medical College, USA
Jose Carlos Rodrguez-Cabello, Universidad de Valladolid, Spain
Francesco Cellesi, Politecnico di Milano, Italy
Lucio Costa, University of Washington, USA
Larry Couture, Memorial Sloan-Kettering Cancer Center, USA
Abina M. Crean, University College Cork, Ireland
Marie Csete, UC San Diego, USA
Maxime Culot, Universite dArtois, France
Tim E. Darsaut, University of Alberta Hospital, Canada
Walter Doerfler, University of Cologne, Germany
Lorenzo Fassina, University of Pavia, Italy

Reference Module in Biomedical Research 1

2 Special Acknowledgements

Guy M. Genin, Washington University in St. Louis, USA

Raja Ghosh, McMaster University, USA
Griet L. Glorieux, University Hospital of Ghent, Belgium
Marie Jose T.H. Goumans, Goumans, the Netherlands
Heidi Hamm, Vanderbilt University Medical Center, USA
Peiman Hematti, University of Wisconsin School of Medicine and Public Health, USA
Wilhelm Hofstetter, University of Bern, Switzerland
Donna Holmes, Washington State University, USA
Jean Kanellopoulos, Universite Paris, France
Kevin C. Kemp, University of Bristol, UK
Wasim Khan, University College London, UK
Martin Kohlmeier, The University of North Carolina, USA
Petri P. Lehenkari, Oulun Yliopisto, Finland
Reto Luginbuhl, University of Bern, Switzerland
Conor OMahony, Tyndall National Institute at National University of Ireland, Ireland
Stayci Martin, Case Western Reserve University School of Medicine, USA
Shlomo Melmed, California Institute for Regenerative Medicine, USA
Ziad Memish, Ministry of Health, Saudi Arabia
Sandro Michelini, European Society of Lymphology, Italy
Michel M. Modo, Kings College London, UK
Samuel Monebi, Case Western Reserve University School of Medicine, USA
Michael Muehlenbein, Indiana University, USA
Amalia Namath, Case Western Reserve University School of Medicine, USA
Hayato Ohshima, Niigata University Graduate Sch. of Medical & Dental Sciences, Japan
Laurent Pierot, Universite de Reims Champagne-Ardenne, France
Mariah Poage, Case Western Reserve University School of Medicine, USA
Sanela Radu, Case Western Reserve University School of Medicine, USA
Giuseppe Remuzzi, University of Washington, USA
Kelly Sambrook, Case Western Reserve University School of Medicine, USA
Andromachi Scaradavou, Memorial Sloan-Kettering Cancer Center, USA
Beth Shaz, Emory University School of Medicine, USA
Melvin I. Simon, UC San Diego, USA
Deborah Spector, University of California, USA
Paul Trainor, Stowers Institute for Medical Research, USA
Mitchell Watsky, University of Tennessee Health Science Center, USA
Leslie Weiner, University of Southern California, USA
Adam Wheeler, Case Western Reserve University School of Medicine, USA
Phillip Yang, Stanford University, USA
Emery Young, Case Western Reserve University School of Medicine, USA