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CCMB Distinguished Lectures 2006-2007
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J. Craig Venter is one of leading scientists of the 21st century for his visionary
contributions in genomic research. He is founder and president of the J. Craig Venter
Institute and the J. Craig Venter Science Foundation. The Venter Institute conducts
basic research that advances the science of genomics; specializes in high volume
genome sequencing, and explores the ethical and policy implications of genomic discoveries
and advances. The J. Craig Venter Science Foundation supports both the Venter Institute
and The Institute for Genomic Research (TIGR), an affiliated research organization
led by Claire M. Fraser, Ph.D. Venter founded TIGR in 1992.
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Craig Venter J. Craig Venter Institute
Genomics: from Medicine to the Environment
Abstract: TBA
December 6th
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A graduate of Columbia University, Professor Cooper also received the M.A. and Ph.D.
degrees from that University. He spent a year at the Institute for Advanced Study
and taught at the University of Illinois and Ohio State University before coming
to Brown in 1958. A fellow of the American Physical Society, American Academy of
Arts and Sciences, Member of the Natural Academy of Sciences, American Philosophical
Society, Associate, Neurosciences Research Program, he was an Alfred P. Sloan Research
Fellow from 1959 to 1966 and a Guggenheim Fellow in 1965-66. He has carried out
research at various institutions including the Princeton Institute for Advanced
Study, the European Organization for Nuclear Research (CERN) in Geneva, Switzerland.
Professor Cooper is a Nobel Laureate, having been awarded the Nobel Prize in 1972
jointly with Bardeen and Schrieffer for their work on superconductivity. He is the
Thomas J. Watson, Sr. Professor of Science at Brown, and Director of the Institute
for Brain and Neural Systems.
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Leon Cooper Thomas J. Watson, Sr. Professor of Physics, Brown University
Is Theory Possible in Neurosciences?
Abstract: TBA
December 6th
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Dr. David L Barker is Vice President and Chief Scientific Officer at Illumina, Inc.,
in San Diego, California. Dr. Barker served from 1998 to 2000 as Vice President
and Chief Science Advisor at Amersham Biosciences, now part of General Electric.
From 1988 to 1998, Dr. Barker held senior positions, including Vice President of
Research and Business Development, at Molecular Dynamics, Inc., until the acquisition
of Molecular Dynamics by Amersham. He serves on the Boards of Directors of Excellin
Life Sciences Inc., Cell Biosciences, and Microchip Biotechnologies, Inc. In his
academic career, Dr. Barker conducted interdisciplinary research in neurobiology
as a postdoctoral fellow at Harvard Medical School, Assistant Professor at the University
of Oregon and Associate Professor at Oregon State University. Dr. Barker holds a
BS with honors in Chemistry from the California Institute of Technology and a PhD
in Biochemistry from Brandeis University.
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David Barker
Vice President and Chief Scientific Officer Illumina, Inc.
Capturing Common Variation in the Human Genome on a Single Microarray
Abstract:
The International HapMap Project provided a framework for accessing all common variation
in the human genome through SNP genotyping. The development of the Infinium® Assay
has enabled true whole genome genotyping: One can now genotype more than 650,000
SNPs on a single microarray, enough to capture essentially all common human variation,
at a cost per SNP three orders of magnitude less than six years ago. This methodology
is being used by researchers around the world to genotype tens of thousands of patient
samples in efforts to discover the genetic basis of common diseases such as cancers,
heart disease, arthritis, and diabetes. Detailed scrutiny of many human genomes
has revealed that both large and small deletions of genomic sequence are surprisingly
frequent in "normal" genomes, and are commonplace in cancer cells. These variations
can also be analyzed by SNP genotyping using appropriate software tools. The avalanche
of data generated by whole genome genotyping presents challenges for computational
biology, as valid associations to disease-causing genes are hidden among literally
billions of data points generated by each study. In addition, further understanding
will require the integration of genomic, epigenetic, and gene expression data by
computational tools that reveal underlying mechanisms.
December 6th
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M.D., D.T.M.H., CAPT, MC, USN (RET) has over 20 years of experience building and
managing large, successful research and development programs. From 1987-2001 he
was Director of the Malaria Program at the Naval Medical Research Center where he
built a focused professional team of over 100 individuals in the United States and
overseas working on all aspects of malaria research, but especially vaccine development
and genomics. Dr. Hoffman and his team were leaders in the effort to sequence the
P. falciparum genome and conducted the first studies in the world that showed that
DNA vaccines elicited killer T cell responses in humans. In early 2001 Dr. Hoffman
retired from the Navy and joined Celera Genomics as Senior Vice President of Biologics
to create a program to utilize genomics and proteomics to produce new biopharmaceuticals.
He established this program, organized the effort that successfully sequenced the
genome of the mosquito responsible for most transmission of malaria in Africa, Anopheles
gambiae, and left Celera in August 2002 to found Sanaria. He holds several professorships,
and chairs or serves on multiple advisory boards. He is a past president of the
American Society of Tropical Medicine and Hygiene, has edited two books on malaria
vaccine development, been the author of more than 325 scientific publications, and
has numerous patents. He received his B.A. from the University of Pennsylvania,
M.D. from Cornell University Medical College, Diploma in Tropical Medicine and Hygiene
from the London School of Hygiene and Tropical Medicine, and did residency training
at the University of California, San Diego. He is board certified in Family Practice.
In 2004 he was elected to membership in the Institute of Medicine of the National
Academies.
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Stephen Hoffman
Chief Executive and Scientific Officer, Sanaria
The Journey from Genomics, Molecular Immunology and DNA Vaccines to an Attenuated Whole Parasite Malaria Vaccine
Abstract:
Scientists have been working for more than 25 years to develop malaria vaccines.
Modern, recombinant, subunit malaria vaccine development depends in large part on
characterizing mechanisms of protective immunity and the antigen targets of these
protective immune responses, and developing vaccine delivery systems that induce
the required immune responses against the identified targets. The genomic sequences
of Plasmodium falciparum and other malaria causing parasites and Homo sapiens have
provided a wealth of information upon which to build experiments designed to characterize
immune mechanisms and antigen targets, and optimize vaccine delivery systems. Translating
this information into highly effective, sustainable malaria vaccines has been a
difficult, expensive, long process. In fact only one P. falciparum protein which
was discovered and shown to be protective using modern scientific methods, the circumsporozoite
protein (PfCSP), has been shown to reproducibly elicit immune responses that prevent
infection in humans. The magnitude and longevity of this protection is not comparable
to the protection elicited by vaccines in general use for protecting against other
infectious agents Because of the importance of malaria vaccine development, in parallel
there are over 70 other approaches to subunit, modern, recombinant malaria vaccine
development in progress. At Sanaria we are working on a completely different approach
to malaria vaccine development. The goal is to develop a practically manufactured
and administered, safe, non-toxic, effective, non-replicating, metabolically active
whole parasite P. falciparum sporozoite vaccine. This approach is based on the fact
that when the immunogens, radiation attenuated P. falciparum sporozoites, are administered
via the bites of infected mosquitoes, they elicit immune responses that completely
protect greater than 90% of human recipients against experimental P. falciparum
challenge for at least 10 months. During the last 3 years we have demonstrated that
it is feasible to immunize by a clinically practical route, produce adequate quantities
of P. falciparum sporozoites, and produce a vaccine and release assays that meet
regulatory standards and cost of goods requirements. Data describing this progress,
and plans for cGMP manufacture, clinical testing, development, and licensing of
an attenuated sporozoite vaccine designed to significantly reduce the 2700 to 8100
daily deaths in infants and children caused by malaria will be discussed.
December 6th
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Jeffrey Skolnick is the Director of the Center for the Study of Systems Biology
in the School of Biology at the Georgia Institute of Technology and the Georgia
Research Alliance Eminent Scholar in Computational Systems Biology. He attended
graduate school in Chemistry at Yale University, receiving a Ph.D. in Chemistry
in polymer statistical mechanics. He then held a postdoctoral fellowship at Bell
Laboratories. Next, he joined the faculty of the Chemistry Department at Louisiana
State University, Baton Rouge. Then, he moved to Washington University, where he
was subsequently appointed Professor of Chemistry. There he was also Director of
the Institute of Macromolecular Chemistry at Washington University. He joined the
Department of Molecular Biology of the Scripps Research Institute, where he held
the rank of Professor. Among his awards is an Alfred P. Sloan Research Fellowship
and he is a Fellow of the American Association for the Advancement of Science, a
Fellow of the Biophysical Society, a Fellow of the St. Louis Academy of Science
Recently, he moved to the Georgia Institute of Technology. He is the author of over
270 publications and has served on numerous editorial boards including Biophysical
Journal, Biopolymers, Proteins, and the Journal of Chemical Physics. He is also
a cofounder of an early stage structural proteomics company, GeneFormatics, and
his software has been commercialized by Tripos. His current research interests are
in the area of computational biology and bioinformatics. He has developed algorithms
for the prediction of protein structure and folding pathways from protein sequence.
In addition, he has been extensively involved in the simulation of membranes and
membrane peptides. Most recently, he has developed approaches to predict protein
function from amino acid sequence, to assign proteins to pathways, to predict protein-protein
interactions, and to predict druggability that can be applied to entire genomes
as well as in the development of tools for metabolic profiling and cancer diagnostics.
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Jeffrey Skolnick Professor, Director, Center for the Study of Systems Biology,
Georgia Tech
Prediction of Protein Structure, Function
and Druggability on a Proteomic Scale
Abstract: TBA
December 7th
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Dr. King is Professor of Molecular Biology at MIT, and an authority on the genes
and proteins of micro-organisms. Prof. King was a founder of the Council for Responsible
Genetics and Co-Chair of its Committee on the Military Use of Biological Research.
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Jonathan King Professor of Molecular Biology, MIT
Why deciphering the Amino Acid Sequence Rules for Protein Folding is so difficult:
The Case of the Beta-sheet Fold
Abstract: TBA
December 7th
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Dr. Pevzner is Ronald R. Taylor Chair professor of Computer Science and ZDirector
of the Center for Algorithmic and Systems Biology at University of California, San
Diego. He holds Ph.D. (1988) from Moscow Institute of Physics and Technology, Russia.
Dr. Pevzner has authored graduate textbook "Computational Molecular Biology: An
Algorithmic Approach" in 2000 and undergraduate textbook "Introduction to Bioinformatics
Algorithms" in 2004 (jointly with Neal Jones). He was named Howard Hughes Medical
Institute Professor in 2006.
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Pavel A. Pevzner
Ronald R. Taylor Professor of Computer Science, UCSD
The Third Rebuttal of the Random Breakage Theory
Abstract:
Rearrangements are genomic "earthquakes" that change the chromosomal architectures.
The fundamental question in molecular evolution is whether there exist "chromosomal
faults" where rearrangements are happening over and over again. In 1984 Nadeau
and Taylor proposed Random Breakage Model (RBM) of chromosome evolution that recently
caused a controversy. RBM postulates that rearrangements are "random", and thus
there is no rearrangement hot-spots in mammalian genomes. It was embraced by biologists
from the very beginning (due to its prophetic prediction power) but in 2003 was
refuted by Pevzner and Tesler who gave a non-constructive argument against RBM using
a combinatorial theorem. They further proposed Fragile Breakage Model that postulates
that mammalian genomes represent a mosaic of fragile and solid regions. However,
the rebuttal of RBM caused a controversy and shortly after Pevzner-Tesler work was
published, Sankoff and Trinh, 2004 gave a rebuttal of the rebuttal of RBM. Sankoff
and Trinh, 2004 did not question the validity of combinatorial arguments in Pevzner
and Tesler, 2003 but instead argued that the synteny block generation algorithm
is parameter-dependent and that rebuttal of RBM is more subtle than it may look
like at the first glance. Recently, Peng et al., 2006 re-examined the Sankoff-Trinh
arguments and demonstrated that they fell victims to their inaccurate synteny block
generation algorithm that fails even on small toy examples. They further demonstrated
that if Sankoff and Trinh had fixed these problems and chosen realistic parameters,
their arguments against Pevzner and Tesler, 2003 would disappear. Sankoff, 2006
recently acknowledged the flaw in Sankoff and Trinh, 2004 but still appeared reluctant
to acknowledge the validity of the Pevzner-Tesler rebuttal of RBM, this time arguing
that a larger set of rearrangement operations (e.g., transpositions) may explain
the "fragile regions" and that the "block deletion" argument in Sankoff and Trinh,
2004 is still valid. In this talk we give a rebuttal of the rebuttal (Sankoff, 2006)
} of the rebuttal (Peng et al., 2006) of the rebuttal (sankoff and Trinh, 2004)
of the rebuttal (Pevzner and Tesler, 2003) of RBM.
December 7th
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Dr. Shaw is the chief scientist of D. E. Shaw Research and a senior research fellow
at the Center for Computational Biology and Bioinformatics at Columbia University.
He and his research group are currently involved in the design of massively parallel
machine architectures and algorithms for high-speed molecular dynamics simulations,
and in the use of such simulations to study biomolecular systems of interest from
both a scientific and a pharmaceutical perspective.
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David E. Shaw
Chief Scientist, D. E. Shaw Research; Center for Computational Biology and Bioinformatics, Columbia University
New Architectures for a New Biology
Abstract:
Some of the most important outstanding questions in the fields of biology, chemistry,
and medicine remain unsolved as a result of our limited understanding of the structure,
behavior and interaction of biologically significant molecules. The laws of physics
that determine the form and function of these biomolecules are well understood.
Current technology, however, does not allow us to simulate the effect of these laws
with sufficient accuracy, and for a sufficient period of time, to answer many of
the questions that biologists, biochemists, and biomedical researchers are most
anxious to answer. This talk will describe the current state of the art in biomolecular
simulation and explore the potential role of high-performance computing technologies
in extending current capabilities. Efforts within our own lab to develop novel architectures
and algorithms to accelerate molecular dynamics simulations by several orders of
magnitude will be described, along with work by other researchers pursuing alternative
approaches. If such efforts ultimately prove successful, one might imagine the emergence
of an entirely new paradigm in which computational experiments take their place
alongside those conducted in "wet" laboratories as central tools in the quest to
understand living organisms at a molecular level, and to develop safe, effective,
precisely targeted medicines capable of relieving suffering and saving human lives.
December 7th
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Dr. Kronstadt was graduated from Brown University in 1967, and received his Ph.D.
in mathematics from Harvard University in 1973. He was T. H. Hildebrandt Assistant
Professor of mathematics at the University of Michigan from 1973 to 1978, where
he conducted research in the area of several complex variables and functional analysis.
He joined the Computer Science department of the IBM T. J. Watson Research Center
in 1978. From 1978 to 1983 he helped develop software and architectural extensions
for the Yorktown Simulation Engine (YSE). In 1983, he joined the VLSI Systems group,
and became manager of that group in June 1983. In that capacity he was involved
in the design and specification of a number of high performance experimental RISC
microprocessors, as well as the development of a standard cell design system. From
1986 to 1988 he was manager of the Microsystems, Analysis and Design Department
with responsibility for experimental microprocessor design, advanced VLSI chip design,
and circuit design and analysis tools. After an assignment to the Research Division
Technical Planning Staff, he became manager of the RISC Systems Department in January,
1990. Subsequently he was named Director of Advanced RISC Systems in January, 1994,
Director of Personal Systems Solutions in May, 1995. Responsibilities in these positions
included, PowerPC based architecture, microprocessor design, compilers and operating
systems, the IBM Anti-virus product, development of advanced handwriting recognition
techniques and prototypes, development of MPEG encoding and decoding hardware and
software, and the development of wireless and mobile computing environments. In
1996, Dr. Kronstadt became Director of VLSI Systems where his responsibilities continue
to include development of the PowerPC architecture, research in microprocessor implementation
and micro-architecture, as well as CAD development. Since 2004, he has been Director
of Exploratory Server Systems and the Director of the Deep Computing Institute,
with responsibility for advanced operating systems research, highly performance
computing architectures including BlueGene, and emerging high performance applications
including computational biology. Dr. Kronstadt is a member of the IBM Academy of
Technology and was awarded two IBM Outstanding Technical Achievement awards for
his work on the YSE software. He holds three patents in microprocessor design, and
is a Fellow of the IEEE.
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Eric Kronstadt
IBM Academy of Technology
Tools of the Trade: The next Generation of Supercomputers
Abstract:
By the end of the next decade projections point to consumer "appliances" with nominal
compute capability equivalent to high end supercomputers of today and supercomputers
with raw performance capabilities approaching three orders of magnitude more powerful
than today's fastest supercomputers. Of course projections this far out in time
must always be taken with several grains of salt. In this talk I will try to say
something sensible about them. Are the projections achievable? How might they be
achieved? And, more importantly what might we do with these capabilities? (i.e.
So what?)
December 7th
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Professor Johnson was awarded a Young Investigator's (FIRST) Award from the NIH in 1992,
the NSF National Young Investigator (NYI) Award in 1994, and the NSF Presidential Faculty
Fellow (PFF) award from President Clinton in 1995. In 1996 he received a DOE Computational
Science Award and in 1997 received the Par Excellence Award from the University of Utah Alumni
Association and the Presidential Teaching Scholar Award. In 1999, Professor Johnson was
awarded the Governor's Medal for Science and Technology from Governor Michael Leavitt. In
2003 he received the Distinguished Professor Award from the University of Utah.
In 2004 he was elected a Fellow of the American Institute for Medical and Biological
Engineering (AIMBE) and in 2005 he was elected a Fellow of the American Association for
the Advancement of Science (AAAS).
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Christopher Johnson
Director, Scientific Computing and Imaging Institute, Utah University
Computational Bioimaging and Visualization:
Challenges and Opportunities
Abstract:
The next decades will see an explosion in the use and the scope of biological imaging
and the fuel for this fire will be computing and visualization. In my opinion, advanced,
multimodal imaging techniques, powered by new computational methods, will change
the face of biology and medicine. Advances in computational modeling, imaging, and
simulation allow researchers to build and test models of increasingly complex phenomena
and thus to generate unprecedented amounts of data. These advances have created
the need to make corresponding progress in our ability to understand large amounts
of data and information arising from multiple sources. In fact, to effectively understand
and make use of the vast amounts of information being produced is one of the greatest
scientific challenges of the 21st Century. Increases in imaging and computation
offer views of biological complexity in progressively greater depth and detail,
while such visualizations gradually become cheaper, faster, and easier to use. In
this talk, I will present I will provide several examples of state-of-the-art computational
bioimaging and visualization research and then go on to discuss future research
challenges and opportunities.
December 8th
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Jeremy Smith has led research groups in biomolecular simulation in three different
countries: first a 15-strong group in Paris at the French Atomic Energy Commission,
then a 30-strong group at the University of Heidelberg in Germany, and now as Director
of the Center for Molecular Biophysics at UT/ORNL. He specializes in high-performance
computer simulation and neutron scattering experiments on protein dynamics. He is
the author of over 200 papers in these fields. A press reports on his appointment in
Tennessee can be found at http://www.tennessee.edu/news/article.php?id=3692.
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Jeremy Smith
Director of the Center for Molecular Biophysics, UT/ORNL
Dynamics of Protein Binding, Reaction and Structural Change
Abstract: TBA
December 8th
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Dr. Yewdell is Chief of the Cellular Biology Section, Laboratory of Viral Diseases
in the National Institute of Allergy and Infectious Diseases.
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Jonathan W. Yewdell
National Institute of Allergy and Infectious Diseases
Gained in Translation: The Immunoribosome Hypothesis of Immunosurveillance
Abstract:
The major histocompatibility complex (MHC) class I immunosurveillance system plays
a critical role in host defense to intracellular pathogens and tumors. In 1996,
to explain the rapid presentation of viral proteins to CD8+ T cells, Jack Bennink,
Luis Anton and I proposed that peptides presented by MHC class I molecules derive
from defective ribosomal products (DRiPs), which we defined as polypeptides arising
from in-frame translation that fail to achieve native structure owing to inevitable
imperfections in transcription, translation, post-translational modifications or
protein folding. Based on evidence accrued over the past decade, it appears that
DRiPs are the the predominant source of class I peptid ligands generated from viral
and cellular proteins. In this talk I will discuss this evidence, the recent controversy
over the fraction of newly synthesized proteins that are rapidly degraded by proteasomes,
and will add a new twist to the DRiP hypothesis that posits that cells possess specialized
machinery,possibly in the form of 'immunoribosomes', to couple protein synthesis
to antigen presentation.
Bio:
I grew up in Eastchester, NY, just a few miles from New York City (well, the Bronx
anyway). I majored in biochemistry at Princeton University, graduating in 1975.
I got hooked on research during my senior thesis with Arnie Levine, who had me studying
immune rejection of adenovirus transformed cells. Though our approach was hopelessly
naive (reverberations of Z & D's discovery in Australia had yet to hit), I developed
an interest in immune recognition of virus-infected cells that would become the
major focus of my Ph.D. dissertation and career. I owe a lot to Art Levinson, then
a Ph.D. student, who took me under his wing and conveyed his boundless enthusiasm
for science and the importance of critical thinking. I obtained my Ph.D. in 1981
from the University of Pennsylvania. I worked with Walter Gerhard at the Wistar
Institute, who was the first to generate anti-viral monoclonal antibodies. I contributed
to Walter's grand project of antigenic mapping of influenza virus hemagglutinin
with monoclonal antibodies, and also generated and characterized monoclonal antibodies
to other viral proteins. During the same period, I managed to learn as little medicine
as possible to meet the requirements for a M.D. degree (1981). A one-year post-doc
at Imperial College (London, UK) with David Lane, the co-discoverer of p53 (along
with Arnie Levine [small world!]) taught me the importance of cell biology and particularly
the power of microscopy. Returning to the Wistar Institute as a newly minted Assistant
Professor in 1983, I re-initiated the collaboration with Jack Bennink (also on the
Wistar faculty by then) that began in 1981 when we provided the 1st demonstration
of CTL recognition of internal proteins of a non-transforming virus. We mapped the
influenza virus antigens recognized by mouse CTLs, and provided the initial description
of immunodominance at the level of individual viral gene products. At the same time
I was using mAbs to study the conformational alterations in flu HA during viral
penetration and HA biogenesis. Our last discovery at Wistar was that the cytosol
is the portal to the class I processing pathway. In 1987, Jack and I were recruited
by Bernie Moss to NIAID where we set up a joint lab, first in a new satellite facility
in Rockville, moving four years later to the main campus in Bethesda. We were fortunate
to attract the first of what would become a wonderful group of hard working and
talented post-doctoral fellows. In Rockville, our team discovered the effects of
brefeldin A on Golgi to ER trafficking and antigen presentation, the lack of COOH-terminal
trimming of antigenic peptides, and the ability of viral proteins to block antigen
presentation. In Bethesda, we discovered NH2-terminal trimming of peptides in the
ER, the role of DRiPs in generating antigenic peptides, the contribution of the
myriad factors that contribute to immunodominance, the dependence of cross-priming
on proteasome substrates, the involvement of the ubiquitin-proteasome pathway in
HIV morphogenesis, and PB1-F2, the 11th influenza A virus gene product.
I am extremely grateful to NIAID for paying me to do a job I would do for free had
I invested early in Enron and sold at just the right time.
December 8th
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Dr. Altshuler's laboratory aims to characterize and catalogue patterns of human genetic variation,
and to apply this information to understand the inherited contribution to common diseases. Dr.
Altshuler was a leader in the SNP Consortium and International HapMap Consortium, public-private
partnerships that created genome-wide maps of human genetic diversity that now guide the design
and interpretation of genetic association studies. Dr. Altshuler's group has also contributed to
identifying the role of common genetic variants in type 2 diabetes, prostate cancer, and lupus.
Dr. Altshuler is a Clinical Scholar in Translational Research of the Burroughs Wellcome Fund,
a Charles E. Culpeper Medical Scholar, and winner of the Stephen Krane Award of the
Massachusetts General Hospital. He received the Richard and Susan Smith Pinnacle
Award of the American Diabetes Association, and the "Freedom to Discover"
Award from the Foundation of Bristol-Myers Squibb. He is a member of
Advisory Boards at The National Institutes of Health, The Doris Duke Charitable
Foundation, The Juvenile Diabetes Research Foundation, The Wellcome Trust and Merck
Research Laboratories, on the Editorial Board of Annual Reviews of Human Genetics and
Genomics, and the Board of Reviewing Editors at Science. Professor Altshuler is one
of four Founding Members and Director of the Program in Medical and Population
Genetics of The Broad Institute of Harvard and MIT, a unique research collaboration
of Harvard, MIT, The Whitehead Institute, and the Harvard Hospitals.
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David Altshuler
Broad Institute of Harvard and MIT
Human Genome Sequence Variation and the inherited Basis of Disease
Abstract:
Despite great progress in medical science much remains to be learned about the pathophysiological
processes that underlie disease risk in the general population, and to identify
those genes whose products, if modulated by a therapeutic intervention, might effectively
prevent or treat disease. As family history is one of or the strongest risk factor
for nearly all human diseases, and given great progress in knowledge of and tools
for studying the human genome, human genetics offers a promising approach to expand
our knowledge of human diseases mechanisms. Until recently, studies of human genetics
were limited to family-based linkage studies, and to candidate gene association
studies, neither of which have proven generally successful in studies of complex,
common diseases. While linkage studies were genome-wide, and thus could discover
novel information about disease mechanisms, association studies were previously
limited to preconceived hypotheses about which genes might be responsible. It has
recently become possible to systematically test common genetic variants for association
to disease. The HapMap Project provides a guide for the design and interpretation
of linkage disequilibrium-based association studies. Affordable genome-wide genotyping
technologies enable whole-genome association studies in large clinical samples.
Copy number polymorphisms (CNPs) are similiarly being catalogued, and next-generation
microarray technologies make it possible simultaneously to genotype SNPs and CNPs
genome-wide. Robust and reproducible SNP associations have already provided novel
insights into common diseases such as type 1 and type 2 diabetes, prostate cancer,
age related macular degeneration, Alzheimer's disease, deep venous thrombosis, inflammatory
bowel disease, rheumatoid arthritis, and systemic lupus erythematosis, as well as
into quantitative traits such as hyperlipidemia, and QT intervals on the ECG. Whole
genome association studies in a variety of diseases will soon provide a more complete
picture of the role of common SNPs and CNPs in human disease, providing insight
into disease mechanisms, new pathways as targets for therapeutic intervention and
disease prevention, and clues about the evolutionary history of common human diseases.
December 8th
Eric Davidson, Ph.D. California Institute of Technology
Title: TBA
Abstract: TBA
John Reynders Chief Information Officer, Eli Lilly and Company
Title: TBA
Abstract: TBA
Ellen Rothenberg, PhD California Institute of Technology
Title: TBA
Abstract: TBA
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