Dartmouth Life Sciences Symposium History: 2012
2012: Alternative Protein Confirmation in Biology and Disease
Moderators
Patrick Dolph, Ph.D. and Surachai Supattapone, M.D., Ph.D., D.Phil
Speakers
Susan Lindquist, Ph.D.
"An Unexpected Discovery Platform for Neurodegenerative Diseases"
Professor of Biology, MIT; Member, Whitehead Institute for Biomedical Research
Investigator, Howard Hughes Medical Institute
Susan Lindquist is a pioneer in the field of protein folding. Her work has provided transforming insights on the role of protein folding in the evolution of new traits and the devastations of human disease. Her seminal work on the role of Hsp90 in folding mutant oncogenic kinases lead to the development of Hsp90-based therapeutics. Her work in fruit flies, mustard plants and yeast established that Hsp90 pervasively influences the manner in which genotypes are read out into phenotypes by chaperoning the folding of key players in signal transduction pathways. This work provided the first explanation for the rapid evolution of complex traits in response to environmental stress. She established the biochemical basis of protein-based inheritance in yeast and created a new understanding of amyloid protein function and assembly. Most recently, her group has developed new platforms for dissecting the protein-folding problems that drive neurodegenerative diseases, with an aim of discovering new therapeutic strategies based on stopping the precipitating causes of such protein-folding disorders. Susan Lindquist is a Member and former Director of the Whitehead Institute, and is an Investigator of the Howard Hughes Medical Institute. She is a member of the National Academy of Sciences, the American Academy of Arts and Science, the American Philosophical Society, and the Institute of Medicine. Her honors also include the Dickson Prize in Medicine, the Otto-Warburg Prize, the Genetics Society of America Medal, the FASEB Excellence in Science Award, the Max Delbrueck and the Mendel Medals. In 2009, she was the recipient of the National Medal of Science. Susan Lindquist is also a member of the Board of Directors of Johnson & Johnson, and a co-founder of FoldRx, a biotech company (recently acquired by Pfizer) that develops drug therapies for diseases of protein misfolding and amyloidosis. Dr. Lindquist received her PhD in Biology from Harvard University, and was a postdoctoral fellow of the American Cancer Society at the University of Chicago.
Arthur L. Horwich, M.D.
"Chaperonin-mediated Protein Folding and Beyond"
Sterling Professor of Genetics and Professor of Pediatrics, Yale University
Investigator, Howard Hughes Medical Institute
Art Horwich grew up in Chicago, attended Brown University's 6 year medical program, then trained in pediatrics at Yale School of Medicine. He carried out postdoctoral training first at the Salk Institute, working on viral transformation with Walter Eckhart and Tony Hunter, and then worked on the mitochondrial urea cycle enzyme OTC with Leon Rosenberg in Genetics at Yale. He moved across the hall from Rosenberg as a junior faculty person and embarked on studies of yeast mutants affecting the machinery of mitochondrial protein import. One such mutant affected the folding of newly imported proteins, as shown in collaboration with Ulrich Hartl, and involved a large assembly dubbed Hsp60. Subsequent studies with Ulrich, with Yale colleague Paul Sigler, with Helen Saibil at Birkbeck College, and with Kurt Wuethrich, have led to an understanding of how the homologous bacterial chaperonin system, GroEL/GroES, mediates protein folding. In further studies, a model of protein misfolding-induced neurodegeneration, namely SOD1-induced ALS, is being investigated in transgenic mice using a variety of approaches. Among his honors, Dr. Horwich is a member of the National Academy of Sciences and received both the Rosenstiel Award and the Lasker Award jointly with Dr. Hartl. He is currently the Sterling Professor of Genetics and Professor of Pediatrics at Yale University and an investigator of the Howard Hughes Medical Institute.
Reed B. Wickner, M.D.
"Biology and Structure of Yeast Prions: How a protein can be a gene"
Chief, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Reed Wickner received his BA at Cornell in mathematics and MD from Georgetown University School of Medicine. Dr. Wickner did postdoctoral research with Herb Tabor at NIH studying enzymology, and then with Jerry Hurwitz at Albert Einstein studying DNA replication. He began his independent work at NIH studying the genetics of dsRNA viruses in S. cerevisiae. In 1994, he discovered that yeast have prions, infectious proteins analogous (but not homologous) to the mammalian PrP-based disease agents. He showed that proteins can act as genes, and that the prion amyloids (filamentous protein polymers) have an in-register parallel beta sheet structure that can explain how proteins can template their conformation (just as DNA templates its sequence), explaining their ability to serve as genetic material. Recently his group has investigated the biological roles of yeast prions, finding that the prions [PSI+] and [URE3] can be lethal, and even their mildest forms are detrimental to yeast. Dr. Wickner is a member of the National Academy of Sciences and is currently the Chief of the Laboratory of Biochemistry and Genetics at the National Institute of Diabetes and Digestive and Kidney Diseases.
Richard I. Morimoto, Ph.D.
"Stress Responses and Chaperone Networks in Biology, Aging, and Disease"
Bill and Gayle Cook Professor of Biology
Director, Rice Institute for Biomedical Research, Northwestern University
Richard Morimoto is the Bill and Gayle Cook Professor of Biology and Director of the Rice Institute for Biomedical Research at Northwestern University. He holds a BS from the University of Illinois at Chicago, PhD in Molecular Biology from The University of Chicago, and did postdoctoral research at Harvard University in Cambridge, MA. His research has been on the heat shock response, the function of molecular chaperones, and the role of proteostasis to maintain the stability of the proteome in health and in the face of stress, aging and diseases of protein conformation. These studies provide a molecular basis for the mechanisms that maintain the stability of the proteome in health and the basis of age-associated diseases including neurodegeneration, metabolic diseases, and cancer. Morimoto has published over 225 papers and edited four books. He has received many academic honors and awards including two MERIT awards from the National Institutes of Health and elected membership in the American Academy of Arts and Sciences. Dr. Morimoto has been continuously funded by the NIH, the Huntington Disease Society of America, the ALS Association, the American Cancer Society, the Ellison Medical Foundation and the Daniel F. and Ada L. Rice Foundation. He is on many Scientific Advisory Boards including the University of Heidelberg, RIKEN Brain Science Institute, Roswell Park Cancer Institute, BioCity Turku, Max Planck Institute, the Zilkha Neurogenetics Institute at USC, and Argonne National Laboratory. He is a co-founder of Proteostasis Therapeutics, Inc. a biotech company recently formed in Cambridge, MA to discover small molecule therapeutics for diseases of protein conformation.
Patrick J. Dolph, Ph.D.
"Photoreceptor Cell Death Triggered by Mislocalized Aggregated Rhodopsin"
Associate Professor of Biological Sciences, Dartmouth College
Patrick Dolph received his BS in Biology from Oregon State University and his PhD in Medical Sciences from New York University Medical Center. He did postdoctoral research at University of California at San Diego. Dr. Dolph joined the Dartmouth faculty in 1995 and was the recipient of a Pew Scholars Award in the Biomedical Sciences. He is currently an Associate Professor of Biological Sciences at Dartmouth. Dr. Dolph's laboratory utilizes Drosophila melanogaster as a model system to study the molecular mechanisms of cell death associated with neuronal and retinal degeneration. Much of his work has focused on a cell death pathway that is initiated by the rapid internalization of rhodopsin and its subsequent aggregation in the endosomal system. The misfolded rhodopsin triggers a novel cell death pathway that is independent of caspases and other classic apoptotic proteins, but instead involves innate immunity signaling and the eventual activation of the transcription factor NF-κB.
Surachai Supattapone, M.D., Ph.D., D. Phil.
"Role of Cofactors in Prion Propagation"
Professor of Biochemistry and Medicine, The Geisel School of Medicine at Dartmouth
Surachai Supattapone received his BS in Chemistry, PhD in Neuroscience and MD from Johns Hopkins University, and his DPhil in Physiology from Oxford University as a Rhodes Scholar. He completed his medical residency in Internal Medicine at the Massachusetts General Hospital and his clinical and postdoctoral research fellowships in Infectious Diseases at the University of California, San Francisco. Dr. Supattapone joined the faculty of Geisel School of Medicine at Dartmouth in 2001, where he is currently a Professor of Biochemistry and Medicine. He and his colleagues are studying the pathogenesis of prion diseases using unique biochemical and genetic model systems. Notable achievements of Dr. Supattapone's laboratory include the identification of cofactors required for infectious prion propagation in vitro, production of infectious prions from a minimal set of purified components, the first demonstration that infectious prions could be produced in vitro, and the demonstration that cofactor molecules regulate prion infectivity and strain properties. Dr. Supattapone has been the recipient of the David Israel Macht Award for Basic Science at the Johns Hopkins School of Medicine, the Burroughs Wellcome Career Development Award, and the Junior Faculty Award for Basic Science at the Geisel School of Medicine.