Seminars: Spring 2013
Michele Markstein, Ph.D.
Assistant Professor of Biology, UMASS, Amherst
"Cancer Stem Cells: Getting Their Fix”
Research Summary: The Markstein laboratory uses the fruit fly Drosophila melanogaster to identify drugs and drug targets that can block the growth of cancer stem cells in vivo. Drosophila may seem like an odd choice because fruit flies do not get cancer in the wild. However, in the lab we can build tumor models in flies that have many features in common with mammalian cancers. This is a powerful approach because it enables us to perform large-scale cancer screens in vivo on a scale that is not feasible in mammals. In her talk, Dr. Markstein will discuss a tumor model that she created by mis-expressing a human RAF oncogene (a gene that causes cancer in humans) in the adult fly intestine. She will show how she has used this model to identify drugs with anti-cancer activity as well as genes required by tumor cells. When tumor cells depend on certain genes for their survival, they are said to be “addicted” to those genes. She is now focusing on identifying “epigenetic addictions” of tumor cells —genes required by tumor cells to turn genes on and off across the genome. [Host: Rachel Levin]
Mary Gehring, Ph.D.,
Member, Whitehead Institute, Assistant Professor of Biology, MIT
“Epigenetic Reprogramming during Plant Reproduction"
Research Summary: DNA methylation is a heritable epigenetic mark important for genome stability, gene imprinting, and transposable element silencing in diverse eukaryotes. During reproductive development in plants the DNA methylation landscape is dramatically altered in one of the female gametes. Short transposable elements are actively demethylated. Since the expression of some genes is tied to the epigenetic status of nearby transposable elements, the resultant epigenetic asymmetry between maternal and paternal alleles can create imprinted gene expression in the seed after fertilization. Through whole genome methylation and expression profiling, the Gehring lab is using natural genetic and epigenetic variation within the Arabidopsis thaliana species to test the hypothesis that transposable elements drive genomic imprinting and to identify imprinted genes that may underlie various seed traits. [Host: Richard Goldsby]
R. Scott Stephens '99, M.D.
Assistant Professor of Medicine, Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University
"Kinase-Mediated Regulation of Lung Endothelial Antioxidant Function"
Research Summary: Dr. Stephens’s research interest is in acute lung injury, a common and often lethal condition. Specifically, he has focused on the pulmonary endothelium: the cell layer which lines the blood vessels in the lungs, and the regulation of endothelial antioxidants and endothelial permeability via protein kinase signaling. Using primary isolated mouse lung endothelial cells, the isolated perfused mouse lung, knock-out mice, and intact animal models, he has shown that activation of Protein Kinase G by cGMP increases levels of antioxidants in pulmonary endothelium, leading to increased resistance to oxidant-mediated acute lung injury. Most recently, he has described a novel interaction between PKG and the c-Abl tyrosine kinase, and have found that inhibition of c-Abl also attenuates oxidant-induced lung injury. His long-term goal is to develop new approaches to treating patients with acute lung injury and improve the outcomes of patients with this condition. [Host: Dominic Poccia]
Cammie Lesser, M.D., Ph.D.
Associate Professor of Medicine, Department of Microbiology and Immunology, Harvard Medical School "Rising to the Challenge: Yeast Functional GenomicsProvides Insights into Bacterial Pathogenesis”
Research Summary: Many Gram-negative bacteria, including pathogens and endosymbionts, directly usurp eukaryotic host cell processes to promote their own survival and spread by injecting tens of proteins directly into host cells using complex secretion systems. The Lesser lab focuses on identifying the secreted substrates and determining their roles in pathogenesis, particularly of type 3 secretion systems which are common to gastrointestinal pathogens. For these studies, they pioneered the development of the yeast Saccharomyces cerevisiae as a model system for studying mechanisms of bacterial pathogenesis and they developed a novel and powerful assay for studying protein-protein interactions in live cells, the Protein Interaction Platform assay. These studies have not only provided new insights into bacterial and host cell biology, but they have also identified new avenues for the development of novel antimicrobial agents. [Host: Caroline Goutte]
Alan Blum '69, M.D.,D.Sc.
Amherst College Honorary Degree Recipient ‘06; Professor, Gerald Leon Wallace Endowed Chair Department of Family Medicine University of Alabama School of Medicine
"Blowing Smoke: The Lost Legacy of the Surgeon General's Report on Smoking and Health.”
Research Summary: It has been nearly half a century since President John F. Kennedy commisisoned Surgeon General Luther Terry and ten scientists to evaluate the scientific evidence on smoking and health. The committee's landmark report was a scathing indictment of cigarettes and launched the modern anti-smoking movement. But although we have now learned through internal tobacco industry documents that cigarette companies conspired for decades to dismiss the dangers of smoking, troubling questions linger: What did the public health community know about the impact of smoking on health? When did they know it? And what did they do about it? [Hosts: the Croxton Lecture Fund, Steve George, and the AC Lecture Committee.] Dr. Blum's Gallery Talk at the Mead Art Museum.
Stephen Devoto, Ph.D.
Professor, Biology Department, Neuroscience and Behavior Program, Wesleyan University
“Muscle and Stem Cell Development in Zebrafish”
Research Summary: The Devoto lab is interested in the development of muscle and muscle stem cells as part of a broader goal of understanding the cellular and molecular mechanisms that lead to the development of specific identities during development. They use zebrafish as a model for all vertebrates, including humans, because zebrafish are readily accessible for experimental manipulations throughout development and because a genetic approach to studying development is feasible. Muscle is a very abundant and easily accessible tissue, and diseases of muscle development are debilitating and common childhood diseases. Vertebrate muscle precursors derive from a transient embryonic tissue known as the dermomyotome. The development of the dermomyotome and the morphogenesis of the myotome take place within the somites, epithelial segments of the paraxial mesoderm. They have recently identified a transcription factor, Tbx6, as an important regulator of dermomyotome development. Tbx6 also regulates somite formation, and they are now examining other genes that regulate somite formation and interact with Tbx6. They hope to understand the gene regulatory network that regulates muscle and muscle stem cell development in the early embryo. [Host: Josef Trapani]
Charles Ross, Ph.D.
Assistant Professor of Evolutionary Biology, Hampshire College
“The Particular and Personal of Speciation"
Research Summary: Charles L. Ross, Assistant Professor of Evolutionary Biology at Hampshire College, received his B.S. and M.S. in biology from Stanford University, and his Ph.D. in ecology and evolutionary biology from Cornell University. He did postdoctoral work at the University of Arizona and New Mexico State University. Charles studies the ecological and evolutionary genetics of hybrid zones and speciation, specifically in crickets. His research and teaching interests include all aspects of evolutionary biology, as well as population genetics, molecular ecology, entomology, and genomics. [Host: Bill Zimmerman]
David M. Margulies, M.D.
Executive Director of the Gene Partnership at Children’s Hospital in Boston (CHB) and Faculty Member of the Division of Developmental Medicine, the Center for Biomedical Informatic, and the Division of Genomics at the Harvard Medical School.
Research Summary: David M. Margulies is senior associate in medicine and director of The Gene Partnership (TGP) at Children's Hospital Boston, a large-scale effort that melds genomic, medical record, and personal data into one comprehensive system. His career successfully straddles academic and commercial enterprise, having both practiced medicine and developed computing systems that support physicians. He founded a number of companies, including, most recently, Correlagen Diagnostics, Inc., (acquired by LabCorp), which developed an integrated platform for diagnostic evaluation of human genetic variation. He also served as chief information officer at Children's, director at Ixion Corporation, and executive vice president and chief scientist at Cerner Corporation. Margulies earned his M.D. from Harvard Medical and completed his residency in internal medicine at Columbia University's College of Physicians and Surgeons. biology from Stanford University, and his Ph.D. in ecology and evolutionary biology from Cornell University. Dr. Margulies is the 2013 Amherst College Croxton Lecturer. [Host: Michael Hood.]
24 February 2015 TLR