School of Medicine
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Postdoctoral Research Fellow, Developmental Biology
Current Research and Scholarly Interests The discovery that insulin-producing ?-cells can be generated from cell sources within and outside the pancreas is of fundamental importance in terms of developing novel treatment strategies for diabetes. A major caveat to this is our relatively poor understanding of the players involved in this process and the lack of molecular characterization of the ?converted? ?-cells. This knowledge is key to our success in enhancing this process to its maximum therapeutic potential and efficiency. In this context, recent work has shown that ?-cells can be used as a source to generate ?-cells under conditions of near-total ?-cell depletion in mice. However the molecular mechanisms regulating ?-cell identity are unknown. This knowledge would allow us to harness the potential of ?-cells to give rise to ?-cells in diabetic patients where pancreatic ?-cells tend to be in abundant supply within the pancreas. My work in the laboratory has elucidated the role of two genes in maintaining ?-cell identity: Dnmt1 and Arx. Dnmt1, a DNA methyltransferase methylates DNA and is involved in gene repression. Arx is a transcription factor that is essential for ?-cell specification during embryogenesis. My work demonstrates that conditional in vivo inactivation of Dnmt1 and Arx in adult ?-cells causes them to convert into insulin producing ?-like-cells demonstrating the necessity of these two factors in maintaining ?-cell fate. Further functional characterization of these ?converted? cells will elucidate the extent to which ?-to- ?-cell conversion has occurred in these animals. I am also assessing the individual contributions of Dnmt1 and Arx in maintaining adult ?-cell identity.
James K. Chen
Professor of Chemical and Systems Biology and of Developmental Biology and, by courtesy, of Chemistry
Current Research and Scholarly Interests Our laboratory combines synthetic chemistry and developmental biology to investigate the molecular events that regulate embryonic patterning, tissue regeneration, and tumorigenesis. We are currently using genetic and small-molecule approaches to study the molecular mechanisms of Hedgehog signaling, and we are developing chemical technologies to perturb and observe the genetic programs that underlie vertebrate development.
Department of Pathology Professor in Experimental Pathology and Professor of Developmental Biology
Current Research and Scholarly Interests Chromatin regulation and its roles in human cancer and the development of the nervous system. Engineering new methods for studying and controlling chromatin in living cells.