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  • Harini Chakravarthy

    Harini Chakravarthy

    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.

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