School of Medicine

Showing 1 of 1 Results

  • Harini Chakravarthy

    Harini Chakravarthy

    Postdoctoral Research Fellow, Developmental Biology

    Current Research and Scholarly Interests The discovery that insulin-producing β-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’ β-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 α-cells can be used as a source to generate β-cells under conditions of near-total β-cell depletion in mice. However the molecular mechanisms regulating α-cell identity are unknown. This knowledge would allow us to harness the potential of α-cells to give rise to β-cells in diabetic patients where pancreatic α-cells tend to be in abundant supply within the pancreas. My work in the laboratory has elucidated the role of two genes in maintaining α-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 α-cell specification during embryogenesis. My work demonstrates that conditional in vivo inactivation of Dnmt1 and Arx in adult α-cells causes them to convert into insulin producing β-like-cells demonstrating the necessity of these two factors in maintaining α-cell fate. Further functional characterization of these ‘converted’ cells will elucidate the extent to which α-to- β-cell conversion has occurred in these animals. I am also assessing the individual contributions of Dnmt1 and Arx in maintaining adult α-cell identity.