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2012-D-006-SUP - Abstract

Grant Information

Diabetes - Start-Up
Identification of novel epigenetic and signaling targets for promoting beta cell regeneration.
Sangeeta Dhawan, PhD
Department of Medicine/Endocrinology
Funding Status
  • Completed
  • 3 years, $70,000 per year
  • 4/1/2013 to 3/31/2016


2012-D-006-SUP - Abstract
Brief Summary
"Identification of Novel Epigenetic and Signaling Targets for Promoting Beta Cell Regeneration"

Diabetes results from an inadequate mass of functional beta cells. Such inadequacy could result from loss of beta cells due to an immune assault (Type 1) or the lack of compensation to overcome insulin resistance (Type 2). Thus, mechanisms that regulate the number of beta cells are key to understanding both the pathogenesis of diabetes and for developing therapies.

The ultimate goal of this work is to identify drug targets and develop approaches for expanding beta cell mass towards future application in therapeutics for diabetes, with special emphasis on small molecule agents for beta cell regeneration. My work aims to figure out the mechanisms that regulate beta cell aging, proliferation and regeneration.

The central hypothesis is that the age dependent decline in the ability of beta cells to regenerate results in the limited ability of the endocrine pancreas to cope with metabolic stress and immune assault. Our findings identify an enzyme Jmjd3 as a target to promote beta cell expansion even in aged cells. We show that JmjD3 and its interaction are attractive targets for modulation to promote beta cell regeneration using small molecule agents, without any need for genetic manipulation.

As several patients with diabetes require life-long insulin therapy and have a high risk of medical complications, there is an urgent need for development of effective oral medications. Thus, this project proposes to identify and validate molecular targets to promote beta cell regeneration, which will open the way for future development of oral medications towards diabetes therapy.

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