Targeting DNA Hydroxymethylation to Promote Human Beta Cell Function
Contact PI: Sangeeta Dhawan, PhD, City of Hope
Start Date: June 1, 2018
End Date: June 30, 2023
HIRN New Investigator Award Recipient
Diabetes results from reduced number of functional insulin producing beta-cells of the pancreas. Thus, one of the primary goals of strategies for diabetes treatment is replenishment of functional beta-cells. Beta-cells are formed in fetal life and acquire the ability to secrete insulin in response to changes in glucose levels upon birth. Recent studies from our group have shown that two distinct small chemical modifications of the DNA are critical for this process, and perturbations of these two modifications leads to loss of beta-cell function. The balance of these two modifications is critical for regulating cell differentiation and growth. In this proposal, we now aim to define the specific role of these modifications in regulation of beta-cell homeostasis, whether this regulatory process is impaired in beta cell dysfunction in the context of type 1 diabetes, and whether we can target this mechanism to promote beta-cell function. The proposed studies have important implications for the development of improved approaches for generating functional beta cells for diabetes therapy and the identification of new drug targets. Our studies will also provide a clearer understanding of the pathogenesis of type 1 diabetes.