Beta-cell Biology and Regenerative Medicine

In the Chemical Biology program, we are working towards the discovery of small-molecule therapeutics for the treatment of type-1 diabetes that target the biology of human beta cells. A central feature of this project area is our reliance on human primary islets and their derived cells from donors. We aim to develop in vivo therapies for type 1 diabetes that act by increasing the number or function of pancreatic beta cells. Overall, we have taken two approaches:

Unbiased phenotypic cell-based assays and follow-up chemistry to identify small-molecule inducers of:

• human beta-cell proliferation
• lineage reprogramming of pancreatic alpha cells or exocrine cells to beta cells
• protection of beta cells from cytokine-induced apoptosis

Targeted gene expression-based screens to:

• control regulation of pancreatic cell fate and cell number
• achieve small-molecule control of specific chromatin marks

This work is done with support from the Juvenile Diabetes Research Foundation (JDRF) and a National Institute of Health (NIH) Type 1 Diabetes Pathfinder Award.