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β-cell Survival and Function

In conjunction with PDRC scientists working on stem cells and enhancing insulin function are PDRC researchers studying β-cell survival and function. Essentially, they look at how insulin secretion is controlled at the molecular level, and the cellular events that cause the initial damage to islets resulting in diabetes. For instance, one researcher has identified some of the earliest cues that "turn on" beta cell death, in research aimed at understanding the mechanisms that control beta cell stability

Jhala Lab

Diabetes ultimately results from an inadequate number of insulin-producing cells, often due to deviant induction of a "cellular suicide program." Dr. Jhala's laboratory has identified some of the earliest cues that initiate inflammation and lead to activation of the cell death program. The early stages of cell death involve an intricate crosstalk between important post-translational modifications of phosphorylation and ubiquitination. Since enzymes that regulate these modifications are highly amenable to pharmacologic intervention, a systematic examination of the events that regulate beta cell inflammation and death will identify new strategies for preserving insulin secreting beta cells.

The advent of stem cell research has renewed interest in cellular replacement therapies for the treatment of diabetes. Current technologies do not yield mature, transplantable insulin secreting cells, and often result in the multi-hormonal cells. Dr. Jhala's lab is also examining the molecular mechanisms that drive the miscues and hinder attainment of a distinct beta cell fate. Early efforts suggest that the miscues could be corrected by a time and stage dependent intervention using small molecule epigenetic modifiers.