The Davis Lab is interested in pancreatic beta cell biology. One area of focus is on understanding the mechanisms underlying the proliferative response in the beta cell. Beta cells are normally in a quiescent state, but can be stimulated to divide and expand in response to certain stimuli. When faced with insulin resistance and increased demand for insulin during pregnancy or in the setting of obesity, the beta cell will divide and overall beta cell mass is increased. Conversely, one of the defects in type 2 diabetes is a loss of overall beta cell mass leading to insufficient insulin production. In addition, type 1 diabetes is caused by autoimmune destruction of the beta cell, although there is evidence that a small population of beta cells may continue to attempt to replicate and expand in the setting of ongoing autoimmune attack. Understanding the mechanisms of beta cell proliferation that occur naturally in these adaptive settings may help us identify new therapeutic targets that can help drive beta cell proliferation in the patient with prediabetes, type 2 diabetes, a recent islet transplant, or potentially even type 1 diabetes in combination with immune therapies. Please see our recent review article on beta cell proliferation for more information.
A second area of interest is in beta cell apoptosis. Numerous stressors (including cytokines and endoplasmic reticulum stress) lead to increased beta cell apoptosis in early type 1 diabetes and in type 2 diabetes. We are also studying the ways that the pancreatic islet adapts to stressors and promotes beta cell survival.