Islet Function & Insulin Signaling

We currently have two lines of research relevant to diabetes. On the one side, we are developing fluorescent biosensors to image and elucidate the activity architecture of insulin receptor signaling. Insulin and insulin receptor (IR) are involved in metabolism, proliferation, and differentiation. In mammals, two isoforms (IR-A and IR-B) exist due to differences in alternative splicing. Moreover, IGF1R (Insulin Like Growth Factor 1 Receptor) crosstalks with insulin and insulin receptor. IR and IGF1R function as dimers so there are several hybrid receptors formed by IR and IGF-1R. We are developing tools to study the cell signaling of these receptors.

On the other side, we are developing fluorescent assays to accurately define functional quality and potency of donor and human-stem-cell-derived islets. The latter project is closely collaborated with Dr. Jose Oberholzer and Dr. Yong Wang at the UVA Charles O. Strickler Transplant Center and the UVA Microfluidic Islet Functional Analysis Facility. In addition to fluorescent protein based biosensors, we are exploring biosensors based on other imaging modalities, such as bioluminescence, with the hope of performing functional assays directly on in vivo animal models (mice and monkeys). Our goal is to advance cell replacement therapy for type 1 diabetes (T1D) based on human islets, encapsulated islets, xenogeneic islets, or stem-cell-derived islets.