THE CHA LAB

Our lab seeks to uncover novel molecular insights of pancreatic islet biology to ultimately develop personalized treatment options for patients with diabetes. Our lab studies a model of diabetes which shows marked heterogeneity in phenotype: affected men are vulnerable to diabetes while women are predisposed towards insulin-producing tumors (hypoglycemia). We have developed mouse models harboring this mutation which mimics several aspects of the clinical phenotypes and show marked differences in islet physiology including calcium handling, circadian dysregulation, and accelerated cellular aging, notable features also seen in type 1 and type 2 diabetes.

We take systems biologic approaches to integrate single cell gene expression, chromatin dynamics, and classical physiologic assays to assess the transcriptional, spatial, and functional changes differentially incurred by this mutation in a robust mouse model, in cell culture systems, and in genetically modified organoids (pseudoislets) derived from primary human donors. Evaluating how this mutation disrupts the metabolic landscape will uncover novel directives and fill critical gaps in our ongoing efforts towards precision medicine and optimization of cell-based therapies.