THE CHA LAB

Biologic sex has pleiotropic influences across multiple facets of physiology such as cognition, immunity, and metabolism. However, robust mechanistic studies evaluating the contributions of biologic sex on non-gonadal tissues to influence human health remain unclear. The Cha lab strives to understand the intersection of reproduction and metabolism by probing a unique model of extreme sex dimorphism in a fundamental aspect of metabolism: glycemia. Familial carriers of a pathogenic genetic mutation manifest remarkably dimorphic phenotypes: men are vulnerable to dysglycemia (diabetes) while women are predisposed towards insulin-producing tumors (hypoglycemia) - two divergent diseases resulting from the same mutation, based solely on biologic sex!

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 to produce sweeping sex differences will uncover novel directives and fill critical gaps in our understanding of how biologic sex influences metabolism in our ongoing efforts towards precision medicine.