Current Projects

Sex differences are recognized in metabolism but poorly understood. Families in which carriers of the S64F MAFA variant manifest extreme sex dimorphism in which men are prone to diabetes while women succumb to β cell tumors (insulinomas) and refractory hypoglycemia. Our mouse model remarkably phenocopies this extreme condition, which is largely independent of adult sex hormones. This model is a rare tool to molecularly interrogate underlying sex differences in a critical metabolic cell type and provide insights into how sex differences manifest in physiology and disease states.

Using a model of a rare form of monogenic diabetes (S64F MAFA), we have shown that diabetes in males is associated with widespread accelerated pancreatic islet β cell senescence and aging - features noted in type 1 and type 2 diabetes. This project will exploit this model to understand mechanisms underlying accelerated β cell senescence and evaluate the utility of senolytics in the treatment or prevention of β cell dysfunction.

Embryonic diapause is an alternative reproductive strategy defined by the temporary arrest in blastocyst growth within a synchronously quiescent uterus to temporally uncouple conception from parturition until conditions are favorable for the survival of the mother and newborn. Pathways activated in maintaining diapause counter those in cellular aging and provide insights into novel anti-aging strategies.