Michael Kalwat

Investigating insulin hypersecretion and β-cell heterogeneity to identify therapeutics for diabetes and rare diseases.

Hypersecretion of insulin is a feature of multiple diseases, including diabetes and congenital hyperinsulinism. The Kalwat lab is focused on identifying mechanisms that regulate the responses of pancreatic islet β-cells to hypersecretion and discovering novel modalities to suppress pathological insulin secretion to protect β-cell function. To accomplish this, we apply a variety of cell-based assays (e.g. insulin secretion, Ca2+ influx), chemical biology (e.g. small molecules, peptide synthesis) and disease model systems. β-cells are also heterogeneous between humans and within islets, but distinct subpopulations of β-cells have not been well-characterized. We are applying machine learning methods to uncover markers of these β-cell subsets followed by validation (e.g. spatial transcriptomics) and functional assays with the goal of defining new biology and development of new drugs.