Our laboratory focuses on the cells that produce insulin, the pancreatic beta-cells. Loss, damage or dysfunction of the beta-cells causes diabetes. We explore how beta-cells arise during embryonic development, how they differentiate from the other pancreatic cell types, and what mechanisms control the turnover and function of the mature beta-cells. Together with many other groups, we outlined the pathways and the hierarchy of gene expression events that direct beta-cell genesis during embryonic development and adult regeneration. After birth, proliferation replaces neogenesis as the major source of new beta-cells and, together with the rate of apoptosis, determines beta-cell mass. Presently we are exploring the role of several G-protein coupled receptors and their ligands, and the role of placental and neural signals in beta-cell proliferation and death. At the same time, exploration of the downstream, intracellular pathways regulated by these signals has led to new insights into both physiologic mechanisms for beta-cell growth and the abnormal growth of pancreatic neuroendocrine tumors.
Our translational interests are directed towards understanding where these processes break down in type 2 diabetes, gestational diabetes, monogenic forms of diabetes (neonatal diabetes, MODY, and syndromic diabetes) and pancreatic neuroendocrine endocrine tumors and how to translate our knowledge into novel strategies for helping people with these disorders.