Research in the Gaisano lab is focused on molecular mechanisms regulating exocytosis, employing islet cells as models. We were one of the firsts to demonstrate that SNARE proteins originally found to mediate neurotransmitter release are conserved in non-neuronal cells, including the pancreatic islet to regulate secretion. We contributed to the original work showing SNARE protein regulation of insulin granule exocytosis, and subsequently contributed much of the work showing how SNARE proteins physically and functionally interact with beta-cell ion channels (Kv, KATP, Ca2+) to regulate the intricate sequence of ion fluxes, membrane potential and exocytotic fusion events leading to secretion. Current efforts are a continuation of the above (1 and 2) plus two new directions (3 and 4). 1) SNAREs interactions with Kv and Ca2+ channels forming ‘excitosomes’ and how these excitosomes are involved in the insulin granule exocytotic machinery for predocked (first phase insulin secretion) and newcomer granules (second phase insulin secretion); and how these insights could reveal rescue strategies for T2D insulin secretory deficiency. 2) Islet alpha cell secretory mechanisms and crosstalk with beta- and delta-cells in health and their dysregulation in T1D. For these 2 directions, we are using human T1D and T2D pancreas as well as normal human pancreas. 3) Using the transparent anterior chamber of the mouse eye, we are observing the behaviour of implanted human islets, a capability that we directing at assessing human T1D and T2D islet biology over a long duration, their responses to novel treatment strategies, and also islet regenerative medicine. 4) Role of the intestinal microbiome in its contribution to the pathogenesis of the metabolic syndrome, and identifying new treatment strategies. The Gaisano lab has in place a full spectrum of state-of-the-art technologies to assess these four funded directions.