Guy Groblewski

The exocrine pancreas is responsible for the synthesis, storage and secretion of digestive enzymes that are necessary for the breakdown and assimilation of the diet. This process occurs within the functional unit of the gland known as the acinus. Hormones and neurotransmitters act on G-protein coupled receptors located on the plasma membrane, setting in motion a series of biochemical signals culminating in the exocytosis of digestive enzymes into the pancreatic duct. The main intracellular messenger mediating exocytosis is a rise in the concentration of cellular Ca2+. Under pathophysiological conditions aberrant elevations in Ca2+ both inhibit exocytosis and promote a lysosome-mediated activation of digestive enzymes marking the earliest stages of pancreatitis.  In spite of substantial advances made in understanding the mechanism(s) mediating Ca2+ mobilization, comparatively less is known of the regulatory proteins that respond to elevated Ca2+ in the cytoplasm. The major focus of this laboratory is to elucidate the precise down-stream molecular events that occur as a consequence of acutely elevated Ca2+ in secretory epithelia. Elucidation of Ca2+-signaling pathways in pancreas is essential to understand the pathophysiology of acute pancreatitis and pancreatic cancer.