Fred S. Gorelick, M.D.

Professor
Section of Digestive Diseases and Cell Biology

Research Interests

My academic interest focus on the function of the exocrine pancreas. Two areas of research are pursued in our laboratory.

Pancreatitis may be initated in vivo bysupraphysiologic concentrations of acetylcholine or cholecystokinin. Similarly, supraphysiologic concentrations of these agents result in enzyme activation and not exocytosis in isolated acinar cells.

First, the mechanisms residing within the acinar cell that initiate pancreatitis are studied in cellular models of the disease. Many forms of pancreatitis appear to begin with the premature activation of pancreatic digestive enzymes within the acinar cell. We have found that this activation takes place in a special cellular organelle that has features of both a lysosome and classic secretory vesicle. We are characterizing this novel compartment and the second messenger signals that stimulate zymogen activation.

My second area of study examines the factors that regulate the movement of newly synthesized protein in gastrointestinal epithelial cells. Disordered protein movement is now recognized as a basis of a growing number of diseases including some forms of cystic fibrosis, hyperlipidemia, and alpha-1-antitrypsin deficiency. We have discovered a novel protein (Sec31m) that is the final member of the COPII protein coat that mediates vesicle movement between the endoplasmic reticulum and Golgi Complex. We are studying the role of Sec31m isoforms in moving specific cargo between these compartments. Our laboratory uses a variety of cell and molecular biology techniques including immunofluorescence microscopy, cloning and cellular transfection, protein purification, and antibody generation.

Selected publications:

• Grady T, Mah'Moud M, Otani T, Rhee S, Lerch MM, Gorelick FS. (1998) Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury. Am. J. Physiol. 38: G1010-1017.
• Otani T, Chepilko SM, Grendell JH, Gorelick FS. (1998) Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis. Am. J. Physiol. 275: G999-G1009.
• Shugrue CA, Kolen ER, Peters H, Czernik A, Kaiser C, Matovcik L, Hubbard AL, Gorelick F. (1999) Identification of the putative mammalian orthologue of Sec31P, a component of the COPII coat. J. Cell Sci. 112: 4547-4556.
• Gorelick FS and Shugrue C. (2001) Exiting the endoplasmic reticulum. Mol. Cell Endocrinol. 177: 13-18.
• Lu Z, Karne S, Kolodecik T, and Gorelick F.(2002) Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells. Am. J. Physiol. Gastrointest. Liver Physiol. 282: G501-G507.
• Gorelick F, Topazian M, and Pandol S. (2002) Pancreatic physiology and pancreatitis. AGA Graduate Teaching Program, slide set and syllabus (In Press, October 2002).
• Topanzian M and Gorelick F. (2002) Acute Pancreatitis in Textbook of Gastroenterology. Ed. T. Yamada, D.Alpers, C. Owyang, D. Powell, F. Silverstein, Lippincott, Philadelphia.

Contact

Campus Address
Department of Internal Medicine
GI Research Laboratory
Building 27
VA HealthCare Connecticut
950 Campbell Avenue
West Haven, CT 06510

E-mail
fred.gorelick@yale.edu