Edwin C. Thrower, PhD.

Associate Research Scientist
Section of Digestive Diseases

Research Interests

My research focuses on premature activation of digestive zymogens within pancreatic acinar cells, a key event in the initiation of acute pancreatitis (AP). I am currently overseeing three projects. The first focuses on protein kinase C (PKC) which has been shown to have multiple roles in the regulation of both physiology and pathophysiology of the pancreas. We have shown that both PKC & and € isoforms participate in premature zymogen activation in varying degrees and at differing cellular locations. In a second project we have investigated the sensitizing effects alcohol plays in the induction of AP. We have shown that alcohol enhances zymogen activation by regulating the assembly and activity of an ATP-dependent proton pump, or vacuolar ATPase (vATPase). The vATPase is responsible for acidifying compartments and providing optimal conditions for zymogen activation. In a third and final project, we have looked at the role played by an AMP-dependent protein kinase (AMPK). Under conditions which cause cellular stress, such as those seen in AP, AMPK is activated. Our preliminary evidence suggests that AMPK may regulate vATPase assembly/disassembly thus limiting zymogen activation within the acinar cell and hence playing a protective role.

Teaching Activities

Lecturer in Molecular Biology and Biochemistry.

Administrative Activities

Member of VA West Haven CT Internal Animal Care and Use Committee (VA IACUC).

Current Collaborations

I currently collaborate with Dr. Fred Gorelick at Yale Digestive Diseases Section investigating cellular mechanisms in acute pancreatitis. In addition, I have collaborations with Dr. Stephen Pandol and Dr. Joseph Reeve at VA Greater Los Angeles Health Care system and the University of California Los Angeles investigating the role of PKC isoforms in acute pancreatitis.

Recent Publications:

• Edwin C. Thrower, Alexander P.E. Diaz de Villalvilla, Thomas R. Kolodecik, and Fred S. Gorelick (2006). Zymogen activation in a reconstituted pancreatic acinar cell system. Am J Physiol Gastrointest Liver Physiol 290: G894-G902
• Gorelick, F.S., Shugrue, C.A., Kolodecik, T.R. and Thrower, E.C. Vacuolar adenosine triphosphatase and pancreatic acinar cell function. J. Gastroenterol Hepatol. (2006) Oct 21 Suppl 3:S18-21.
• Waterford, S.D., Kolodecik, T.R., Thrower, E.C. and Gorelick, F.S. (2005) Vacuolar ATPase regulates zymogen activation in pancreatic acini. J. Biol. Chem. 280, 5430-5434.

Contact

Campus Address
Department of Internal Medicine
333 Cedar Street (LMP 1080)
New Haven, CT 06520

E-mail
edwin.thrower@yale.edu

Office Phone
(203) 932-5711 ext 3680