My expertise involves cell signaling, protein processing, protein kinase-mediated pathways and calcium signaling.  I have been particularly interested in studying early acinar cell events in acute pancreatitis and clinically relevant processes that sensitize the pancreas to the development of disease or affect its severity. I was recently involved in a study reporting that an acidic extracellular environment sensitizes to pancreatitis responses in isolated groups of pancreatic cells (acini) and in vivo (Bhoomagaud, Gastroenterology, 2009).  Furthermore, I have several publications detailing the effects of protein kinase C (PKC)-dependent and protein kinase D (PKD)-dependent pathways in the pathogenesis of acute pancreatitis (Thrower et al., 2008, 2009, 2010). I also have extensive expertise in intracellular calcium signaling pathways (Thrower et al., 1996; 1998; 2000; 2002a; 2002b; 2003a; 2003b). Since clinical studies have recently reported that cigarette smoking alone can be a risk factor for acute and chronic pancreatitis and that its effects act synergistically with alcohol abuse, I am currently examining the effects of a major constituent of tobacco – the nitrosamine NNK (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone) -- in models of this disease. Our preliminary studies suggest that NNK causes pancreatitis responses by activating a specific nicotinic receptor. I have also found that the effects of combining alcohol with NNK with respect to pancreatitis responses are additive.  I plan to further characterize the NNK-mediated pancreatitis responses and its receptor targets in the context of alcoholic pancreatitis.

REFERENCES:

1. Thrower EC, Osgood S, Shugrue CA, Kolodecik TR, Chaudhuri AM, Reeve JR Jr, Pandol SJ, Gorelick FS. The novel protein kinase C isoforms -delta and -epsilon modulate caerulein-induced zymogen activation in pancreatic acinar cells. Am J. Physiol. 2008 Jun;294(6):G1344-53. PMCID: PMC2975015
2. Bhoomagoud M, Jung T, Atladottir J, Kolodecik TR, Shugrue C, Chaudhuri A, Thrower EC, Gorelick FS. Reducing Extracellular pH Sensitizes the Acinar Cell to Secretagogue-Induced Pancreatitis Responses in Rats. Gastroenterology. 2009 137(3):1083-92. PMCID: PMC2736307.
3. Thrower EC, Wang J, Cheriyan S, Lugea A, Kolodecik TR, Yuan J, Reeve JR Jr, Gorelick FS, Pandol SJ. Protein kinase C delta-mediated processes in cholecystokinin-8-stimulated pancreatic acini. Pancreas. 2009  38(8):930-5. PMCID: PMC2767410.
4. Thrower EC, Yuan J, Usmani A, Liu Y, Jones C, Minervini SN, Alexandre M, Pandol SJ, Guha S. A novel protein kinase D inhibitor attentuates early events of experimental pancreatitis in isolated rat acini. Am J Physiol Gastrointest Liver Physiol. 2010 Oct 14. PMCID: In process.
5. Reed AM, Husain SZ, Thrower E, Alexandre M, Shah A, Gorelick FS, Nathanson MH. Extracellular pH modulates calcium signaling in the pancreatic acinar cell. J. Biological Chemistry 2011 286(3):1919-26 NIHMSID #268552.
6. Thrower, E.C., Duclohier, H., Lea, E.J.A., Molle, G. & Dawson, A.P. (1996) The Inositol (1,4,5) Trisphosphate gated calcium channel: effect of the protein thiol reagent thimerosal on single channel activity. Biochem. J.  318, 61-66.
7. Thrower, E.C.,  Lea, E.J.A. & Dawson, A.P. (1998) The effects of free [Ca2+] on the cytosolic face of the inositol (1,4,5)-trisphosphate receptor at the single channel level.  Biochem J. 1998  330 ( Pt 1):559-64.
8. Thrower, E.C.,  Mobasheri, H., Dargan, S., Marius, P., Lea, E.J.A. & Dawson, A.P. (2000)  Interaction of luminal calcium and cytosolic  ATP in the control of type 1 Ins(1,4,5)P3 receptor channels. J. Biol. Chem 275, 36049-36055.
9. Thrower, E.C., Park, H.Y., Yoo, S.H., Ehrlich, B.E. (2002a) Effects of Chromogranin A on IP3 receptor activity. J. Biol. Chem. 277, 15801-15806.
10. Jiang, Q.X., Thrower, E.C., Chester, D.W., Ehrlich, B.E., Sigworth, F.J. (2002b) Three-dimensional structure of the type 1 inositol 1,4,5,-trisphosphate receptor at 24 Å resolution. EMBO J. Vol.  21, 3575-3581.
11. Leite, M.F., Thrower, E.C., Echevarria, W., Koulen, P., Hirata, K., Bennett, A.M.,  Ehrlich, B.E., and Nathanson, M. (2003a) Nuclear and cytosolic calcium are regulated independently. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2975-80.
12. Thrower E.C., Choe C.U., So S.H., Jeon S.H., Ehrlich B.E., Yoo S.H. (2003b)  A functional interaction       between chromogranin B and the inositol 1,4,5-trisphosphate receptor/Ca2+ channel. J Biol Chem. 278(50):49699-706.
13. 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.
14. Thrower, E.C., Diaz de Villalvilla, A.P., Kolodecik, T.R., and Gorelick, F.S. (2006) Zymogen activation in a reconstituted pancreatic acinar cell system.  Am J Physiol Gastrointest Liver Physiol. 290: G894-G902