Personal HistoryDr. Raufman is board certified in Internal Medicine and Gastroenterology. He is a graduate of Albert Einstein College of Medicine, and trained at the University of Michigan and the National Institutes of Health. He has published more than 120 original papers and more than 20 book chapters. He is a member of the American Society for Clinical Investigation and sits on several NIH Study Sections and an FDA Advisory Panel. Dr. Raufman is the Program Director for an NIDDK T32 Training Grant, Training in Gastroenterology Research.
Dr. Raufman's primary research interest is the study of regulatory molecules and signal transduction in the gastrointestinal tract. His research, funded by both the VA and NIH, focuses on mechanisms whereby cholinergic agonists regulate gastrointestinal cell signaling and function, particularly the promoting effects of bile acids on colon neoplasia. These studies use both in vitro and in vivo colon cancer models, including transgenic animals, to evaluate molecular pathways and changes in gene expression that regulate neoplastic cell proliferation and apoptosis. Molecular pathways under investigation include post-muscarinic and post-epidermal growth factor receptor (EGFR) signaling that is mediated by ERK, PI-3kinase/AKT, and NF-kappaB. Moreover, the role of matrix metalloprotease activation in regulating release of EGFR ligands, primarily HB-EGF, in mediating activation of these signaling pathways is being explored. It is anticipated that this line of investigation will reveal novel therapeutic targets to treat colorectal cancer.
Cheng, K., Chen, Y., Zimniak, P., Raufman, J-P., Xiao, Y., Frucht, H. Functional interaction of conjugates of lithocholic acid with M3 muscarinic receptors on a human colon cancer cell line. Biochem. Biophys. Acta 1588:48-55, 2002.
Cheng, K., Khurana, S., Chen, Y., Kennedy, R.H., Zimniak, P., Raufman, J-P. Lithocholylcholine, a bile acid:acetylcholine hybrid, is a muscarinic receptor antagonist. J. Pharmacol. Exp. Ther. 303:29-35, 2002.
Raufman, J-P., Chen, Y., Cheng, K., Compadre, C., Compadre, L., Zimniak, P. Selective interaction of bile acids with muscarinic receptors: a case of molecular mimicry. Eur. J. Pharmacol. 457:77-84, 2002.
Cheng, K., Zimniak, P., Raufman, J-P. Transactivation of the epidermal growth factor receptor mediates cholinergic agonist-induced proliferation of H508 human colon cancer cells. Cancer Res. 63:6744-6750, 2003.
Khurana, S., Chacon, I., Xie, G., Yamada, M., Wess, J., Raufman, J-P., Kennedy, R. Vasodilatory effects of cholinergic agonists are greatly diminished in aorta from M3R-/- mice. Eur. J. Pharmacol. 493:127-132, 2004.
Karaolis, D.K.R., Cheng, K., Lipsky, M., Elnabawi, A., Catalano, J., Hyodo, M., Hayakawa, Y., Raufman, J-P. 3',5'-cyclic diguanylic acid inhibits basal and growth factor-stimulated human colon cancer cell proliferation. Biochem. Biophys. Res. Comm., 329:40-45, 2005.
Khurana, S., Yamada, M., Wess, J., Kennedy, R.H., Raufman, J-P. Deoxycholyltaurine-induced vasodilation of rodent aorta is nitric oxide- and muscarinic M3 receptor-dependent. Eur. J. Pharmacol. 517:103-110, 2005.
Xie, G., Drachenberg, C., Yamada, M., Wess, J., Raufman, J-P. Cholinergic agonist-induced pepsinogen secretion from murine gastric chief cells is mediated by M1 and M3 muscarinic receptors. Am. J. Physiol. 289:G521-G529, 2005.
Cheng, K., Raufman, J-P. Bile acid-induced proliferation of a human colon cancer cell line is mediated by transactivation of epidermal growth factor receptors. Biochem. Pharmacol. 70:1035-1047, 2005.
Aslinia, F., Uradomo, L., Steele, A., Greenwald, B.D., Raufman, J-P. Quality assessment of colonoscopic cecal intubation: An analysis of 6 years of continuous practice at a university hospital. Am. J. Gastroenterol. 2006 (In Press).
Cheng, K., Xie, G., Raufman, J-P. Matrix metalloproteinase-7-catalyzed release of HB-EGF mediates deoxycholyltaurine-induced proliferation of a human colon cancer cell line. Biochem. Pharmacol. 73:1001-1012, 2007.
Hamilton J.P., Xie, G., Raufman, J-P., Hogan, S., Griffin, T.L., Packard, C.A., Chatfield, D.A., Hagey, L.R., Steinbach, J.H., Hofmann, A.F. Human cecal bile acids: concentration and spectrum. Am. J. Physiol. (Gastrointest. Liver Physiol.) 293:G256-263, 2007.
Raufman, J-P., Shant, J., Guo, C., Roy, S., Cheng, K. Deoxycholyltaurine rescues human colon cancer cells from apoptosis by activating EGFR-dependent PI3K/Akt signaling. J. Cell. Physiol. 215:538-49, 2008.
Raufman, J-P., Samimi, R., Shah, N., Khurana, S., Shant, J., Drachenberg, C., Xie, G., Wess, J., Cheng, K. Genetic ablation of M3 muscarinic receptors attenuates murine colon epithelial cell proliferation and neoplasia. Cancer Research (Priority Report) 68:3573-78, 2008.
Cheng, K., Samimi, R., Xie, G., Shant, J., Drachenberg, C., Wade, M., Davis, R.J., Nomikos, G., Raufman, J-P. Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation. Am. J. Physiol. (Gastrointest. Liver Physiol.) 295:G591-G597, 2008.
Shant, J., Cheng, K., Marasa, B., Wang, J-Y., Raufman, J-P. Akt-dependent NF-kappaB activation is required for bile acids to rescue colon cancer cells from stress-induced apoptosis. Exp. Cell Res. 315: 432-450, 2009.
Shah, N., Khurana, S., Cheng, K., Raufman, J-P. Muscarinic receptors and ligands in cancer. Am. J. Physiol. (Cell Physiol.) 296:C221-C232, 2009.
Xie, G., Cheng, K., Shant, J., Raufman, J-P. Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells. Am. J. Physiol. (Gastrointest. Liver Physiol.) 296:G755-G763, 2009.
Zheng, X., Ekins, S., Raufman, J-P., Polli, J. Computational models for drug inhibition of the human apical sodium-dependent bile acid transporter. Mol. Pharmaceutics 6:1591-1603, 2009.
Khurana S, Shah N, Cheng K, Shiu B, Samimi R, Belo A, Shant J, Drachenberg C, Wess J, Raufman J-P. Scopolamine treatment and muscarinic receptor subtype-3 gene ablation augment azoxymethane-induced murine liver injury. J Pharmacol Exp Ther. 333:639-49, 2010.