|Administrative Title: Division Head
Moses and Helen Golden Paulson Professor of Medicine
22 S. Greene Street,
Dr. 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 150 original papers and more than 25 book chapters. He is a member of the American Society for Clinical Investigation and has served 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, PKC, p38 MAPK, and NF-κB. Moreover, the role of matrix metalloproteases (MMP1, MMP7, and MMP10) in regulating downstream effects of muscarinic receptor signaling is actively investigated by the Raufman lab. For example, work now focuses on functional interaction between M3 muscarinic receptors and MMP1, a collagenase whose expression in colon cancer cells is robustly increased by M3R activation. We are exploring the mechanisms whereby M3R agonists promote MMP1 gene induction by newly-identified cross-talk between EGFR/ERK and PKC/p38, and will test the hypothesis that MMP1 can be targeted successfully to attenuate colon cancer cell invasion and dissemination. The long-term goal is to apply resulting advances in knowledge to prevent and treat colon cancer metastasis.
- Belo A, Cheng K, Chahdi A, Shant J, Xie G, Khurana S, Raufman J-P. Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion. Am. J. Physiol. (Gastrointest. Liver Physiol.) 300:G749-G760, 2011 (PMCID 3094147).
- Raufman J-P, Xu S, Cheng K, Khurana S, Johnson D, Shao C, Kane M, Shi D, Gullapalli R, Polli JE. In vivo magnetic resonance imaging to detect biliary excretion of 19F-labeled drug in mice. Drug Metab. Dispos. 39:736-739, 2011.
- Raufman J-P, Shant J, Xie G, Cheng K, Gao X, Shiu B, Shah N, Drachenberg C, Heath J, Wess J, Khurana S. Muscarinic receptor subtype-3 gene ablation and scopolamine butylbromide treatment attenuate small intestinal neoplasia in Apcmin/+ mice. Carcinogenesis 32:1396-1402, 2011 (PMCID 3165126).
- Raufman J-P, Cheng K, Saxena N, Chahdi A, Belo A, Khurana, S, Xie, G. Muscarinic receptor agonists stimulate matrix metalloproteinase1-dependent invasion of human colon cancer cells. Biochem Biophys Res Comm. 415:319-324, 2011 (PMCID 3221914).
- Xie G, Peng Z, Raufman J-P. Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross-talk stimulates colon cancer cell proliferation. Am. J. Physiol. (Gastrointest. Liver Physiol.) 302:G1006-G1015, 2012 (PMCID 3362076).
- Peng Z, Raufman J-P, Xie G. Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis. PLoS ONE 7:e48461, 2012 (PMCID 3485230).
- Vivian D, Cheng K, Khurana S, Xu S, Whiterock V, Witter D, Lentz K, Santone K, Raufman J-P*, Polli JE*. Design and characterization of a novel fluorinated magnetic resonance Imaging agent for functional analysis of bile acid transporter activity. Pharmaceutical Res. 30:1240-51, 2013 (DOI 10.1007/s11095-012-0963-6). PMCID:PMC3618595 *co-corresponding/senior authors.
- Peng Z, Heath J, Drachenberg C, Raufman J-P, Xie G. Cholinergic muscarinic receptor activation augments murine intestinal epithelial cell proliferation and tumorigenesis. BMC Cancer 13:204, 2013 (http://www.biomedcentral.com/1471-2407/13/204)
- Khurana S, Jadeja R, Twadell W, Cheng K, Rachakonda V, Saxena N, Raufman J-P. Effects of modulating M3 muscarinic receptor activity on azoxymethane-induced liver injury in mice. Biochem. Pharmacol. 86:329-338, 2013. PMCID:PMC3699334
- von Rosenvinge E, Cheng K, Drachenberg C, Fowler CB, Evers DL, Xie G, Raufman J-P. Role of muscarinic receptor activation in ultrarapid growth of colorectal cancer in a patient with pheochromocytoma. Mayo Clin. Proc. 88:1340-6, 2013.
- Chahdi A, Raufman J-P. The Cdc42/Rac nucleotide exchange factor β1Pix modulates β-catenin transcriptional activity in colon cancer cells. J. Biol. Chem. 288:34019-34029, 2013.
- Vivian D, Cheng K, Khurana S, Xu S, Kriel E, Dawson P, Raufman J-P*, Polli J*. In vivo performance of a novel fluorinated magnetic resonance imaging agent for functional analysis of bile acid transport. Mol. Pharmaceutics. 11:1575-82, 2014. *co-corresponding/senior authors.
- Cheng K, Xie G, Khurana S, Heath J, Drachenberg C, Timmons J, Shan N, Raufman J-P. Divergent effects of muscarinic receptor subtype gene ablation on murine colon tumorigenesis reveals association of M3R and zinc finger protein 277 expression in colon neoplasia. Mol. Cancer. 13:77, 2014. doi:10.1186/1476-4598-13-77
- Vivian D, Cheng K, Khurana S, Xu S, Dawson P, Raufman J-P*, Polli J*. Design and evaluation of a novel tri-fluorinated imaging agent for assessment of bile acid transport using fluorine magnetic resonance imaging (MRI). J. Pharm. Sci. 2014 (in press). *co-corresponding/senior authors. DOI 10.1002/jps.24131
- Said, A., Raufman JP and Xie, G. The role of matrix metalloproteinases in colorectal cancer. Cancers. 6(1):366-75, 2014. (Special Issue: Matrix Metalloproteinases in Cancer Progress). (Review)
- Urrunaga NH, Jadeja RN, Rachakonda V, Ahmad D, McLean LP, Cheng K, Shah V, Twaddell WS, Raufman J-P, Khurana S. M1 muscarinic receptors modify oxidative stress response to acetaminophen-induced acute liver injury. Free Radical Biology & Medicine 2014 (in press).