Division Head, Gastroenterology & Hepatology
22 S. Greene Street, Room N3W62
Education and Training
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 is a member of the Molecular and Structural Biology Program within the University of Maryland Marlene and Stewart Greenebaum Cancer Center Program in Oncology. As such, he collaborates with both basic and clinical research investigators to identify candidate proteins and genes that are relevant to muscarinic receptor signaling in colon cancer and may serve as markers for malignancy and/or targets for new drugs.
I completed GI Fellowship training at the University of Michigan where I worked in the lab of Dr. Jorge Gumucio (1978-80). I obtained three more years of research training at the National Institutes of Health in the NIDDK, Digestive Diseases Branch under the mentorship of Drs. Jerry D. Gardner and Robert T. Jensen (1980-83). Since July 1983, I maintain an independent research program whose unifying theme is the study of gastrointestinal regulatory molecules and signal transduction; I have been funded by R01, R21 and T32 awards from NIH (NIDDK and NCI), by the VA Merit program, and by foundations (e.g. AGA/Industry Award). I presented my work at prominent national meetings, secured patents, and published more than 180 peer-reviewed research papers, reviews and book chapters (including 19 first- or senior-author scientific publications in the American Journal of Physiology, nine in the Journal of Biological Chemistry, three each in Biochemical Pharmacology and Biomedical Biophysical Research Communications, two each in Cancer Research, Journal of Pharmacology and Experimental Therapeutics, Carcinogenesis, Molecular Cancer, and PLoS One, and one each in Proceedings of the National Academy of Sciences (USA), Experimental Cell Research, and the Biochemical Journal).
Raufman J-P, Dawson PA, Rao A, Drachenberg CB, Heath J, Shang AC, Hu S, Zhan M, Polli JE, Cheng K. Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids. Carcinogenesis 36:1193-1200, 2015.
Rachakonda V, Jadeja R, Urrunaga N, Shah N, Ahmad D, Cheng K, Twaddell W, Raufman, J-P, Khurana S. M1 muscarinic receptor deficiency attenuates azoxymethane-induced chronic liver injury in mice. Scientific Reports 5:14110, 2015.
Hu S, Liu L, Chang EB, Wang J-Y, Raufman J-P. Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells. Molecular Cancer 14:180, 2015.
McLean L, Smith A, Cheung L, Urban J, Sun R, Grinchuk V, Desai N, Zhao A, Raufman J-P, Shea-Donohue T. Type 3 muscarinic receptors contribute to intestinal mucosal homeostasis and clearance of Nippostrongylus brasiliensis through Induction of Th2 cytokines. Amer. J. Physiol. (Gastrointest. Liver Physiol.) 311:G130-141, 2016.
Felton J, Cheng K, Said A, Shang AC, Xu S, Vivian D, Metry M, Polli J, Raufman J-P. Using multi-fluorinated bile acids and in vivo magnetic resonance imaging to measure bile acid transport. Journal of Visualized Experiments (JoVE) Date Published: 11/27/2016, doi: 10.3791/54597.
Cheng K, Shang AC, Drachenberg CB, Zhan M, Raufman J-P. Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis. Oncotarget 8:21106-14, 2017.
Said A, Hu A, Abutaleb A, Watkins T, Cheng K, Chahdi A, Kuppusamy P, Saxena N, Xie G, Raufman J-P. Interacting post-muscarinic receptor signaling pathways potentiate matrix metalloproteinase-1 expression and invasion of human colon cancer cells. Biochem J. 474:647-665, 2017.
Durchschein F, Krones E, Pollheimer M, Zollner G, Wagner M, Raufman J-P, Fickert P. Genetic loss of the muscarinic M3 receptor (M3-R) markedly alters bile formation and cholestatic liver injury in mice. Hepatology Res. 48(3):E68-E77, 2018.
Mindikoglu AL, Opekun AR, Mitch WE, Magder LS, Christenson RH, Dowling TC, Weir MR, Seliger SL, Howell CD, Raufman J-P, Rana A, Goss JA, Khaderi SA, Vierling JM. Cystatin C is a gender-neutral glomerular filtration rate biomarker in patients with cirrhosis. Dig. Dis. Sci. 63:665-675, 2018
Mindikoglu AL, Opekun AR, Putluri N, Devaraj S, Sheikh-Hamad D, Vierling JM, Goss JA, Rana A, Sood GK, Jalal PK, Inker LA, Mohney RP, Tighiouart H, Christenson RH, Dowling TC, Weir MR, Seliger SL, Hutson WR, Howell CD, Raufman J-P, Magder LS, Coarfa C. Unique metabolomic signature associated with hepatorenal dysfunction and mortality in cirrhosis. Transl. Res. 195:25-47, 2018
Wong U, Person, EB, Castell DO, von Rosenvinge E, Raufman, J-P, Xie G. Improving high-resolution impedance manometry: A prospective study establishing normative values for novel viscous and super-viscous substrates. J. Neurogastroenterol. Motil. 24(4):570-576, 2018.
Cheng K, Metry M, Felton J, Shang AC, Drachenberg CB, Su X, Zhan M, Schumacher J, Guo G, Polli JE, Raufman, J-P. Diminished gallbladder filling, increased fecal bile acids, and promotion of colon epithelial cell proliferation and neoplasia in fibroblast growth factor 15-deficient mice. Oncotarget 9:25572-25585, 2018.
Felton J, Cheng K, Shang AC, Hu S, Larabee S, Drachenberg CB, Raufman J-P. Two sides to colon cancer: Mice mimic human anatomical region disparity in colon cancer development and progression. J. Cancer Metastasis Treat. 4:51, 2018.
Metry M, Felton J, Cheng K, Xu S, Ai Y, Xue F, Raufman J-P, Polli, J. Attenuated accumulation of novel fluorine (19F)-labeled bile acid analogues in gallbladders of fibroblast growth factor-15 (FGF15)-deficient mice. Mol. Pharmaceutics 2018 (In press). doi: 10.1021/acs.molpharmaceut.8b00454
Over the past decade, our laboratory has explored the implications of my discovery that bile acids interact functionally with muscarinic receptors. Whereas it was observed for decades that changes in fecal bile acid composition increase the risk of colon cancer in both animal models and humans, the underlying mechanisms were elusive. Colon cancer cells over-express muscarinic receptor subtype 3 (M3R; gene name CHRM3). We found that bile acids and conventional muscarinic agonists (e.g. acetylcholine) stimulate colon cancer cell proliferation and survival by activating M3R, trans-activating EGFR and stimulating post-receptor signaling, primarily via ERK and PI3K activation. In vivo work using two mouse models of colon cancer revealed that activation of muscarinic receptors increases the number of colon adenocarcinomas, whereas reduced expression or activation of M3R attenuates colon neoplasia.
The work in our lab currently focuses on: (a) Elucidating the functional interaction between M3R and MMP1, a collagenase whose expression in colon cancer cells is robustly increased by M3R activation. With VA Merit funding, 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. (b) Elucidating the role of a Cdc42/Rac nucleotide exchange factor, βPix, as a pivotal molecule mediating interaction between muscarinic receptor and β-catenin signaling in colon cancer. To accomplish this goal we created mice with conditional intestine-selective βPix deletion.
Our long-term goal is to apply resulting advances in knowledge to prevent and treat colon cancer. Publications of particular importance with regard to our work in colon cancer include:
Cheng, K, Zimniak, P, Raufman, J-P. Transactivation of the epidermal growth factor receptor mediates cholinergic agonist-induced proliferation of H508 colon cancer cells. Cancer Res. 63:6744-50, 2003.
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 Res. (Priority Report) 68:3573-78, 2008. (PMCID 2577901)
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. (PMCID 3837141)
Hu S, Liu L, Chang EB, Wang J-Y, Raufman J-P. Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells. Molecular Cancer 14:180, 2015. doi: 10.1186/s12943-015-0450-x
VA Merit Award BX002129 PI: Raufman, J-P 10/01/14-09/30/19
Department of Veterans Affairs M3R, MMP1 and Colon Cancer Dissemination
The goals are to determine the mechanisms whereby M3R agonist-induced MMP1 expression stimulates human colon cancer cell invasion and dissemination.
PI: J-PRaufman 07/01/05-6/30/20
NIH/NIDDK Research Training in Gastroenterology
Role: PD; Director, Cell Signaling and Proliferation track
NIH Contract NO2-DK-5-2802 Raufman (PI) 07/01/05-06/30/20
NIH/NIDDK Gastroenterology Fellowship and Consultations at NIH
VA Merit Award Wang, J-Y (PI) 04/01/14-03/31/18
Department of Veterans Affairs Regulation of intestinal epithelial restituition
The goals are to determine the roles and mechanisms of RNA-binding protein HuR and microRNAs in the regulation of GI mucosal restitution after mucosal injury.
R01 DK068491 Wang, J-Y (PI) 10/01/15-10/30/20
NIDDK Surgical studies of gut permeability
T32 DK098107 Taylor, S (PI) 07/01/15-06/30/18
NIDDK Diabetes and its metabolic complications
Role: Internal Advisory Committee