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Jean-Pierre Raufman, MD

Moses Paulson, MD and Helen Golden Paulson Chair in the Division of Gastroenterology

Academic Title:

Professor

Primary Appointment:

Medicine

Administrative Title:

Division Head, Gastroenterology & Hepatology

Location:

22 S. Greene Street, Room N3W62

Phone (Primary):

410-328-8728

Fax:

410-328-8315

Education and Training

Dr. Raufman is board certified in Internal Medicine and Gastroenterology. A graduate of Albert Einstein College of Medicine, with postdoctoral training at the University of Michigan and the National Institutes of Health, Dr. Raufman has published more than 175 original research papers and more than 30 book chapters. He is an elected member of the American Society for Clinical Investigation, has chaired several NIH Study Sections and FDA Advisory Panels, and serves on the Editorial Board of the Jounal of Clinical Investigation. Since 2005, Dr. Raufman is PI on a unique University of Maryland/NIH GI and Liver Scholars Fellowship Trainiing Program and Program Director for an NIDDK T32 Training Grant, Training in Gastroenterology and Hepatology 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 therapeutic targets.

Biosketch

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 200 peer-reviewed research papers, reviews and book chapters (including 19 first- or senior-author scientific publications in the American Journal of Physiology, 10 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).

Highlighted Publications

  • 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. 

  • 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 15:4827-34, 2018. 

  • Peng Z, Chen J, Drachenberg CB, Raufman J-P, Xie G. Farnesoid X receptor represses matrix metalloproteinase 7 expression, revealing this regulatory axis as a promising therapeutic target in colon cancer. J. Biol. Chem. 294:8529-8542, 2019.

  • Yu T, Chung HK, Xiao L, Piao J, Lan S, Rao JN, Turner DJ, Raufman J-P, Gorospe M, Wang J-Y. Long noncoding RNA H19 impairs the intestinal barrier by suppressing autophagy and lowering Paneth and goblet cell function. Cellular and Molecular Gastroenterology and Hepatology. 9:611-25; 2020. 

  • Garzel B, Hu T, Li L, Lu Y, Heyward S, Polli J, Zhang L, Huang S, Raufman J-P, Wang H. Metformin disrupts bile acid efflux by repressing bile salt export pump expression. Pharmaceutical Research 37:26; 2020. https://doi.org/10.1007/s11095-019-2753-x.

Research Interests

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 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. (b) Exploring the role of muscarinic receptor expression in colon cancer initiation and growth by studying colon cancer stem cells, organoids derived from normal and neoplastic small intestine and colon, and unique mouse models. Our long-term goal is to apply resulting advances in knowledge to prevent and treat colon cancer, the second most common cause of cancer death in the United States. 

Grants and Contracts

VA Merit Award BX002129             PI: Raufman, J-P                               01/01/15-03/30/21

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.

Role: PI

 

T32 DK067872               PI: J-P Raufman                                                  07/01/05-6/30/25

NIH/NIDDK                     Research Training in Gastroenterology and Hepatology

Role: PD; Director, Cell Signaling and Proliferation track

 

NIH Contract NO2-DK-5-2802                      Raufman (PI)                       07/01/05-06/30/21

NIH/NIDDK                      Gastroenterology Fellowship and Consultations at NIH

Role: PI

 

R01 DK068491              Wang, J-Y (PI)                                                    10/01/15-10/30/20

NIDDK                           Surgical studies of gut permeability

Role: Co-Investigator