Robert J. Coffey, M.D.
Ingram Professor of Cancer Research
Professor of Medicine (Gastroenterology, Hepatology and Nutrition)
Professor of Cell and Developmental Biology
2213 Garland Avenue
10415 MRB IV -0441
Nashville, TN 37232
The focus of research within the Coffey lab is the study of the role of the EGF receptor (EGFR) and its ligands in GI neoplasia. The lab has a particular interest in the trafficking of EGFR ligands in polarizing colonic epithelial cells. Naked2 has been identified as a critical regulator of basolateral trafficking of TGF-alpha, a major EGFR ligand. Naked2 is a known antagonist of Wnt-beta-catenin signaling so Naked2 provides a point of convergence between EGFR and Wnt signaling. This work has led to the identification of a new mode of EGFR ligand signaling via exosomes and the development of FAVS (fluorescent-activated vesicle sorting) to isolate and characterize cellular organelles. The lab has recently found that Lrig1, an inducible negative regulator of the EGFR, marks proliferative and quiescent intestinal stem cells, and acts as a tumor suppressor.
- Li, C, Ma, H, Wang, Y, Cao, Z, Graves-Deal, R, Powell, AE, Starchenko, A, Ayers, GD, Washington, MK, Kamath, V, Desai, K, Gerdes, MJ, Solnica-Krezel, L, Coffey, RJ Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer. J Clin Invest, 2014.
- Tanksley, JP, Chen, X, Coffey, RJ NEDD4L is downregulated in colorectal cancer and inhibits canonical WNT signaling. PLoS One, 8(11), e81514, 2013.
- Powell, AE, Wang, Y, Li, Y, Poulin, EJ, Means, AL, Washington, MK, Higginbotham, JN, Juchheim, A, Prasad, N, Levy, SE, Guo, Y, Shyr, Y, Aronow, BJ, Haigis, KM, Franklin, JL, Coffey, RJ The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell, 149(1), 146-58, 2012.
- Higginbotham, JN, Demory Beckler, M, Gephart, JD, Franklin, JL, Bogatcheva, G, Kremers, GJ, Piston, DW, Ayers, GD, McConnell, RE, Tyska, MJ, Coffey, RJ Amphiregulin exosomes increase cancer cell invasion. Curr Biol, 21(9), 779-86, 2011.
- Hu, T, Li, C, Cao, Z, Van Raay, TJ, Smith, JG, Willert, K, Solnica-Krezel, L, Coffey, RJ Myristoylated Naked2 antagonizes Wnt-beta-catenin activity by degrading Dishevelled-1 at the plasma membrane. J Biol Chem, 285(18), 13561-8, 2010.
- Fiske WH, Tanksley J, Nam KT, Goldenring JR, Slebos RJC, Liebler DC, Abtahi AM, La Fleur B, Ayers JD, Lind CD, Washington MK and Coffey RJ Efficacy of cetuximab in the treatment of Menetrier's disease. Science Translational Medicine , 2009.
- Ding W, Li C, Hu T, Graves-Deal R, Fotia AB, Weissman AM and Coffey RJ EGF receptor-independent action of TGF-alpha protects Naked2 from AO7-mediated ubiquitylation and proteasomal degradation. Proc Natl Acad Sci U S A , (105), 13433-134338, 2008.
- Manning, HC, Merchant, NB, Foutch, AC, Virostko, JM, Wyatt, SK, Shah, C, McKinley, ET, Xie, J, Mutic, NJ, Washington, MK, Lafleur, B, Tantawy, MN, Peterson, TE, Ansari, MS, Baldwin, RM, Rothenberg, ML, Bornhop, DJ, Gore, JC, Coffey, RJ Molecular Imaging of Therapeutic Response to Epidermal Growth Factor Receptor Blockade in Colorectal Cancer. Clin Cancer Res, 14(22), 7413-7422, 2008.
- Cao, Z, Li, C, Higginbotham, JN, Franklin, JL, Tabb, DL, Graves-Deal, R, Hill, S, Cheek, K, Jerome, WG, Lapierre, LA, Goldenring, JR, Ham, AJ, Coffey, RJ Use of fluorescence-activated vesicle sorting for isolation of Naked2-associated, basolaterally-targeted exocytic vesicles for proteomic analysis. Mol Cell Proteomics, 7(9), 1651-67, 2008.
- Rothenberg, ML, LaFleur, B, Levy, DE, Washington, MK, Morgan-Meadows, SL, Ramanathan, RK, Berlin, JD, Benson, AB, Coffey, RJ Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma. J Clin Oncol, 23(36), 9265-74, 2005.
- Li, C, Franklin, JL, Graves-Deal, R, Jerome, WG, Cao, Z, Coffey, RJ Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells. Proc Natl Acad Sci U S A, 101(15), 5571-6, 2004.
- Roberts, RB, Min, L, Washington, MK, Olsen, SJ, Settle, SH, Coffey, RJ, Threadgill, DW Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. Proc Natl Acad Sci U S A, 99(3), 1521-6, 2002.
- Burdick, JS, Chung, E, Tanner, G, Sun, M, Paciga, JE, Cheng, JQ, Washington, K, Goldenring, JR, Coffey, RJ Treatment of MÃ©nÃ©trier''s disease with a monoclonal antibody against the epidermal growth factor receptor. N Engl J Med, 343(23), 1697-701, 2000.
- Dempsey, PJ, Coffey, RJ Basolateral targeting and efficient consumption of transforming growth factor-alpha when expressed in Madin-Darby canine kidney cells. J Biol Chem, 269(24), 16878-89, 1994.
- Matsui, Y, Halter, SA, Holt, JT, Hogan, BL, Coffey, RJ Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice. Cell, 61(6), 1147-55, 1990.
- Coffey, RJ, Derynck, R, Wilcox, JN, Bringman, TS, Goustin, AS, Moses, HL, Pittelkow, MR Production and auto-induction of transforming growth factor-alpha in human keratinocytes. Nature, 328(6133), 817-20, 1987.