Vanderbilt University School of Medicine

Coffey, Robert J. , M.D.
Professor of Medicine
Professor of Cell and Developmental Biology
Ingram Professor of Cancer Research

Lab Url:

Phone Number: 615-343-6228


Coffey, Robert's picture

Office Address   Mailing Address

Epithelial Biology Center, 10415-F MRB IV

10415-E MRB IV -0441 37232

Research Keywords
TGF-alpha, EGFR, Naked2, Epithelial Polarity, Vesicle Trafficking, GI Cancer, Menetrier's disease,Cancer,Developmental biology,Malignancy,Membrane,Molecular medicine,Mouse,Pathology,Post-transcriptional modification,Proteomics,Receptor,Stem cells,Transformation,Tyrosine phosphorylation

Research Description
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.

Cha, DJ, Franklin, JL, Dou, Y, Liu, Q, Higginbotham, JN, Demory Beckler, M, Weaver, AM, Vickers, K, Prasad, N, Levy, S, Zhang, B, Coffey, RJ, Patton, JG. KRAS-dependent sorting of miRNA to exosomes. Elife, 4, e07197, 2015.

French, CL, Ye, F, Revetta, F, Zhang, B, Coffey, RJ, Washington, MK, Deane, NG, Beauchamp, RD, Weaver, AM. Linking patient outcome to high throughput protein expression data identifies novel regulators of colorectal adenocarcinoma aggressiveness. F1000Res, 4, 99, 2015.

Gonzalez, RS, Cates, JM, Washington, MK, Beauchamp, RD, Coffey, RJ, Shi, C. Adenoma-like adenocarcinoma: a subtype of colorectal carcinoma with good prognosis, deceptive appearance on??biopsy and frequent KRAS mutation. Histopathology, , , 2015.

Kondo, J, Powell, AE, Wang, Y, Musser, MA, Southard-Smith, EM, Franklin, JL, Coffey, RJ. LRIG1 Regulates Ontogeny of Smooth Muscle-Derived Subsets of Interstitial Cells of Cajal in Mice. Gastroenterology, 149(2), 407-19.e8, 2015.

McKinley, ET, Watchmaker, JM, Chakravarthy, AB, Meyerhardt, JA, Engelman, JA, Walker, RC, Washington, MK, Coffey, RJ, Manning, HC. [(18)F]-FLT PET to predict early response to neoadjuvant therapy in KRAS wild-type rectal cancer: a pilot study. Ann Nucl Med, 29(6), 535-42, 2015.

Patton, JG, Franklin, JL, Weaver, AM, Vickers, K, Zhang, B, Coffey, RJ, Ansel, KM, Blelloch, R, Goga, A, Huang, B, L''Etoille, N, Raffai, RL, Lai, CP, Krichevsky, AM, Mateescu, B, Greiner, VJ, Hunter, C, Voinnet, O, McManus, MT. Biogenesis, delivery, and function of extracellular RNA. J Extracell Vesicles, 4, 27494, 2015.

Quesenberry, PJ, Aliotta, J, Camussi, G, Abdel-Mageed, AB, Wen, S, Goldberg, L, Zhang, HG, Tetta, C, Franklin, J, Coffey, RJ, Danielson, K, Subramanya, V, Ghiran, I, Das, S, Chen, CC, Pusic, KM, Pusic, AD, Chatterjee, D, Kraig, RP, Balaj, L, Dooner, M. Potential functional applications of extracellular vesicles: a report by the NIH Common Fund Extracellular RNA Communication Consortium. J Extracell Vesicles, 4, 27575, 2015.

Simmons, AJ, Banerjee, A, McKinley, ET, Scurrah, CR, Herring, CA, Gewin, LS, Masuzaki, R, Karp, SJ, Franklin, JL, Gerdes, MJ, Irish, JM, Coffey, RJ, Lau, KS. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-??-induced apoptosis in??vivo. Mol Syst Biol, 11(10), 835, 2015.

Singh, B, Bogatcheva, G, Starchenko, A, Sinnaeve, J, Lapierre, LA, Williams, JA, Goldenring, JR, Coffey, RJ. Induction of lateral lumens through disruption of a monoleucine-based basolateral-sorting motif in betacellulin. J Cell Sci, 128(18), 3444-55, 2015.

Wang, Y, Shi, C, Lu, Y, Poulin, EJ, Franklin, JL, Coffey, RJ. Loss of Lrig1 leads to expansion of brunner glands followed by duodenal adenomas with gastric metaplasia. Am J Pathol, 185(4), 1123-34, 2015.

Kawasaki, K, Freimuth, J, Meyer, DS, Lee, MM, Tochimoto-Okamoto, A, Benzinou, M, Clermont, FF, Wu, G, Roy, R, Letteboer, TG, Ploos van Amstel, JK, Giraud, S, Dupuis-Girod, S, Lesca, G, Westermann, CJ, Coffey, RJ, Akhurst, RJ. Genetic variants of Adam17 differentially regulate TGF?? signaling to modify vascular pathology in mice and humans. Proc Natl Acad Sci U S A, 111(21), 7723-8, 2014.

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.

Markham, NO, Doll, CA, Dohn, MR, Miller, RK, Yu, H, Coffey, RJ, McCrea, PD, Gamse, JT, Reynolds, AB. DIPA-family coiled-coils bind conserved isoform-specific head domain of p120-catenin family: potential roles in hydrocephalus and heterotopia. Mol Biol Cell, 25(17), 2592-603, 2014.

McKinley, ET, Zhao, P, Coffey, RJ, Washington, MK, Manning, HC. 3''-Deoxy-3''-[18F]-Fluorothymidine PET imaging reflects PI3K-mTOR-mediated pro-survival response to targeted therapy in colorectal cancer. PLoS One, 9(9), e108193, 2014.

Poulin, EJ, Powell, AE, Wang, Y, Li, Y, Franklin, JL, Coffey, RJ. Using a new Lrig1 reporter mouse to assess differences between two Lrig1 antibodies in the intestine. Stem Cell Res, 13(3 Pt A), 422-30, 2014.

Powell, AE, Vlacich, G, Zhao, ZY, McKinley, ET, Washington, MK, Manning, HC, Coffey, RJ. Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis. Am J Physiol Gastrointest Liver Physiol, 307(1), G16-23, 2014.

Zhang, B, Wang, J, Wang, X, Zhu, J, Liu, Q, Shi, Z, Chambers, MC, Zimmerman, LJ, Shaddox, KF, Kim, S, Davies, SR, Wang, S, Wang, P, Kinsinger, CR, Rivers, RC, Rodriguez, H, Townsend, RR, Ellis, MJ, Carr, SA, Tabb, DL, Coffey, RJ, Slebos, RJ, Liebler, DC, , . Proteogenomic characterization of human colon and rectal cancer. Nature, 513(7518), 382-7, 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. PMCID:3096651

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. PMCID:2859517

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.

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. PMCID:2528074

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. PMCID:2657180

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. PMCID:397424

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. PMCID:122223

Burdick, JS, Chung, E, Tanner, G, Sun, M, Paciga, JE, Cheng, JQ, Washington, K, Goldenring, JR, Coffey, RJ. Treatment of M??n??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.

Postdoctoral Position Available

Postdoctoral Position Details
Postdoctoral Fellowship Positions are immediately available within the Vanderbilt University Epithelial Biology Center. The Center is dedicated to the multi-disciplinary study of intra- and extra-cellular trafficking and signaling, establishment and maintenance of epithelial polarity, and role of intestinal stem cells in health and disease. Positions are immediately available in NIH-funded research programs to

characterize gastrointestinal stem cells and their role in mouse and human neoplasia. Mouse work will be facilitated using newly developed compartment-selective Cre drivers;

advance the recent discovery that EGF receptor ligands signal via exosomes and that mutant KRAS affects the protein and RNA composition and behavior of exosomes.

Individuals with prior experience in exosomal trafficking and function, mouse modeling, trafficking in polarized epithelial cells, and/or high resolution microscopy are especially encouraged to apply.

Salaries commensurate with previous training. Send CVs to Robert J. Coffey, MD, at

Updated Date

Vanderbilt University is committed to principles of equal opportunity and affirmative action.
Copyright 2008 Vanderbilt University School of Medicine
The office of Biomedical Research Education & Training All rights reserved.
For questions or problems concerning this page, please submit a help ticket.