Robert J. Coffey, Jr. M.D.

Ingram Professor of Cancer Research

Professor of Medicine


Division

Gastroenterology, Hepatology and Nutrition

Education:

M.D. - Medicine, Georgetown University, Washington, District of Columbia

A.B. - Political Science, Princeton University, Princeton, New Jersey


Office Address:
104 15-E MRBIV (0441), Nashville, TN 37232-0441

Robert J. Coffey, Jr. M.D.


Research Focus:

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.

Phone No. 

615-343-1590

Research Keywords 

TGF-alpha, EGFR, Naked2, Epithelial Polarity, Vesicle Trafficking, GI Cancer, Menetrier's disease

publications 

​Wang J, Mouradov D, Wang X, Jorissen RN, Chambers MC, Zimmerman LJ, Vasaikar S, Love CG, Li S, Lowes K, Leuchowius KJ, Jousset H, Weinstock J, Yau C, Mariadason J, Shi Z, Ban Y, Chen X, Coffey RJC, Slebos RJC, Burgess AW, Liebler DC, Zhang B, Sieber OM. Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug SensitivityGastroenterology [print-electronic]. 2017 Oct; 153(4): 1082-95. PMID: 28625833, PMCID: PMC5623120, PII: S0016-5085(17)35742-6, DOI: 10.1053/j.gastro.2017.06.008, ISSN: 1528-0012. 

Choi E, Lantz TL, Vlacich G, Keeley TM, Samuelson LC, Coffey RJ, Goldenring JR, Powell AE. Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomachGut [print-electronic]. 2017 Aug 8/16/2017; PMID: 28814482, PII: gutjnl-2017-313874, DOI: 10.1136/gutjnl-2017-313874, ISSN: 1468-3288. 

Choi E, Lantz TL, Vlacich G, Keeley TM, Samuelson LC, Coffey RJ, Goldenring JR, Powell AE. Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomachGut [print-electronic]. 2017 Aug 8/16/2017; PMID: 28814482, PII: gutjnl-2017-313874, DOI: 10.1136/gutjnl-2017-313874, ISSN: 1468-3288. 

Shah AT, Cannon TM, Higginbotham JN, Coffey RJ, Skala MC. Autofluorescence flow sorting of breast cancer cell metabolismJ Biophotonics [print-electronic]. 2017 Aug; 10(8): 1026-33. PMID: 27730745, PMCID: PMC5547001, DOI: 10.1002/jbio.201600128, ISSN: 1864-0648. 

Wang J, Mouradov D, Wang X, Jorissen RN, Chambers MC, Zimmerman LJ, Vasaikar S, Love CG, Li S, Lowes K, Leuchowius KJ, Jousset H, Weinstock J, Yau C, Mariadason J, Shi Z, Ban Y, Chen X, Coffey RJC, Slebos RJC, Burgess AW, Liebler DC, Zhang B, Sieber OM. Colorectal cancer cell line proteomes are representative of primary tumors and predict drug sensitivityGastroenterology [print-electronic]. 2017 Jun 6/15/2017; PMID: 28625833, PII: S0016-5085(17)35742-6, DOI: 10.1053/j.gastro.2017.06.008, ISSN: 1528-0012. 

McKinley ET, Sui Y, Al-Kofahi Y, Millis BA, Tyska MJ, Roland JT, Santamaria-Pang A, Ohland CL, Jobin C, Franklin JL, Lau KS, Gerdes MJ, Coffey RJOptimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneityJCI Insight [print-electronic]. 2017 Jun 6/2/2017; 2(11): PMID: 28570279, PMCID: PMC5453701, PII: 93487, DOI: 10.1172/jci.insight.93487, ISSN: 2379-3708. 

McKinley ET, Sui Y, Al-Kofahi Y, Millis BA, Tyska MJ, Roland JT, Santamaria-Pang A, Ohland CL, Jobin C, Franklin JL, Lau KS, Gerdes MJ, Coffey RJOptimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneityJCI Insight [print-electronic]. 2017 Jun 6/2/2017; 2(11): PMID: 28570279, PMCID: PMC5453701, PII: 93487, DOI: 10.1172/jci.insight.93487, ISSN: 2379-3708. 

Starchenko A, Graves-Deal R, Yang YP, Li C, Zent R, Singh B, Coffey RJClustering of integrin a5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cellsMol. Biol. Cell [print-electronic]. 2017 May 5/15/2017; 28(10): 1288-300. PMID: 28356422, PMCID: PMC5426844, PII: mbc.E16-12-0852, DOI: 10.1091/mbc.E16-12-0852, ISSN: 1939-4586. 

Yang YP, Ma H, Starchenko A, Huh WJ, Li W, Hickman FE, Zhang Q, Franklin JL, Mortlock DP, Fuhrmann S, Carter BD, Ihrie RA, Coffey RJA Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In VivoCell Rep. 2017 May 5/9/2017; 19(6): 1257-67. PMID: 28494873, PMCID: PMC5517093, PII: S2211-1247(17)30542-9, DOI: 10.1016/j.celrep.2017.04.048, ISSN: 2211-1247. 

Yang YP, Ma H, Starchenko A, Huh WJ, Li W, Hickman FE, Zhang Q, Franklin JL, Mortlock DP, Fuhrmann S, Carter BD, Ihrie RA, Coffey RJA Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In VivoCell Rep. 2017 May 5/9/2017; 19(6): 1257-67. PMID: 28494873, PMCID: PMC5517093, PII: S2211-1247(17)30542-9, DOI: 10.1016/j.celrep.2017.04.048, ISSN: 2211-1247. 

Li C, Singh B, Graves-Deal R, Ma H, Starchenko A, Fry WH, Lu Y, Wang Y, Bogatcheva G, Khan MP, Milne GL, Zhao S, Ayers GD, Li N, Hu H, Washington MK, Yeatman TJ, McDonald OG, Liu Q, Coffey RJThree-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancerProc. Natl. Acad. Sci. U.S.A [print-electronic]. 2017 Apr 4/4/2017; 114(14): E2852-E2861. PMID: 28320945, PII: 1618297114, DOI: 10.1073/pnas.1618297114, ISSN: 1091-6490. 

Li C, Singh B, Graves-Deal R, Ma H, Starchenko A, Fry WH, Lu Y, Wang Y, Bogatcheva G, Khan MP, Milne GL, Zhao S, Ayers GD, Li N, Hu H, Washington MK, Yeatman TJ, McDonald OG, Liu Q, Coffey RJThree-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancerProc. Natl. Acad. Sci. U.S.A [print-electronic]. 2017 Apr 4/4/2017; 114(14): E2852-E2861. PMID: 28320945, PMCID: PMC5389279, PII: 1618297114, DOI: 10.1073/pnas.1618297114, ISSN: 1091-6490. 

Starchenko A, Graves-Deal R, Yang YP, Li C, Zent R, Singh B, Coffey RJClustering of Integrin alpha 5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cellsMol. Biol. Cell [print-electronic]. 2017 Mar 3/29/2017; PMID: 28356422, PII: mbc.E16-12-0852, DOI: 10.1091/mbc.E16-12-0852, ISSN: 1939-4586. 

Gonzalez RS, Huh WJ, Cates JM, Washington K, Beauchamp RD, Coffey RJ, Shi C. Micropapillary colorectal carcinoma: clinical, pathological and molecular properties, including evidence of epithelial-mesenchymal transitionHistopathology [print-electronic]. 2017 Jan; 70(2): 223-31. PMID: 27560620, DOI: 10.1111/his.13068, ISSN: 1365-2559. 

Gonzalez RS, Huh WJ, Cates JM, Washington K, Beauchamp RD, Coffey RJ, Shi C. Micropapillary colorectal carcinoma: clinical, pathological and molecular properties, including evidence of epithelial-mesenchymal transitionHistopathology [print-electronic]. 2017 Jan; 70(2): 223-31. PMID: 27560620, DOI: 10.1111/his.13068, ISSN: 1365-2559. 

Dou Y, Cha DJ, Franklin JL, Higginbotham JN, Jeppesen DK, Weaver AM, Prasad N, Levy S, Coffey RJ, Patton JG, Zhang B. Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomesSci Rep. 2016 Nov 11/28/2016; 6: 37982. PMID: 27892494, PMCID: PMC5125100, PII: srep37982, DOI: 10.1038/srep37982, ISSN: 2045-2322. 

Dou Y, Cha DJ, Franklin JL, Higginbotham JN, Jeppesen DK, Weaver AM, Prasad N, Levy S, Coffey RJ, Patton JG, Zhang B. Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomesSci Rep. 2016 Nov 11/28/2016; 6: 37982. PMID: 27892494, PMCID: PMC5125100, PII: srep37982, DOI: 10.1038/srep37982, ISSN: 2045-2322. 

Shah AT, Cannon TM, Higginbotham JN, Coffey RJ, Skala MC. Autofluorescence flow sorting of breast cancer cell metabolismJ Biophotonics [print-electronic]. 2016 Oct 10/12/2016; PMID: 27730745, DOI: 10.1002/jbio.201600128, ISSN: 1864-0648. 

Simmons AJ, Scurrah CR, McKinley ET, Herring CA, Irish JM, Washington MK, Coffey RJ, Lau KS. Impaired coordination between signaling pathways is revealed in human colorectal cancer using single-cell mass cytometry of archival tissue blocksSci Signal. 2016 Oct 10/11/2016; 9(449): rs11. PMID: 27729552, PMCID: PMC5111815, PII: 9/449/rs11, DOI: 10.1126/scisignal.aah4413, ISSN: 1937-9145. 

Simmons AJ, Scurrah CR, McKinley ET, Herring CA, Irish JM, Washington MK, Coffey RJ, Lau KS. Impaired coordination between signaling pathways is revealed in human colorectal cancer using single-cell mass cytometry of archival tissue blocksSci Signal. 2016 Oct 10/11/2016; 9(449): rs11. PMID: 27729552, PMCID: PMC5111815, PII: 9/449/rs11, DOI: 10.1126/scisignal.aah4413, ISSN: 1937-9145. 

McKenzie AJ, Hoshino D, Hong NH, Cha DJ, Franklin JL, Coffey RJ, Patton JG, Weaver AM. KRAS-MEK Signaling Controls Ago2 Sorting into ExosomesCell Rep [print-electronic]. 2016 May 5/3/2016; 15(5): 978-87. PMID: 27117408, PMCID: PMC4857875, PII: S2211-1247(16)30387-4, DOI: 10.1016/j.celrep.2016.03.085, ISSN: 2211-1247. 

McKenzie AJ, Hoshino D, Hong NH, Cha DJ, Franklin JL, Coffey RJ, Patton JG, Weaver AM. KRAS-MEK Signaling Controls Ago2 Sorting into ExosomesCell Rep [print-electronic]. 2016 May 5/3/2016; 15(5): 978-87. PMID: 27117408, PMCID: PMC4857875, PII: S2211-1247(16)30387-4, DOI: 10.1016/j.celrep.2016.03.085, ISSN: 2211-1247. 

Singh B, Carpenter G, Coffey RJEGF receptor ligands: recent advancesF1000Res. 2016; 5: PMID: 27635238, PMCID: PMC5017282, DOI: 10.12688/f1000research.9025.1. 

Higginbotham JN, Zhang Q, Jeppesen DK, Scott AM, Manning HC, Ochieng J, Franklin JL, Coffey RJIdentification and characterization of EGF receptor in individual exosomes by fluorescence-activated vesicle sortingJ Extracell Vesicles. 2016; 5: 29254. PMID: 27345057, PMCID: PMC4921784, PII: 29254. 

Huh WJ, Coffey RJ, Washington MK. Ménétrier's Disease: Its Mimickers and PathogenesisJ Pathol Transl Med [print-electronic]. 2016 Jan; 50(1): 10-6. PMID: 26689786, PMCID: PMC4734964, PII: jptm.2015.09.15, DOI: 10.4132/jptm.2015.09.15, ISSN: 2383-7837. 

Yu HH, Dohn MR, Markham NO, Coffey RJ, Reynolds AB. P120-catenin controls contractility along the vertical axis of epithelial lateral membranesJ. Cell. Sci [print-electronic]. 2016 Jan 1/1/2016; 129(1): 80-94. PMID: 26585313, PMCID: PMC4732297, PII: jcs.177550, DOI: 10.1242/jcs.177550, ISSN: 1477-9137. 

Singh B, Carpenter G, Coffey RJEGF receptor ligands: recent advancesF1000Res. 2016; 5: PMID: 27635238, PMCID: PMC5017282, DOI: 10.12688/f1000research.9025.1, ISSN: 2046-1402. 

Higginbotham JN, Zhang Q, Jeppesen DK, Scott AM, Manning HC, Ochieng J, Franklin JL, Coffey RJIdentification and characterization of EGF receptor in individual exosomes by fluorescence-activated vesicle sortingJ Extracell Vesicles. 2016; 5: 29254. PMID: 27345057, PMCID: PMC4921784, PII: 29254, ISSN: 2001-3078. 

Huh WJ, Coffey RJ, Washington MK. Ménétrier's Disease: Its Mimickers and PathogenesisJ Pathol Transl Med [print-electronic]. 2016 Jan; 50(1): 10-6. PMID: 26689786, PMCID: PMC4734964, PII: jptm.2015.09.15, DOI: 10.4132/jptm.2015.09.15, ISSN: 2383-7837. 

Yu HH, Dohn MR, Markham NO, Coffey RJ, Reynolds AB. P120-catenin controls contractility along the vertical axis of epithelial lateral membranesJ. Cell. Sci [print-electronic]. 2016 Jan 1/1/2016; 129(1): 80-94. PMID: 26585313, PMCID: PMC4732297, PII: jcs.177550, DOI: 10.1242/jcs.177550, ISSN: 1477-9137. 

Singh B, Bogatcheva G, Starchenko A, Sinnaeve J, Lapierre LA, Williams JA, Goldenring JR, Coffey RJInduction of lateral lumens through disruption of a monoleucine-based basolateral-sorting motif in betacellulinJ. Cell. Sci [print-electronic]. 2015 Sep 9/15/2015; 128(18): 3444-55. PMID: 26272915, PMCID: PMC4582402, PII: jcs.170852, DOI: 10.1242/jcs.170852, ISSN: 1477-9137. 

Kondo J, Powell AE, Wang Y, Musser MA, Southard-Smith EM, Franklin JL, Coffey RJLRIG1 Regulates Ontogeny of Smooth Muscle-Derived Subsets of Interstitial Cells of Cajal in MiceGastroenterology [print-electronic]. 2015 Aug; 149(2): 407-19.e8. PMID: 25921371, PMCID: PMC4527342, PII: S0016-5085(15)00574-0, DOI: 10.1053/j.gastro.2015.04.018, ISSN: 1528-0012. 

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 studyAnn Nucl Med [print-electronic]. 2015 Jul; 29(6): 535-42. PMID: 25899481, PMCID: PMC4503488, DOI: 10.1007/s12149-015-0974-6, ISSN: 1864-6433. 

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 mutationHistopathology [print-electronic]. 2015 Apr 4/24/2015; PMID: 25913616, PMCID: PMC4619179, DOI: 10.1111/his.12725, ISSN: 1365-2559. 

Wang Y, Shi C, Lu Y, Poulin EJ, Franklin JL, Coffey RJLoss of Lrig1 leads to expansion of Brunner glands followed by duodenal adenomas with gastric metaplasiaAm. J. Pathol. 2015 Apr; 185(4): 1123-34. PMID: 25794708, PMCID: PMC4380843, PII: S0002-9440(15)00022-X, DOI: 10.1016/j.ajpath.2014.12.014, ISSN: 1525-2191. 

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-a-induced apoptosis in vivoMol. Syst. Biol. 2015; 11(10): 835. PMID: 26519361, PMCID: PMC4631206, ISSN: 1744-4292. 

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 ConsortiumJ Extracell Vesicles. 2015; 4: 27575. PMID: 26320942, PMCID: PMC4553260, PII: 27575, ISSN: 2001-3078. 

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 RNAJ Extracell Vesicles. 2015; 4: 27494. PMID: 26320939, PMCID: PMC4553266, PII: 27494, ISSN: 2001-3078. 

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 exosomesElife. 2015; 4: e07197. PMID: 26132860, PMCID: PMC4510696, DOI: 10.7554/eLife.07197, ISSN: 2050-084X. 

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 aggressivenessF1000Res. 2015; 4: 99. PMID: 26097693, PMCID: PMC4457132, DOI: 10.12688/f1000research.6388.1, ISSN: 2046-1402. 

Poulin EJ, Powell AE, Wang Y, Li Y, Franklin JL, Coffey RJUsing a new Lrig1 reporter mouse to assess differences between two Lrig1 antibodies in the intestineStem Cell Res [print-electronic]. 2014 Nov; 13(3 Pt A): 422-30. PMID: 25460603, PMCID: PMC4320017, PII: S1873-5061(14)00104-4, DOI: 10.1016/j.scr.2014.09.002, ISSN: 1876-7753. 

 

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