Robert J. Coffey, Jr

Ingram Professor of Cancer Research

Professor of Medicine


Division

Gastroenterology, Hepatology and Nutrition

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

Robert J. Coffey, Jr


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 

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 vivo. Mol. Syst. Biol. 2015; 11(10): 835. PMID: 26519361, PMCID: PMC4631206, ISSN: 1744-4292. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26519361., 2015.

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. 2015; 4: e07197. PMID: 26132860, PMCID: PMC4510696, DOI: 10.7554/eLife.07197, ISSN: 2050-084X. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26132860., 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. 2015; 4: 99. PMID: 26097693, PMCID: PMC4457132, DOI: 10.12688/f1000research.6388.1, ISSN: 2046-1402. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26097693., 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. 2015; 4: 27494. PMID: 26320939, PMCID: PMC4553266, PII: 27494, ISSN: 2001-3078. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26320939., 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. 2015; 4: 27575. PMID: 26320942, PMCID: PMC4553260, PII: 27575, ISSN: 2001-3078. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26320942., 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. 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. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25794708., 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 [print-electronic]. 2015 Apr 4/24/2015; PMID: 25913616, PMCID: PMC4619179, DOI: 10.1111/his.12725, ISSN: 1365-2559. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25913616., 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 [print-electronic]. 2015 Jul; 29(6): 535-42. PMID: 25899481, PMCID: PMC4503488, DOI: 10.1007/s12149-015-0974-6, ISSN: 1864-6433. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25899481., 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 [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. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25921371., 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 [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. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26272915., 2015.

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. 2014; 9(9): e108193. PMID: 25247710, PMCID: PMC4172755, PII: PONE-D-14-08668, DOI: 10.1371/journal.pone.0108193, ISSN: 1932-6203. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25247710., 2014.

Singh B, Coffey RJ. Trafficking of epidermal growth factor receptor ligands in polarized epithelial cells. Annu. Rev. Physiol [print-electronic]. 2014; 76: 275-300. PMID: 24215440, PMCID: PMC4180094, DOI: 10.1146/annurev-physiol-021113-170406, ISSN: 1545-1585. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24215440., 2014.

Ray KC, Moss ME, Franklin JL, Weaver CJ, Higginbotham J, Song Y, Revetta FL, Blaine SA, Bridges LR, Guess KE, Coffey RJ, Crawford HC, Washington MK, Means AL. Heparin-binding epidermal growth factor-like growth factor eliminates constraints on activated Kras to promote rapid onset of pancreatic neoplasia. Oncogene [print-electronic]. 2014 Feb 2/13/2014; 33(7): 823-31. PMID: 23376846, PMCID: PMC3929321, PII: onc20133, DOI: 10.1038/onc.2013.3, ISSN: 1476-5594. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23376846., 2014.

Singh B, Coffey RJ. From wavy hair to naked proteins: the role of transforming growth factor alpha in health and disease. Semin. Cell Dev. Biol [print-electronic]. 2014 Apr; 28: 12-21. PMID: 24631356, PMCID: PMC4105142, PII: S1084-9521(14)00031-7, DOI: 10.1016/j.semcdb.2014.03.003, ISSN: 1096-3634. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24631356., 2014.

Hight MR, Cheung YY, Nickels ML, Dawson ES, Zhao P, Saleh S, Buck JR, Tang D, Washington MK, Coffey RJ, Manning HC. A peptide-based positron emission tomography probe for in vivo detection of caspase activity in apoptotic cells. Clin. Cancer Res [print-electronic]. 2014 Apr 4/15/2014; 20(8): 2126-35. PMID: 24573549, PMCID: PMC3989451, PII: 1078-0432.CCR-13-2444, DOI: 10.1158/1078-0432.CCR-13-2444, ISSN: 1078-0432. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24573549., 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 [print-electronic]. 2014 May; 124(5): 2172-87. PMID: 24691442, PMCID: PMC4001536, PII: 71103, DOI: 10.1172/JCI71103, ISSN: 1558-8238. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24691442., 2014.

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 TGFß signaling to modify vascular pathology in mice and humans. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2014 May 5/27/2014; 111(21): 7723-8. PMID: 24812125, PMCID: PMC4040598, PII: 1318761111, DOI: 10.1073/pnas.1318761111, ISSN: 1091-6490. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24812125., 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 [print-electronic]. 2014 Jul 7/1/2014; 307(1): G16-23. PMID: 24833705, PMCID: PMC4080164, PII: ajpgi.00358.2013, DOI: 10.1152/ajpgi.00358.2013, ISSN: 1522-1547. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24833705., 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 [print-electronic]. 2014 Sep 9/1/2014; 25(17): 2592-603. PMID: 25009281, PMCID: PMC4148249, PII: mbc.E13-08-0492, DOI: 10.1091/mbc.E13-08-0492, ISSN: 1939-4586. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25009281., 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 [print-electronic]. 2014 Sep 9/18/2014; 513(7518): 382-7. PMID: 25043054, PMCID: PMC4249766, PII: nature13438, DOI: 10.1038/nature13438, ISSN: 1476-4687. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25043054., 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 [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. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25460603., 2014.

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