
Robert J. Coffey, M.D.
- Ingram Professor of Cancer Research
- Professor of Medicine (Gastroenterology, Hepatology and Nutrition)
- Professor of Cell and Developmental Biology
Phone
10415 MRB IV -0441
Nashville, TN 37232
Robert J. Coffey, M.D.
- Ingram Professor of Cancer Research
- Professor of Medicine (Gastroenterology, Hepatology and Nutrition)
- Professor of Cell and Developmental Biology
615-343-6228
robert.coffey@vumc.org
10415 MRB IV -0441
Nashville, TN 37232
Research Program
Departments/Affiliations
Profile
Education
- M.D., Georgetown University, Washington, District of Columbia (1976)
- A.B., Princeton University, Princeton, New Jersey (1970)
Research Emphasis
EGFR, EGFR Ligands, Vesicle Trafficking, Exosomes, 3-D Culture Systems, LRIG1 Intestinal Stem Cells, Colorectal Cancer, Long Non-Coding RNAs and Drug Resistance, Ménétrier’s Disease
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 gastrointestinal neoplasia. The lab has a particular interest in the trafficking of EGFR ligands in polarizing colonic epithelial cells. This work has led to the identification of a new mode of EGFR ligand signaling via exosomes and the development of FAVS (fluorescence-activated vesicle sorting) to isolate and characterize these extracellular vesicles. The lab discovered that Lrig1, an inducible negative regulator of the EGFR, marks proliferative and quiescent intestinal stem cells, and acts as a tumor suppressor. The lab has recently used CRISPR/Cas9 gene editing to make an Egfr-Emerald reporter mouse that enables direct visualization of the endogenous Egfr. Using a novel 3-D culture system, the lab recently identified a non-genetic cause of cetuximab resistance due to overexpression of a long non-coding RNA, MIR100HG, that confers cetuximab resistance due to increased WNT signaling.
Publications
- Banerjee A, McKinley ET, von Moltke J, Coffey RJ, Lau KS. Interpreting heterogeneity in intestinal tuft cell structure and function. J. Clin. Invest [print-electronic]. 2018 May 5/1/2018; 128(5): 1711-9. PMID: 29714721, PMCID: PMC5919882, PII: 120330, DOI: 10.1172/JCI120330, ISSN: 1558-8238.
- Saito-Diaz K, Benchabane H, Tiwari A, Tian A, Li B, Thompson JJ, Hyde AS, Sawyer LM, Jodoin JN, Santos E, Lee LA, Coffey RJ, Beauchamp RD, Williams CS, Kenworthy AK, Robbins DJ, Ahmed Y, Lee E. APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway. Dev. Cell. 2018 Mar 3/12/2018; 44(5): 566-581.e8. PMID: 29533772, PMCID: PMC5884143, PII: S1534-5807(18)30108-4, DOI: 10.1016/j.devcel.2018.02.013, ISSN: 1878-1551.
- Schulte ML, Fu A, Zhao P, Li J, Geng L, Smith ST, Kondo J, Coffey RJ, Johnson MO, Rathmell JC, Sharick JT, Skala MC, Smith JA, Berlin J, Washington MK, Nickels ML, Manning HC. Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models. Nat. Med [print-electronic]. 2018 Feb; 24(2): 194-202. PMID: 29334372, PMCID: PMC5803339, PII: nm.4464, DOI: 10.1038/nm.4464, ISSN: 1546-170X.
- Herring CA, Banerjee A, McKinley ET, Simmons AJ, Ping J, Roland JT, Franklin JL, Liu Q, Gerdes MJ, Coffey RJ, Lau KS. Unsupervised Trajectory Analysis of Single-Cell RNA-Seq and Imaging Data Reveals Alternative Tuft Cell Origins in the Gut. Cell Syst [print-electronic]. 2018 Jan 1/24/2018; 6(1): 37-51.e9. PMID: 29153838, PMCID: PMC5799016, PII: S2405-4712(17)30449-0, DOI: 10.1016/j.cels.2017.10.012, ISSN: 2405-4712.
- Herring CA, Banerjee A, McKinley ET, Simmons AJ, Ping J, Roland JT, Franklin JL, Liu Q, Gerdes MJ, Coffey RJ, Lau KS. Unsupervised Trajectory Analysis of Single-Cell RNA-Seq and Imaging Data Reveals Alternative Tuft Cell Origins in the Gut. Cell Syst [print-electronic]. 2018 Jan 1/24/2018; 6(1): 37-51.e9. PMID: 29153838, PMCID: PMC5799016, PII: S2405-4712(17)30449-0, DOI: 10.1016/j.cels.2017.10.012, ISSN: 2405-4712.
- Zhang Q, Jeppesen DK, Higginbotham JN, Demory Beckler M, Poulin EJ, Walsh AJ, Skala MC, McKinley ET, Manning HC, Hight MR, Schulte ML, Watt KR, Ayers GD, Wolf MM, Andrejeva G, Rathmell JC, Franklin JL, Coffey RJ. Mutant KRAS Exosomes Alter the Metabolic State of Recipient Colonic Epithelial Cells. Cell Mol Gastroenterol Hepatol. 2018; 5(4): 627-629.e6. PMID: 29930982, PMCID: PMC6009797, PII: S2352-345X(18)30020-1, DOI: 10.1016/j.jcmgh.2018.01.013, ISSN: 2352-345X.
- Means AL, Freeman TJ, Zhu J, Woodbury LG, Marincola-Smith P, Wu C, Meyer AR, Weaver CJ, Padmanabhan C, An H, Zi J, Wessinger BC, Chaturvedi R, Brown TD, Deane NG, Coffey RJ, Wilson KT, Smith JJ, Sawyers CL, Goldenring JR, Novitskiy SV, Washington MK, Shi C, Beauchamp RD. Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer. Cell Mol Gastroenterol Hepatol. 2018; 6(3): 257-76. PMID: 30109253, PMCID: PMC6083016, PII: S2352-345X(18)30082-1, DOI: 10.1016/j.jcmgh.2018.05.006, ISSN: 2352-345X.
- Short SP, Kondo J, Smalley-Freed WG, Takeda H, Dohn MR, Powell AE, Carnahan RH, Washington MK, Tripathi M, Payne DM, Jenkins NA, Copeland NG, Coffey RJ, Reynolds AB. P120-Catenin is an obligate haploinsufficient tumor suppressor in intestinal neoplasia. J. Clin. Invest [print-electronic]. 2017 Dec 12/1/2017; 127(12): 4462-76. PMID: 29130932, PMCID: PMC5707165, PII: 77217, DOI: 10.1172/JCI77217, ISSN: 1558-8238.
- Short SP, Kondo J, Smalley-Freed WG, Takeda H, Dohn MR, Powell AE, Carnahan RH, Washington MK, Tripathi M, Payne DM, Jenkins NA, Copeland NG, Coffey RJ, Reynolds AB. P120-Catenin is an obligate haploinsufficient tumor suppressor in intestinal neoplasia. J. Clin. Invest [print-electronic]. 2017 Dec 12/1/2017; 127(12): 4462-76. PMID: 29130932, PMCID: PMC5707165, PII: 77217, DOI: 10.1172/JCI77217, ISSN: 1558-8238.
- Lu Y, Zhao X, Liu Q, Li C, Graves-Deal R, Cao Z, Singh B, Franklin JL, Wang J, Hu H, Wei T, Yang M, Yeatman TJ, Lee E, Saito-Diaz K, Hinger S, Patton JG, Chung CH, Emmrich S, Klusmann JH, Fan D, Coffey RJ. LncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/ß-catenin signaling. Nat. Med [print-electronic]. 2017 Oct 10/16/2017; PMID: 29035371, PII: nm.4424, DOI: 10.1038/nm.4424, ISSN: 1546-170X.