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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 

Jeffrey L. Franklin, Ph.D.

Research Assistant Professor of Medicine
Researcher

Contact Information:

Vanderbilt University Medical Center
10415 Medical Research Building IV
Nashville, TN 37232
615-343-6264

Profile

A large focus of my work is on the normal function of the intestine and how progenitor cell relationships change during GI disease processies like cancer and inflammatory damage. Relevant to this basic research area, I am the director of the cell development subcore of the DDRC.
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A large focus of my work is on the normal function of the intestine and how progenitor cell relationships change during GI disease processies like cancer and inflammatory damage. Relevant to this basic research area, I am the director of the cell development subcore of the DDRC. In this core we develop new normal, conditionally immortalized, mouse epithelial cell lines from various mouse models and human tissue. These cell lines have been made for members of the Vanderbilt Community as well as for other labs around the country and world.

A major focus of my work concerns the function of cell secreted vesicles called exosomes. In ongoing studies we have found that EGFR ligands are in exosomes represent a new and unique way to activate EGFR that influences tumor cell growth and metastasis in a different way than other ligand presentation mechanisms. An integral area of my research concerns the role that non-coding RNAs (miRNAs and long-non-coding) have in influencing stem cell and altered neoplastic signals. We have seen that ncRNAs can act to regulate growth of normal intestinal cells and when overexpressed can lead to invasive cancers by regulating miRNA function. We have found that exosomes carry numerous miRNAs, mRNAs and long non-coding RNAs and their trafficking to exosomes is regulated by mutant oncogenic KRAS. This area of research has the potential to increase our understanding of how tumors affect their microenvironment, how they may signal to the metastatic niche and also hold great promise for biomarker research. 

We are also interested in the genes that control intestinal stem cell growth and differentiation and how abnormal signaling in CRC is associated with alterations in stem cell gene function, including modulators of EGFR function. These include negative regulators of EGFR as well as Wnt signaling components, as there is crosstalk between EGFR and Wnt signaling. Other areas of research include a collaboration between our lab and GE to use the GE MultiOmyxâ„¢ system to perform microscopic imaging of individual tissue sections with fluorescence microscopy, using up to 100 antibody stains for each individual section. Antibody staining of individual cells in multiple images is all registered allowing single cell analysis that provides an expression landscape within an in situ tissue microenvironment. 

Education
  • B.A. Haverford College (Maj. Chemistry)
  • Ph.D. Vanderbilt University (Dept. of Molecular Biology)
 
Publications
  • McKenzie AJ, Hoshino D, Hong NH, Cha DJ, Franklin JL, Coffey RJ, Patton JG, Weaver AM. KRAS-MEK Signaling Controls Ago2 Sorting into Exosomes. Cell 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/27117408.
  • Higginbotham JN, Zhang Q, Jeppesen DK, Scott AM, Manning HC, Ochieng J, Franklin JL, Coffey RJ. Identification and characterization of EGF receptor in individual exosomes by fluorescence-activated vesicle sorting. J Extracell Vesicles. 2016; 5: 29254. PMID: 27345057, PII: 29254, ISSN: 2001-3078.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/27345057.
  • 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 Oct; 11(10): 835. PMID: 26519361, PMCID: PMC4631206, ISSN: 1744-4292.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26519361.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Farrow MA, Chumbler NM, Lapierre LA, Franklin JL, Rutherford SA, Goldenring JR, Lacy DB. Clostridium difficile toxin B-induced necrosis is mediated by the host epithelial cell NADPH oxidase complex. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Nov 11/12/2013; 110(46): 18674-9. PMID: 24167244, PMCID: PMC3831945, PII: 1313658110, DOI: 10.1073/pnas.1313658110, ISSN: 1091-6490.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24167244.
  • Franklin JL, Rankin CR, Levy S, Snoddy JR, Zhang B, Washington MK, Thomson JM, Whitehead RH, Coffey RJ. Malignant transformation of colonic epithelial cells by a colon-derived long noncoding RNA. Biochem. Biophys. Res. Commun [print-electronic]. 2013 Oct 10/11/2013; 440(1): 99-104. PMID: 24045012, PMCID: PMC3875348, PII: S0006-291X(13)01511-8, DOI: 10.1016/j.bbrc.2013.09.040, ISSN: 1090-2104.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24045012.
  • Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol. Cell Proteomics [print-electronic]. 2013 Feb; 12(2): 343-55. PMID: 23161513, PMCID: PMC3567858, PII: M112.022806, DOI: 10.1074/mcp.M112.022806, ISSN: 1535-9484.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23161513.
  • Zhu J, Wang J, Shi Z, Franklin JL, Deane NG, Coffey RJ, Beauchamp RD, Zhang B. Deciphering genomic alterations in colorectal cancer through transcriptional subtype-based network analysis. PLoS ONE. 2013; 8(11): e79282. PMID: 24260186, PMCID: PMC3829853, PII: PONE-D-13-34057, DOI: 10.1371/journal.pone.0079282, ISSN: 1932-6203.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24260186.
  • Kim TI, Poulin EJ, Blask E, Bukhalid R, Whitehead RH, Franklin JL, Coffey RJ. Myofibroblast keratinocyte growth factor reduces tight junctional integrity and increases claudin-2 levels in polarized Caco-2 cells. Growth Factors [print-electronic]. 2012 Oct; 30(5): 320-32. PMID: 22946653, PMCID: PMC3594790, DOI: 10.3109/08977194.2012.717076, ISSN: 1029-2292.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22946653.
  • 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. 2012 Mar 3/30/2012; 149(1): 146-58. PMID: 22464327, PMCID: PMC3563328, PII: S0092-8674(12)00280-2, DOI: 10.1016/j.cell.2012.02.042, ISSN: 1097-4172.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22464327.
  • Chumbler NM, Farrow MA, Lapierre LA, Franklin JL, Haslam DB, Goldenring JR, Lacy DB. Clostridium difficile Toxin B causes epithelial cell necrosis through an autoprocessing-independent mechanism. PLoS Pathog [print-electronic]. 2012; 8(12): e1003072. PMID: 23236283, PMCID: PMC3516567, PII: PPATHOGENS-D-12-01408, DOI: 10.1371/journal.ppat.1003072, ISSN: 1553-7374.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23236283.
  • Gephart JD, Singh B, Higginbotham JN, Franklin JL, Gonzalez A, Fölsch H, Coffey RJ. Identification of a novel mono-leucine basolateral sorting motif within the cytoplasmic domain of amphiregulin. Traffic [print-electronic]. 2011 Dec; 12(12): 1793-804. PMID: 21917092, PMCID: PMC3886124, DOI: 10.1111/j.1600-0854.2011.01282.x, ISSN: 1600-0854.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21917092.
  • 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 [print-electronic]. 2011 May 5/10/2011; 21(9): 779-86. PMID: 21514161, PMCID: PMC3417320, PII: S0960-9822(11)00347-2, DOI: 10.1016/j.cub.2011.03.043, ISSN: 1879-0445.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21514161.
  • Van Raay TJ, Fortino NJ, Miller BW, Ma H, Lau G, Li C, Franklin JL, Attisano L, Solnica-Krezel L, Coffey RJ. Naked1 antagonizes Wnt signaling by preventing nuclear accumulation of ß-catenin. PLoS ONE. 2011; 6(4): e18650. PMID: 21490931, PMCID: PMC3072412, DOI: 10.1371/journal.pone.0018650, ISSN: 1932-6203.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21490931.
  • Wang L, Chen X, Wolfinger RD, Franklin JL, Coffey RJ, Zhang B. A unified mixed effects model for gene set analysis of time course microarray experiments. Stat Appl Genet Mol Biol [print-electronic]. 2009; 8: Article 47. PMID: 19954419, PMCID: PMC2861317, DOI: 10.2202/1544-6115.1484, ISSN: 1544-6115.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/19954419.
  • 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 proteomics analysis. Mol. Cell Proteomics [print-electronic]. 2008 Sep; 7(9): 1651-67. PMID: 18504258, PMCID: PMC2528074, PII: M700155-MCP200, DOI: 10.1074/mcp.M700155-MCP200, ISSN: 1535-9484.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18504258.
  • Whitehead RH, Robinson PS, Williams JA, Bie W, Tyner AL, Franklin JL. Conditionally immortalized colonic epithelial cell line from a Ptk6 null mouse that polarizes and differentiates in vitro. J. Gastroenterol. Hepatol [print-electronic]. 2008 Jul; 23(7 Pt 1): 1119-24. PMID: 18205771, PMCID: PMC3005200, PII: JGH5308, DOI: 10.1111/j.1440-1746.2008.05308.x, ISSN: 1440-1746.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18205771.
  • Tahinci E, Thorne CA, Franklin JL, Salic A, Christian KM, Lee LA, Coffey RJ, Lee E. Lrp6 is required for convergent extension during Xenopus gastrulation. Development. 2007 Nov; 134(22): 4095-106. PMID: 17965054, PMCID: PMC4428168, PII: 134/22/4095, DOI: 10.1242/dev.010272, ISSN: 0950-1991.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17965054.
  • Keller JW, Haigis KM, Franklin JL, Whitehead RH, Jacks T, Coffey RJ. Oncogenic K-RAS subverts the antiapoptotic role of N-RAS and alters modulation of the N-RAS:gelsolin complex. Oncogene [print-electronic]. 2007 May 5/10/2007; 26(21): 3051-9. PMID: 17130841, PII: 1210103, DOI: 10.1038/sj.onc.1210103, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17130841.
  • Keller JW, Franklin JL, Graves-Deal R, Friedman DB, Whitwell CW, Coffey RJ. Oncogenic KRAS provides a uniquely powerful and variable oncogenic contribution among RAS family members in the colonic epithelium. J. Cell. Physiol. 2007 Mar; 210(3): 740-9. PMID: 17133351, DOI: 10.1002/jcp.20898, ISSN: 0021-9541.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17133351.
  • Amann JM, Chyla BJ, Ellis TC, Martinez A, Moore AC, Franklin JL, McGhee L, Meyers S, Ohm JE, Luce KS, Ouelette AJ, Washington MK, Thompson MA, King D, Gautam S, Coffey RJ, Whitehead RH, Hiebert SW. Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine. Mol. Cell. Biol. 2005 Nov; 25(21): 9576-85. PMID: 16227606, PMCID: PMC1265807, PII: 25/21/9576, DOI: 10.1128/MCB.25.21.9576-9585.2005, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16227606.
  • Chung E, Graves-Deal R, Franklin JL, Coffey RJ. Differential effects of amphiregulin and TGF-alpha on the morphology of MDCK cells. Exp. Cell Res. 2005 Sep 9/10/2005; 309(1): 149-60. PMID: 15979068, PII: S0014-4827(05)00243-0, DOI: 10.1016/j.yexcr.2005.05.012, ISSN: 0014-4827.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15979068.
  • Franklin JL, Yoshiura K, Dempsey PJ, Bogatcheva G, Jeyakumar L, Meise KS, Pearsall RS, Threadgill D, Coffey RJ. Identification of MAGI-3 as a transforming growth factor-alpha tail binding protein. Exp. Cell Res. 2005 Feb 2/15/2005; 303(2): 457-70. PMID: 15652357, PII: S0014-4827(04)00612-3, DOI: 10.1016/j.yexcr.2004.10.007, ISSN: 0014-4827.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15652357.
  • Park YK, Franklin JL, Settle SH, Levy SE, Chung E, Jeyakumar LH, Shyr Y, Washington MK, Whitehead RH, Aronow BJ, Coffey RJ. Gene expression profile analysis of mouse colon embryonic development. Genesis. 2005 Jan; 41(1): 1-12. PMID: 15645444, DOI: 10.1002/gene.20088, ISSN: 1526-954X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15645444.
  • 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 [print-electronic]. 2004 Apr 4/13/2004; 101(15): 5571-6. PMID: 15064403, PMCID: PMC397424, PII: 0401294101, DOI: 10.1073/pnas.0401294101, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15064403.
  • Franklin JL, Haseltine D, Davenport L, Mosig G. The largest (70 kDa) product of the bacteriophage T4 DNA terminase gene 17 binds to single-stranded DNA segments and digests them towards junctions with double-stranded DNA. J. Mol. Biol. 1998 Apr 4/3/1998; 277(3): 541-57. PMID: 9533879, PII: S0022-2836(98)91619-9, DOI: 10.1006/jmbi.1998.1619, ISSN: 0022-2836.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9533879.
  • Franklin JL, Mosig G. Expression of the bacteriophage T4 DNA terminase genes 16 and 17 yields multiple proteins. Gene. 1996 Oct 10/24/1996; 177(1-2): 179-89. PMID: 8921865, ISSN: 0378-1119.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8921865.