Christopher S. Williams, Ph.D., M.D.

Associate Professor

christopher.s.williams@vanderbilt.edu

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Faculty Appointments
Associate Professor of Medicine Associate Professor of Cancer Biology
Education
M.D., Medicine, Vanderbilt University, Nashville, TennesseePh.D., Cell Biology, Vanderbilt University, Nashville, TennesseeB.Sc., Molecular Biology, Brigham Young University, Provo, Utah
Office Address
Gastroenterology Division -
1030-C Medical Research Building IV -
2215 Garland Avenue -
Nashville, TN 37232-0252
Research Description
Our research program focuses on understanding how the epithelium responds to injury and how normal injury response processes are subverted in the development of malignancy. The research activities span the basic to translational spectrum. We have three major research programs within the lab:

<b>1) Epigenetic control of intestinal epithelial wound healing and repair programs and relationship to colorectal oncogenesis. </b>
We are studying the role of the Myeloid Translocation Gene (MTGs) family in intestinal biology with emphasis on gut development, stem cell function, wound healing and malignancy. MTGR1 (Myeloid Translocation Gene, Related-1), MTG8 and MTG16 are members of a gene family originally identified as targets of chromosomal translocation in acute myeloid leukemia (AML). MTG family members act as transcriptional repressors and interact with other corepressors mSin3, N-CoR/SMRT and histone deacetylases (HDAC1-3). Chromosomal translocations often target master regulatory genes that affect growth, differentiation and apoptosis.

Using unique mouse models we are characterizing MTGs as modifiers of WNT dependent tumorigenesis in the gut and deterring how the regulate stem cell programs.

<b>2) Junctional signaling in mucosal wound healing responses and inflammatory carcinogenesis. </b>
We recently determined that a tight junction associated protein called BVES was suppressed by promoter methylation in colon cancer and that it regulates epithelial to mesenchymal transition (EMT) influencing metastasis.

We are currently cataloging the BVES protein interactome as a means to understand how BVES transduces "Out to In" signaling. In addition, using <i>Bves</i>-null mice, we are dissecting its role in intestinal wound healing using chemical, infectious, and mechanical colonic injury modeling and its role in colitis associated cancer.

<b> 3) Oxidative injury defenses in Inflammatory Bowel Disease (IBD) and colitis associated carcinoma (CAC). </b>
Little is known about the role of selenium and selenoproteins in inflammatory bowel disease (IBD), a condition of intermittent severe oxidative stress. We have shown that selenium deficiency results in increased mucosal injury and progression to colitis-associated dysplasia (CAD). Likewise, germ line Sepp1 and Gpx3 mutant mice had increased tumor burden with major effects on proliferation, apoptosis and DNA damage.

We hypothesize that intestinal Sepp1 alters the inflammatory microenvironment via clearance of reactive oxygen species thus affecting epithelial stem cell and differentiation programs. We are determining which stem cell pathways are modified by selenoproteins in influencing tumorigenesis.
Research Keywords
1) Epigenetic control of intestinal epithelial wound healing and repair programs and relationship to colorectal oncogenesis. 2) Junctional signaling in mucosal wound healing responses and inflammatory carcinogenesis. 3) Oxidative injury defenses in Inflammatory Bowel Disease (IBD) and colitis associated carcinoma (CAC).
Clinical Research Keywords
Inflammatory Bowel Disease Inflammational Carcinogenesis
Publications
Williams CS, Bernard JK, Demory Beckler M, Almohazey D, Washington MK, Smith JJ, Frey MR. ERBB4 is over-expressed in human colon cancer and enhances cellular transformation. Carcinogenesis [print-electronic]. 2015 Jul; 36(7): 710-8. PMID: 25916654, PMCID: PMC4572918, PII: bgv049, DOI: 10.1093/carcin/bgv049, ISSN: 1460-2180.

Barrett CW, Reddy VK, Short SP, Motley AK, Lintel MK, Bradley AM, Freeman T, Vallance J, Ning W, Parang B, Poindexter SV, Fingleton B, Chen X, Washington MK, Wilson KT, Shroyer NF, Hill KE, Burk RF, Williams CS. Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage. J. Clin. Invest [print-electronic]. 2015 Jul 7/1/2015; 125(7): 2646-60. PMID: 26053663, PMCID: PMC4563672, PII: 76099, DOI: 10.1172/JCI76099, ISSN: 1558-8238.

Poindexter SV, Reddy VK, Mittal MK, Williams AM, Washington MK, Harris E, Mah A, Hiebert SW, Singh K, Chaturvedi R, Wilson KT, Lund PK, Williams CS. Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation and crypt regeneration after radiation-induced injury. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2015 Mar 3/15/2015; 308(6): G562-71. PMID: 25573176, PMCID: PMC4360050, PII: ajpgi.00253.2014, DOI: 10.1152/ajpgi.00253.2014, ISSN: 1522-1547.

Parang B, Rosenblatt D, Williams AD, Washington MK, Revetta F, Short SP, Reddy VK, Hunt A, Shroyer NF, Engel ME, Hiebert SW, Williams CS. The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation. FASEB J [print-electronic]. 2015 Mar; 29(3): 786-95. PMID: 25398765, PII: fj.14-254284, DOI: 10.1096/fj.14-254284, ISSN: 1530-6860.

Williams CS, Bradley AM, Chaturvedi R, Singh K, Piazuelo MB, Chen X, McDonough EM, Schwartz DA, Brown CT, Allaman MM, Coburn LA, Horst SN, Beaulieu DB, Choksi YA, Washington MK, Williams AD, Fisher MA, Zinkel SS, Peek RM, Wilson KT, Hiebert SW. MTG16 contributes to colonic epithelial integrity in experimental colitis. Gut [print-electronic]. 2013 Oct; 62(10): 1446-55. PMID: 22833394, PMCID: PMC3663894, PII: gutjnl-2011-301439, DOI: 10.1136/gutjnl-2011-301439, ISSN: 1468-3288.

Singh K, Coburn LA, Barry DP, Asim M, Scull BP, Allaman MM, Lewis ND, Washington MK, Rosen MJ, Williams CS, Chaturvedi R, Wilson KT. Deletion of cationic amino acid transporter 2 exacerbates dextran sulfate sodium colitis and leads to an IL-17-predominant T cell response. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2013 Aug 8/1/2013; 305(3): G225-40. PMID: 23703655, PMCID: PMC3742860, PII: ajpgi.00091.2013, DOI: 10.1152/ajpgi.00091.2013, ISSN: 1522-1547.

Rosen MJ, Chaturvedi R, Washington MK, Kuhnhein LA, Moore PD, Coggeshall SS, McDonough EM, Weitkamp JH, Singh AB, Coburn LA, Williams CS, Yan F, Van Kaer L, Peebles RS, Wilson KT. STAT6 deficiency ameliorates severity of oxazolone colitis by decreasing expression of claudin-2 and Th2-inducing cytokines. J. Immunol [print-electronic]. 2013 Feb 2/15/2013; 190(4): 1849-58. PMID: 23303670, PMCID: PMC3563924, PII: jimmunol.1201373, DOI: 10.4049/jimmunol.1201373, ISSN: 1550-6606.

Barrett CW, Ning W, Chen X, Smith JJ, Washington MK, Hill KE, Coburn LA, Peek RM, Chaturvedi R, Wilson KT, Burk RF, Williams CS. Tumor suppressor function of the plasma glutathione peroxidase gpx3 in colitis-associated carcinoma. Cancer Res [print-electronic]. 2013 Feb 2/1/2013; 73(3): 1245-55. PMID: 23221387, PMCID: PMC3563732, PII: 0008-5472.CAN-12-3150, DOI: 10.1158/0008-5472.CAN-12-3150, ISSN: 1538-7445.

Coburn LA, Horst SN, Chaturvedi R, Brown CT, Allaman MM, Scull BP, Singh K, Piazuelo MB, Chitnavis MV, Hodges ME, Rosen MJ, Williams CS, Slaughter JC, Beaulieu DB, Schwartz DA, Wilson KT. High-throughput multi-analyte Luminex profiling implicates eotaxin-1 in ulcerative colitis. PLoS ONE. 2013; 8(12): e82300. PMID: 24367513, PMCID: PMC3867379, PII: PONE-D-13-38373, DOI: 10.1371/journal.pone.0082300, ISSN: 1932-6203.

Barrett CW, Singh K, Motley AK, Lintel MK, Matafonova E, Bradley AM, Ning W, Poindexter SV, Parang B, Reddy VK, Chaturvedi R, Fingleton BM, Washington MK, Wilson KT, Davies SS, Hill KE, Burk RF, Williams CS. Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis. PLoS ONE [electronic-print]. 2013; 8(7): e67845. PMID: 23861820, PMCID: PMC3701622, PII: PONE-D-13-14817, DOI: 10.1371/journal.pone.0067845, ISSN: 1932-6203.

Coburn LA, Gong X, Singh K, Asim M, Scull BP, Allaman MM, Williams CS, Rosen MJ, Washington MK, Barry DP, Piazuelo MB, Casero RA, Chaturvedi R, Zhao Z, Wilson KT. L-arginine supplementation improves responses to injury and inflammation in dextran sulfate sodium colitis. PLoS ONE [print-electronic]. 2012; 7(3): e33546. PMID: 22428068, PMCID: PMC3299802, PII: PONE-D-12-00729, DOI: 10.1371/journal.pone.0033546, ISSN: 1932-6203.

Barrett CW, Smith JJ, Lu LC, Markham N, Stengel KR, Short SP, Zhang B, Hunt AA, Fingleton BM, Carnahan RH, Engel ME, Chen X, Beauchamp RD, Wilson KT, Hiebert SW, Reynolds AB, Williams CS. Kaiso directs the transcriptional corepressor MTG16 to the Kaiso binding site in target promoters. PLoS ONE [print-electronic]. 2012; 7(12): e51205. PMID: 23251453, PMCID: PMC3521008, PII: PONE-D-12-22965, DOI: 10.1371/journal.pone.0051205, ISSN: 1932-6203.

Williams CS, Zhang B, Smith JJ, Jayagopal A, Barrett CW, Pino C, Russ P, Presley SH, Peng D, Rosenblatt DO, Haselton FR, Yang JL, Washington MK, Chen X, Eschrich S, Yeatman TJ, El-Rifai W, Beauchamp RD, Chang MS. BVES regulates EMT in human corneal and colon cancer cells and is silenced via promoter methylation in human colorectal carcinoma. J. Clin. Invest [print-electronic]. 2011 Oct; 121(10): 4056-69. PMID: 21911938, PMCID: PMC3195453, PII: 44228, DOI: 10.1172/JCI44228, ISSN: 1558-8238.

Barrett CW, Fingleton B, Williams A, Ning W, Fischer MA, Washington MK, Chaturvedi R, Wilson KT, Hiebert SW, Williams CS. MTGR1 is required for tumorigenesis in the murine AOM/DSS colitis-associated carcinoma model. Cancer Res [print-electronic]. 2011 Feb 2/15/2011; 71(4): 1302-12. PMID: 21303973, PMCID: PMC3150168, PII: 0008-5472.CAN-10-3317, DOI: 10.1158/0008-5472.CAN-10-3317, ISSN: 1538-7445.

Russ PK, Pino CJ, Williams CS, Bader DM, Haselton FR, Chang MS. Bves modulates tight junction associated signaling. PLoS ONE. 2011; 6(1): e14563. PMID: 21283798, PMCID: PMC3024319, DOI: 10.1371/journal.pone.0014563, ISSN: 1932-6203.

Hong SK, Chaturvedi R, Piazuelo MB, Coburn LA, Williams CS, Delgado AG, Casero RA, Schwartz DA, Wilson KT. Increased expression and cellular localization of spermine oxidase in ulcerative colitis and relationship to disease activity. Inflamm. Bowel Dis. 2010 Sep; 16(9): 1557-66. PMID: 20127992, PMCID: PMC2894261, DOI: 10.1002/ibd.21224, ISSN: 1536-4844.

Whittem CG, Williams AD, Williams CS. Murine Colitis modeling using Dextran Sulfate Sodium (DSS). J Vis Exp. 2010; (35): PMID: 20087313, PMCID: PMC2841571, PII: 1652, DOI: 10.3791/1652, ISSN: 1940-087X.

Farmer TE, Williams CS, Washington MK, Hiebert SW. Inactivation of the p19(ARF) tumor suppressor affects intestinal epithelial cell proliferation and integrity. J. Cell. Biochem. 2008 Aug 8/15/2008; 104(6): 2228-40. PMID: 18442038, PMCID: PMC3164503, DOI: 10.1002/jcb.21779, ISSN: 1097-4644.

Moore AC, Amann JM, Williams CS, Tahinci E, Farmer TE, Martinez JA, Yang G, Luce KS, Lee E, Hiebert SW. Myeloid translocation gene family members associate with T-cell factors (TCFs) and influence TCF-dependent transcription. Mol. Cell. Biol [print-electronic]. 2008 Feb; 28(3): 977-87. PMID: 18039847, PMCID: PMC2223385, PII: MCB.01242-07, DOI: 10.1128/MCB.01242-07, ISSN: 1098-5549.

Martinez JA, Williams CS, Amann JM, Ellis TC, Moreno-Miralles I, Washington MK, Gregoli P, Hiebert SW. Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis. Gastroenterology. 2006 Aug; 131(2): 579-88. PMID: 16890610, PII: S0016-5085(06)01238-8, DOI: 10.1053/j.gastro.2006.06.009, ISSN: 0016-5085.

Smith DS, Williams CS, Ferris CD. Diagnosis and treatment of chronic gastroparesis and chronic intestinal pseudo-obstruction. Gastroenterol. Clin. North Am. 2003 Jun; 32(2): 619-58. PMID: 12858609, ISSN: 0889-8553.

Aklog L, Williams CS, Byrne JG, Goldhaber SZ. Acute pulmonary embolectomy: a contemporary approach. Circulation. 2002 Mar 3/26/2002; 105(12): 1416-9. PMID: 11914247, ISSN: 1524-4539.

Williams CS, Sheng H, Brockman JA, Armandla R, Shao J, Washington MK, Elkahloun AG, DuBois RN. A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. Neoplasia. 2001 Sep; 3(5): 428-36. PMID: 11687954, PMCID: PMC1506203, ISSN: 1522-8002.

Mann M, Sheng H, Shao J, Williams CS, Pisacane PI, Sliwkowski MX, DuBois RN. Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology. 2001 Jun; 120(7): 1713-9. PMID: 11375952, PII: S0016508501646870, ISSN: 0016-5085.

Williams CS, Watson AJ, Sheng H, Helou R, Shao J, DuBois RN. Celecoxib prevents tumor growth in vivo without toxicity to normal gut: lack of correlation between in vitro and in vivo models. Cancer Res. 2000 Nov 11/1/2000; 60(21): 6045-51. PMID: 11085526, ISSN: 0008-5472.

Callejas NA, Boscá L, Williams CS, DuBOIS RN, Martín-Sanz P. Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins. Gastroenterology. 2000 Aug; 119(2): 493-501. PMID: 10930384, PII: S0016508500494680, ISSN: 0016-5085.

Williams CS, Tsujii M, Reese J, Dey SK, DuBois RN. Host cyclooxygenase-2 modulates carcinoma growth. J. Clin. Invest. 2000 Jun; 105(11): 1589-94. PMID: 10841517, PMCID: PMC300858, DOI: 10.1172/JCI9621, ISSN: 0021-9738.

Sheng H, Shao J, Dixon DA, Williams CS, Prescott SM, DuBois RN, Beauchamp RD. Transforming growth factor-beta1 enhances Ha-ras-induced expression of cyclooxygenase-2 in intestinal epithelial cells via stabilization of mRNA. J. Biol. Chem. 2000 Mar 3/3/2000; 275(9): 6628-35. PMID: 10692471, ISSN: 0021-9258.

Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 1999 Dec 12/20/1999; 18(55): 7908-16. PMID: 10630643, DOI: 10.1038/sj.onc.1203286, ISSN: 0950-9232.

Williams CS, Goldman AP, Sheng H, Morrow JD, DuBois RN. Sulindac sulfide, but not sulindac sulfone, inhibits colorectal cancer growth. Neoplasia. 1999 Jun; 1(2): 170-6. PMID: 10933052, PMCID: PMC1508136, ISSN: 1522-8002.

Williams CS, Shattuck-Brandt RL, DuBois RN. The role of COX-2 in intestinal cancer. Expert Opin Investig Drugs. 1999 Jan; 8(1): 1-12. PMID: 15992053, DOI: 10.1517/13543784.8.1.1, ISSN: 1744-7658.

Goldman AP, Williams CS, Sheng H, Lamps LW, Williams VP, Pairet M, Morrow JD, DuBois RN. Meloxicam inhibits the growth of colorectal cancer cells. Carcinogenesis. 1998 Dec; 19(12): 2195-9. PMID: 9886578, ISSN: 0143-3334.

Sheng H, Williams CS, Shao J, Liang P, DuBois RN, Beauchamp RD. Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts and the role of mitogen-activated protein kinase pathway. J. Biol. Chem. 1998 Aug 8/21/1998; 273(34): 22120-7. PMID: 9705357, ISSN: 0021-9258.

Sheng H, Shao J, Williams CS, Pereira MA, Taketo MM, Oshima M, Reynolds AB, Washington MK, DuBois RN, Beauchamp RD. Nuclear translocation of beta-catenin in hereditary and carcinogen-induced intestinal adenomas. Carcinogenesis. 1998 Apr; 19(4): 543-9. PMID: 9600336, ISSN: 0143-3334.

Williams CS, Smalley W, DuBois RN. Aspirin use and potential mechanisms for colorectal cancer prevention. J. Clin. Invest. 1997 Sep 9/15/1997; 100(6): 1325-9. PMID: 9294096, PMCID: PMC508309, DOI: 10.1172/JCI119651, ISSN: 0021-9738.

Zhang T, Nanney LB, Peeler MO, Williams CS, Lamps L, Heppner KJ, DuBois RN, Beauchamp RD. Decreased transforming growth factor beta type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression. Cancer Res. 1997 May 5/1/1997; 57(9): 1638-43. PMID: 9134999, ISSN: 0008-5472.

Inoue I, Nakajima T, Williams CS, Quackenbush J, Puryear R, Powers M, Cheng T, Ludwig EH, Sharma AM, Hata A, Jeunemaitre X, Lalouel JM. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J. Clin. Invest. 1997 Apr 4/1/1997; 99(7): 1786-97. PMID: 9120024, PMCID: PMC508000, DOI: 10.1172/JCI119343, ISSN: 0021-9738.

Williams CS, Luongo C, Radhika A, Zhang T, Lamps LW, Nanney LB, Beauchamp RD, DuBois RN. Elevated cyclooxygenase-2 levels in Min mouse adenomas. Gastroenterology. 1996 Oct; 111(4): 1134-40. PMID: 8831610, PII: S0016-5085(96)70083-5, ISSN: 0016-5085.

DuBois RN, Eberhart CF, Williams CS. Introduction to eicosanoids and the gastroenteric tract. Gastroenterol. Clin. North Am. 1996 Jun; 25(2): 267-77. PMID: 9229572, ISSN: 0889-8553.

Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms?. Am. J. Physiol. 1996 Mar; 270(3 Pt 1): G393-400. PMID: 8638704, ISSN: 0002-9513.

Hunt SC, Williams CS, Sharma AM, Inoue I, Williams RR, Lalouel JM. Lack of linkage between the endothelial nitric oxide synthase gene and hypertension. J Hum Hypertens. 1996 Jan; 10(1): 27-30. PMID: 8642187, ISSN: 0950-9240.

Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992 Oct 10/2/1992; 71(1): 169-80. PMID: 1394429, PII: 0092-8674(92)90275-H, ISSN: 0092-8674.

Available Postdoctoral Position Details
Postdoctoral position available to study intestinal inflammation, carcinogenesis, and deveopment. Expertise in molecular biology, animal models of disease, and biochemistry is highly desirable.