Biomedical Research Education & Training
Faculty Member

Williams, Christopher Shawn, M.D., Ph.D.
Associate Professor of Medicine
Associate Professor of Cancer Biology

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Phone Number: 615-322-3642

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Williams, Christopher's picture
Academic history
B.Sc., Brigham Young University
Ph.D., Vanderbilt
M.D., Vanderbilt
Medicine Residency, Vanderbilt
Gastorenterology Fellowship, Vanderbilt

Office Address   Mailing Address

1065-D Medical Research Building IV

Gastroenterology Division - 1030-C Medical Research Building IV - 37232-0252

Research Keywords
Transcriptional Regulation Intestinal Development Colorectal Cancer Inflammatory Bowel Disease Epigenetic Regulation,Apoptosis,Cancer,Chromatin,Gene regulation,Immunology,Knockout,Malignancy,Molecular medicine,Mouse,Mutation,Signal transduction,Stem cells,Transcription,Transformation

Clinical Research Keywords
Inflammatory Bowel Disease Inflammational Carcinogenesis

Research Specialty
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).

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:

1) Epigenetic control of intestinal epithelial wound healing and repair programs and relationship to colorectal oncogenesis.
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.

2) Junctional signaling in mucosal wound healing responses and inflammatory carcinogenesis.
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 Bves-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.

3) Oxidative injury defenses in Inflammatory Bowel Disease (IBD) and colitis associated carcinoma (CAC).
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.

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, 125(7), 2646-60, 2015

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, 29(3), 786-95, 2015

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, 308(6), G562-71, 2015

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, 36(7), 710-8, 2015

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, 73(3), 1245-55, 2013

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, 8(7), e67845, 2013

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, 8(12), e82300, 2013

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, 190(4), 1849-58, 2013

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, 305(3), G225-40, 2013

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, 7(12), e51205, 2012

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, 7(3), e33546, 2012 PMCID:3299802

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, 2012

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, 71(4), 1302-12, 2011

Russ, PK, Pino, CJ, Williams, CS, Bader, DM, Haselton, FR, Chang, MS. Bves modulates tight junction associated signaling. PLoS One, 6(1), e14563, 2011 PMCID:3024319

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, 121(10), 4056-69, 2011 PMCID:3195453

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, 16(9), 1557-66, 2010 PMCID:2894261

Whittem, CG, Williams, AD, Williams, CS. Murine Colitis modeling using Dextran Sulfate Sodium (DSS). J Vis Exp(35), 2010 PMCID:2894261

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, 104(6), 2228-40, 2008

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 TCFs and Influence TCF-Dependent Transcription. Mol Cell Biol, 2007 PMCID:2223385

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, 131(2), 579-88, 2006

Smith, DS, Williams, CS, Ferris, CD. Diagnosis and treatment of chronic gastroparesis and chronic intestinal pseudo-obstruction. Gastroenterol Clin North Am, 32(2), 619-58, 2003

Aklog, L, Williams, CS, Byrne, JG, Goldhaber, SZ. Acute pulmonary embolectomy: a contemporary approach. Circulation, 105(12), 1416-9, 2002

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, 120(7), 1713-9, 2001

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, 3(5), 428-36, 2001 PMCID:1506203

Callejas, NA, Bosc?!, L, Williams, CS, DuBOIS, RN, Mart?-n-Sanz, P. Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins. Gastroenterology, 119(2), 493-501, 2000

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, 275(9), 6628-35, 2000

Williams, CS, Tsujii, M, Reese, J, Dey, SK, DuBois, RN. Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest, 105(11), 1589-94, 2000 PMCID:300858

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, 60(21), 6045-51, 2000

Williams, CS, Goldman, AP, Sheng, H, Morrow, JD, DuBois, RN. Sulindac sulfide, but not sulindac sulfone, inhibits colorectal cancer growth. Neoplasia, 1(2), 170-6, 1999 PMCID:1508136

Williams, CS, Mann, M, DuBois, RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene, 18(55), 7908-16, 1999

Williams, CS, Shattuck-Brandt, RL, DuBois, RN. The role of COX-2 in intestinal cancer. Expert Opin Investig Drugs, 8(1), 1-12, 1999

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, 19(12), 2195-9, 1998

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, 19(4), 543-9, 1998

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, 273(34), 22120-7, 1998

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, 99(7), 1786-97, 1997 PMCID:508000

Williams, CS, Smalley, W, DuBois, RN. Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Invest, 100(6), 1325-9, 1997 PMCID:508309

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, 57(9), 1638-43, 1997

DuBois, RN, Eberhart, CF, Williams, CS. Introduction to eicosanoids and the gastroenteric tract. Gastroenterol Clin North Am, 25(2), 267-77, 1996

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, 10(1), 27-30, 1996

Williams, CS, DuBois, RN. Prostaglandin endoperoxide synthase: why two isoforms. Am J Physiol, 270(3 Pt 1), G393-400, 1996

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, 111(4), 1134-40, 1996

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, 71(1), 169-80, 1992

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