Center for Matrix Biology - Vanderbilt University and Medical Center

D. Brent Polk, M.D.
Professor in the Department of Pediatrics

	Office Address:	1025 MRBIV
	Mailing Address:	2215 Garland Avenue 1025 MRBIV Nashville, TN 37232-0696
	Lab address:	1025 MRBIV
	Phone:	(615) 322-7449
		email \| website

Secondary appointment in the Cell and Developmental Biology department.

Research Summary

My laboratory is focused on the regulation of growth and development of the intestinal cell as it relates to ontogeny and disease. Current areas of investigation include epidermal growth factor and tumor necrosis factor receptor family member signaling mechanisms leading to proliferation, differentiation or migration of intestinal cells and the relationship between inflammation and tumorigenesis. These findings have been extended to understanding the relationship between commensal and pathogenic enteric bacterial flora and regulation of intestinal cell proliferation and apoptosis.

Research Keywords

Apoptosis, Biochemistry, Developmental biology, Microbiology, Mouse, Physiology, Receptor, Signal transduction,

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Associated initiative(s):

Wound Repair

Career opportunities:
Postdoctoral Position Available

Selected Publications

» Frey MR, Mullane ML, Hilliard VC and Polk DB. ErbB4 promotes cyclooxygenase-2 expression and cellular transformation in colon epithelial cells. . :

» Hobbs SS, Krishna U, Ogden S, Peek Jr RM and Polk DB. Transactivation of EGFR by Cag+ H. pylori infection regulates COX-2 expression and gastric epithelial cell survival. . :

» Hobbs SS, Yamaoka T, Goettel JA, Liang D and Polk DB. Tumor necrosis factor-mediated EGFR transactivation promotes COX-2 expression and survival in colon epithelial cells. 2009. :

» Sheng H, Shao J, Morrow JD, Yan F, Polk DB, Dubois RN. A selective cyclooxygenase-2 inhibitor increases mortaility in IL-10-/- mice. 2009. :

» Frey MR, Edelblum KL, Liang D and Polk DB The ErbB4 growth factor receptor is required for mouse colon epithelial cell survival in the presence of TNF Gastroenterology 2009. 136:217-226

» Yan F, Cao H, Chaturvedi R, Krishna U, Hobbs SS, Dempsey PJ, Peek Jr RM, Cover TL, Washington MK, Wilson KT and Polk DB Epidermal growth factor receptor activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis Gastroenterology 2009. 136:1297-1307.e3

» Weitkamp JH, Rudzinski E, Koyama T, Correa H, Alberty B and Polk DB. Ontogeny of FOXP3+ Regulatory T Cells in the Postnatal Human Small Intestinal and Large Intestinal Lamina Propria Pediatric and Developmental Pathology 2009. :

» Li B, Pagni M, Brantley-Sieders D, Cates J, Polk DB and Young PP. Low levels of TNFα increase tumor growth by inducing an endothelial phenotype of monocytes recruited to the tumor site. Cancer Research 2009. :

» Edelblum KL, Goettel JA, Koyama T, McElroy SJ, Yan F and Polk DB TNFR1 promotes TNF-mediated mouse colon epithelial cell survival through Raf activation of NF-kB Journal of Biological Chemistry 2008. 283:29485-29494

» Yamaoka T,Yan F, Cao H, Hobbs SS, Tong W, Dise RS and Polk DB Transactivation of epidermal growth factor receptor and ErbB2 protects intestinal epithelial cells from tumor necrosis factor-induced apoptosis Proceedings of National Academy of Sciences (Track 2) 2008. :11772-7

» Edelblum KL, Washington MK, Koyama T, Robine S, Baccarini M and Polk DB. Raf protects against colitis by promoting mouse colon epithelial cell survival through NF-kB. Gastroenterology 2008. 135:539-51

» Seth A, Yan F, Polk DB and Rao RK. Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC and MAP kinase-dependent mechanism. American Journal of Physiology: Gastroenterology and Liver Physiology 2008. :G1060-9

» McElroy SJ, Frey MR, Yan F, Edelblum KL, Goettel JA, John S, and Polk DB Tumor necrosis factor inhibits ligand-stimulated EGF receptor activation through a TNF receptor 1-dependent mechanism. American Journal of Physiology: Gastroenterology and Liver Physiology 2008. :G285-93

» Vanderpool C, Yan F and Polk DB. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases. Inflammatory Bowel Disease Journal 2008. 14:1585-96

» Yan, F, Cao, H, Cover, TL, Whitehead, R, Washington, MK, Polk, DB Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth Gastroenterology 2007. 132:562-75

» Chen, X, Abair, TD, Ibanez, MR, Su, Y, Frey, MR, Dise, RS, Polk, DB, Singh, AB, Harris, RC, Zent, R, Pozzi, A Integrin alpha1beta1 controls reactive oxygen species synthesis by negatively regulating epidermal growth factor receptor-mediated Rac activation Mol Cell Biol 2007. 27:3313-26

» Dise, RS, Frey, MR, Whitehead, RH, Polk, DB EPIDERMAL GROWTH FACTOR STIMULATES RAC ACTIVATION THROUGH SRC AND PHOSPHATIDYLINOSITOL 3-KINASE TO PROMOTE COLONIC EPITHELIAL CELL MIGRATION Am J Physiol Gastrointest Liver Physiol 2007. :

» Batts, LE, Polk, DB, Dubois, RN, Kulessa, H Bmp signaling is required for intestinal growth and morphogenesis Dev Dyn 2006. :

» Frey, MR, Dise, RS, Edelblum, KL, Polk, DB p38 kinase regulates epidermal growth factor receptor downregulation and cellular migration EMBO J 2006. 25:5683-92

» Yan, F, Polk, DB Probiotics as functional food in the treatment of diarrhea Curr Opin Clin Nutr Metab Care 2006. 9:717-21

» O'Brien, DP, Israel, DA, Krishna, U, Romero-Gallo, J, Nedrud, J, Medof, ME, Lin, F, Redline, R, Lublin, DM, Nowicki, BJ, Franco, AT, Ogden, S, Williams, AD, Polk, DB, Peek, RM The role of decay-accelerating factor as a receptor for Helicobacter pylori and a mediator of gastric inflammation J Biol Chem 2006. :

» Edelblum, KL, Yan, F, Yamaoka, T, Polk, DB Regulation of apoptosis during homeostasis and disease in the intestinal epithelium Inflamm Bowel Dis 2006. 12:413-24

» Yan F, John Sutha K, Wilson Guinn, Jones David S, Washington K and Polk DB Kinase suppressor of Ras protects intestinal epithelium from cytokine-mediated apoptosis during inflammation Journal of Clinical Investigation 2004. 114:1272-1280

» Yan Fang and Polk, D. Brent Commensal bacteria in the gut: learning who our friends are Current Opinion in Gastroenterology 2004. 20:565-571

» Walker LS, Lipani TA, Greene JW, Caines K, Stutts J, Polk DB, Caplan A, and Rasquin-Weber A Recurrent Abdominal Pain: Recurrent Abdominal Pain: Subtypes based on the Rome II Criteria for Pediatric Functional Gastrointestinal Disorders. Journal of Pediatric Gastroenterology and Nutrition 2004. 38:187-191

» Frey Mark, Golovin Anasatsia and Polk D. Brent Polk EGF-stimulated intestinal epithelial cell migration requires Src-dependent activation of p38 Journal of Biological Chemistry 2004. 279:44513

» Profeta A, Greene J, Polk DB and Walker L Agreement between clinical judgement and the Pediatric Rome Criteria for irritable bowel syndrome in children Journal of Pediatric Gastroenterology and Nutrition 2004. :

» Walker, LS, Lipani, TA, Greene, JW, Caines, K, Stutts, J, Polk, DB, Caplan, A, Rasquin-Weber, A Recurrent abdominal pain: symptom subtypes based on the Rome II Criteria for pediatric functional gastrointestinal disorders J Pediatr Gastroenterol Nutr 2004. 38:187-91

» Yan, F, John, SK, Wilson, G, Jones, DS, Washington, MK, Polk, DB Kinase suppressor of Ras-1 protects intestinal epithelium from cytokine-mediated apoptosis during inflammation J Clin Invest 2004. 114:1272-80

» Yan, F, Polk, DB Commensal bacteria in the gut: learning who our friends are Curr Opin Gastroenterol 2004. 20:565-71

» Corredor, Julissa, Yan, Fang, Shen, Christopher C, Tong, Wei, John, Sutha K, Wilson, Guinn, Whitehead, Robert, Polk, D Brent Tumor necrosis factor regulates intestinal epithelial cell migration by receptor-dependent mechanisms Am J Physiol Cell Physiol 2003. 284:C953-61

» Washington, Kay, Greenson, Joel K, Montgomery, Elizabeth, Shyr, Yu, Crissinger, Karen D, Polk, D Brent, Barnard, John, Lauwers, Gregory Y Histopathology of ulcerative colitis in initial rectal biopsy in children Am J Surg Pathol 2002. 26:1441-9

» Yan F, Polk DB Prevention of cytokine-induced intestinal epithelial cell apoptosis by probiotic bacterium Journal of Biological Chemistry 2002. 277:50959-50965

» Montgomery, Robert, Ghishan, Fayez K, Moyer, Mary Susan, Polk, D Brent, Thompson, John F Research agenda for pediatric gastroenterology, hepatology and nutrition: developmental physiology and pathophysiology. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation J Pediatr Gastroenterol Nutr 2002. 35 Suppl 3:S242-5

» Yan, Fang, Polk, D Brent Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells J Biol Chem 2002. 277:50959-65

» Hernanz-Schulman, M, Lowe, L H, Johnson, J, Neblett, W W, Polk, D B, Perez, R, Scheker, L E, Stein, S M, Heller, R M, Cywes, R In vivo visualization of pyloric mucosal hypertrophy in infants with hypertrophic pyloric stenosis: is there an etiologic role? AJR Am J Roentgenol 2001. 177:843-8

» Yan, F, John, S K, Polk, D B Kinase suppressor of Ras determines survival of intestinal epithelial cells exposed to tumor necrosis factor Cancer Res 2001. 61:8668-75

» Yan, F, Polk, D B Kinase suppressor of ras is necessary for tumor necrosis factor alpha activation of extracellular signal-regulated kinase/mitogen-activated protein kinase in intestinal epithelial cells Cancer Res 2001. 61:963-9

» Gupta, R A, Polk, D B, Krishna, U, Israel, D A, Yan, F, DuBois, R N, Peek, R M Activation of peroxisome proliferator-activated receptor gamma suppresses nuclear factor kappa B-mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells J Biol Chem 2001. 276:31059-66

» Kaiser, G C, Yan, F, Polk, D B Mesalamine blocks tumor necrosis factor growth inhibition and nuclear factor kappaB activation in mouse colonocytes Gastroenterology 1999. 116:602-9

» Polk, D B, Tong, W Epidermal and hepatocyte growth factors stimulate chemotaxis in an intestinal epithelial cell line Am J Physiol 1999. 277:C1149-59

» Yan, F, Polk, D B Aminosalicylic acid inhibits IkappaB kinase alpha phosphorylation of IkappaBalpha in mouse intestinal epithelial cells J Biol Chem 1999. 274:36631-6

» Kaiser, G C, Yan, F, Polk, D B Conversion of TNF alpha from antiproliferative to proliferative ligand in mouse intestinal epithelial cells by regulating mitogen-activated protein kinase Exp Cell Res 1999. 249:349-58

» Polk, D B Epidermal growth factor receptor-stimulated intestinal epithelial cell migration requires phospholipase C activity Gastroenterology 1998. 114:493-502

» Hernanz-Schulman, M, Neblett, W W, Polk, D B, Johnson, J E Hypertrophied pyloric mucosa in patients with hypertrophic pyloric stenosis Pediatr Radiol 1998. 28:901

» Kaiser, G C, Polk, D B Tumor necrosis factor alpha regulates proliferation in a mouse intestinal cell line Gastroenterology 1997. 112:1231-40

» Taufiq, S, Hernanz-Schulman, M, Wheeler, A V, Morgan, W M, Teague, M D, Polk, D B Recurrent necrotizing jejunitis in a child J Pediatr 1996. 128:246-9

» Polk, D B Shc is a substrate of the rat intestinal epidermal growth factor receptor tyrosine kinase Gastroenterology 1995. 109:1845-51

» Molrine, D C, Polk, D B, Ciamarra, A, Phillips, N, Ambrosino, D M Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes Infect Immun 1995. 63:2867-72

» Hernanz-Schulman, M, Dinauer, P, Ambrosino, M M, Polk, D B, Neblett, W W The antral nipple sign of pyloric mucosal prolapse: endoscopic correlation of a new sonographic observation in patients with pyloric stenosis J Ultrasound Med 1995. 14:283-7

» Polk, D B, McCollum, G W, Carpenter, G Cell density-dependent regulation of PLC gamma 1 tyrosine phosphorylation and catalytic activity in an intestinal cell line (IEC-6) J Cell Physiol 1995. 162:427-33

» Polk, D B Ontogenic regulation of phospholipase C-gamma 1 activity and expression in the rat small intestine Gastroenterology 1994. 107:109-16

» Sacks, A I, Acra, S A, Dykes, W, Polk, D B, Barnard, J A, Pietsch, J, Ghishan, F K Intestinal Na+/H+ exchanger activity is up-regulated by bowel resection in the weanling rat Pediatr Res 1993. 33:215-20

» Polk, D B, Hattner, J A, Kerner, J A Improved growth and disease activity after intermittent administration of a defined formula diet in children with Crohn's disease JPEN J Parenter Enteral Nutr 1992. 16:499-504

» Polk, D B, Steele, R W Bacterial meningitis presenting with normal cerebrospinal fluid Pediatr Infect Dis J 1987. 6:1040-2