D. Brent Polk, MD, is chair of the Department of Pediatrics and Director of The Saban Research Institute. He is also chair of pediatrics and vice dean for Child Health at the Keck School of Medicine of the University of Southern California. A distinguished researcher and clinician, Dr. Polk serves as a professor of pediatrics at the Keck School of Medicine. As chair of pediatrics, he is responsible for the department’s educational, research and service missions, and oversees faculty working at Children’s Hospital and Los Angeles County+USC Medical Center.
Dr. Polk previously served as chief of the D. Brent Polk Division of Pediatric Gastroenterology, Hepatology and Nutrition, director of the Digestive Disease Research Center and a tenured professor of Pediatrics and Cell and Developmental Biology at Vanderbilt University Medical Center. He received a bachelor’s degree in biology and chemistry from Ouachita University in Arkadelphia, Ark., and his medical degree from the University of Arkansas for Medical Sciences.
University of Arkansas for Medical Sciences and Arkansas Childrens Hospital; Pediatrics
University of Arkansas for Medical Sciences and Arkansas Childrens Hospital; Pediatrics
Pediatric Gastroenterology; American Board of Pediatrics
American Gastroenterological Association; American Academy of Pediatrics (AAP); American Gastroenterological Association (AGA); American Pediatric Society (APS); American Physiological Society (APS); American Society for Biochemistry and Molecular Biology (ASBMB); American Society for Cell Biology (ASCB); American Society for Parenteral and Enteral Nutrition (ASPEN); Crohn's and Colitis Foundation of America (CCFA); Council of Delegates, Intestinal Disorders Section of AGA; Federation of American Societies for Experimental Biology (FASEB); Gastroenterology Research Group (GRG); North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN); Society for Pediatric Research (SPR).
Fellow, 2008; University of Arkansas College of Medicine, Distinguished Alumni Award, 2009; Grant W. Liddle Award, 2009
Yan F, Wang L, Shi Y, Cao H, Liu L, Washington MK, Chaturvedi R, Israel DA, Cao H, Wang B, Peek RM Jr, Wilson KT, Polk DB. Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice. Am J Physiol Gastrointest Liver Physiol. 2012 Mar;302(5):G504-14. Epub 2011 Dec 15. PubMed PMID: 22173918.
Zhang Y, Dubé PE, Washington MK, Yan F, Polk DB. ErbB2 and ErbB3 regulate recovery from dextran sulfate sodium-induced colitis by promoting mouse colon epithelial cell survival. Lab Invest. 2012 Mar;92(3):437-50. doi: 10.1038/labinvest.2011.192. Epub 2011 Dec 12. PubMed PMID: 22157714; PubMed Central PMCID: PMC3289719.
Weitkamp JH, Koyama T, Rock MT, Correa H, Goettel JA, Matta P, Oswald-Richter K, Rosen MJ, Engelhardt BG, Moore DJ, Polk DB. Necrotising enterocolitis is characterized by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratios. Gut. 2012 Jan 20. [Epub ahead of print] PubMed PMID: 22267598.
Yan F, Polk DB. Characterization of a probiotic-derived soluble protein which reveals a mechanism of preventive and treatment effects of probiotics on intestinal inflammatory diseases. Gut Microbes. 2012 Jan 1;3(1). [Epub ahead of print] PubMed PMID: 22356855.
Chaturvedi R, Asim M, Romero-Gallo J, Barry DP, Hoge S, de Sablet T, Delgado AG, Wroblewski LE, Piazuelo MB, Yan F, Israel DA, Casero RA Jr, Correa P, Gobert AP, Polk DB, Peek RM Jr, Wilson KT. Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA.Gastroenterology. 2011 Nov;141(5):1696-708.e1-2. Epub 2011 Aug 10. PubMed PMID: 21839041; PubMed Central PMCID: PMC3202654.
Ueno PM, Oriá RB, Maier EA, Guedes M, de Azevedo OG, Wu D, Willson T, Hogan SP, Lima AA, Guerrant RL, Polk DB, Denson LA, Moore SR. Alanyl-glutamine promotes intestinal epithelial cell homeostasis in vitro and in a murine model of weanling undernutrition. Am J Physiol Gastrointest Liver Physiol. 2011 Oct;301(4):G612-22. doi: 10.1152/ajpgi.00531.2010. Epub 2011 Jul 28. PubMed PMID: 21799183; PubMed Central PMCID: PMC3191556.
Yan F, Polk DB. Probiotics and immune health. Curr Opin Gastroenterol. 2011 Oct;27(6):496-501. Review. PubMed PMID: 21897224.
Hilliard VC, Frey MR, Dempsey PJ, Peek RM Jr, Polk DB. TNF-α converting enzyme-mediated ErbB4 transactivation by TNF promotes colonic epithelial cell survival. Am J Physiol Gastrointest Liver Physiol.2011 Aug;301(2):G338-46. Epub 2011 May 26. PubMed PMID: 21617117; PubMed Central PMCID: PMC3154600.
Yamaoka T, Frey MR, Dise RS, Bernard JK, Polk DB. Specific epidermal growth factor receptor autophosphorylation sites promote mouse colon epithelial cell chemotaxis and restitution. Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G368-76. Epub 2011 May 26. PubMed PMID: 21617115; PubMed Central PMCID: PMC3154598.
Hobbs SS, Goettel JA, Liang D, Yan F, Edelblum KL, Frey MR, Mullane MT, Polk DB. TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G220-9. Epub 2011 May 12. PubMed PMID: 21566012; PubMed Central PMCID: PMC3154604.
McElroy SJ, Prince LS, Weitkamp JH, Reese J, Slaughter JC, Polk DB. Tumor necrosis factor receptor 1-dependent depletion of mucus in immature small intestine: a potential role in neonatal necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol. 2011 Oct;301(4):G656-66. doi: 10.1152/ajpgi.00550.2010. Epub 2011 Jul 7. PubMed PMID: 21737776; PubMed Central PMCID: PMC3191555.
Yan F, Cao H, Cover TL, Washington MK, Shi Y, Liu L, Chaturvedi R, Peek RM Jr, Wilson KT, Polk DB. Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism. J Clin Invest. 2011 Jun;121(6):2242-53. doi: 10.1172/JCI44031. Epub 2011 May 23. PubMed PMID: 21606592; PubMed Central PMCID: PMC3104743.
Rosen MJ, Frey MR, Washington MK, Chaturvedi R, Kuhnhein LA, Matta P, Revetta FL, Wilson KT, Polk DB. STAT6 activation in ulcerative colitis: a new target for prevention of IL-13-induced colon epithelial cell dysfunction. Inflamm Bowel Dis. 2011 Nov;17(11):2224-34. doi: 10.1002/ibd.21628. Epub 2011 Feb 9. PubMed PMID: 21308881; PubMed Central PMCID: PMC3120916.
Regulation of the growth and development of the intestine
Childhood inflammatory bowel disease
Our laboratory studies the regulation of the growth and development of the intestine as it relates to injury, inflammation, regeneration and associated cancer. Our ultimate goal is to identify novel ways to better treat or possibly prevent childhood inflammatory bowel disease.
Our current areas of investigation include epidermal growth factor and tumor necrosis factor receptor signaling mechanisms leading to cellular growth, survival, development, wound healing and how these factors influence inflammation and cancer.
We have identified how these signaling systems contribute to disease in colitis models and how they influence long-term cancer risk, which is a major concern for pediatric patients with inflammatory bowel disease.
Our goal is to better understand how to treat or prevent intestinal inflammation, injury and cancer.
We have also identified one of the only known mechanisms through which probiotic bacteria can protect the colon from injury and inflammation.
We use cutting-edge techniques to study these questions, including in vivo models, novel genetic approaches, cell culture systems, state-of-the-art microscopy and colonoscopy imaging systems.
Key Findings and Achievements
- Determined the mechanisms controlling EGFR and TNFR1/2 signaling in colon epithelial cells.
- Determined the roles of ErbB2 and ErbB3 in colitis.
- Determined how the signaling molecule KSR regulates colon epithelial cell survival.
- Identified and determined how a protein produced by probiotic bacteria protects colon epithelial cells and treats colitis.
My laboratory is focused on the regulation of growth and development of the intestinal cell as it relates to growth, development and disease. Current areas of investigation include epidermal growth factor and tumor necrosis factor receptor family member signaling mechanisms leading to proliferation, differentiation, survival or migration of intestinal cells and the relationship between inflammation and tumorigenesis.
- NIH R01DK056008: Cytokine regulation of intestinal epithelial restitution
These studies are designed to test the hypothesis that during acute injury and chronic inflammation TNF stimulates TNFR processing and signal transduction, including transactivation of EGFR/ErbB2, to promote epithelial cell monolayer integrity and health of the host. The overall goal of these studies is to better understand the role of TNFR signaling during intestinal epithelial injury repair responses and inflammation.
- NIH R01DK066176: Mechanism of KSR regulation of intestinal cell survival
The goal of this proposal is to test our hypothesis that KSR kinase activity regulates IEC survival during the inflammatory response through activation of anti-apoptotic signal transduction pathways. Aim 1 is designed to determine the mechanisms regulating KSR activation. The focus of Aim 2 is to identify substrates and downstream targets of KSR in IECs. In Aim 3 we will study the biological role of KSR in intestinal epithelial injury using in vivo models.
- NIH P01CA116087: H.pylori-induced inflammation and gastric cancer
The overarching objective of Project 2 is delineation of the EGFR molecular signaling events initiated by H. pylori epithelial cell contact that regulate phenotypes related to gastric carcinogenesis.
- Welcome Trust: The Role of NF-kB and Cell Shedding in Inflammatory Bowel Disease
The goal of this proposal is to use models of IBD to identify molecular pathways that regulate gastrointestinal epithelial barrier function and bacterial translocation in chronic intestinal inflammation, with emphasis on the TNF and NF- kappaB signaling pathways.