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Lee A. Denson, MD Medical Director, Inflammatory Bowel Disease Center
Medical Director, Inflammatory Bowel Disease Center
Professor, UC Department of Pediatrics
Inflammatory bowel disease; growth failure; celiac disease
Visit the Denson Lab.
The primary focus of Dr. Lee A. Denson's laboratory is to determine the molecular basis for alterations in growth hormone signaling in inflammatory bowel diseases (IBD).
Normal growth and development are dependent upon the ability of growth hormone to regulate IGF-1 expression. Evidence from studies in children with IBD and mouse models of colitis indicates that inflammatory cytokines which are up regulated in this setting may cause an acquired GH resistance. Consequences may include growth failure, altered body composition and impaired mucosal healing.
We are using complementary experimental and patient-based approaches to investigate regulation of growth hormone signaling in mouse models of colitis and in children with Crohn's disease. These include down regulation of the growth hormone receptor and up regulation of a family of post-receptor inhibitory proteins, the Suppressors of Cytokine Signaling (SOCS). These studies should lead to the development of more effective therapies for children with IBD and other chronic inflammatory conditions.
Herzer M, Denson LA, Baldassano RN, Hommel KA. Family functioning and health-related quality of life in adolescents with pediatric inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011 Jan;23(1):95-100.
Gray WN, Denson LA, Baldassano RN, Hommel KA. Disease activity, behavioral dysfunction, and health-related quality of life in adolescents with inflammatory bowel disease. Inflamm Bowel Dis. 2010 Nov 4.
Lawal TA, Frischer JS, Falcone RA, Chatoorgoon K, Denson LA, Levitt MA. The transanal approach with laparoscopy or laparotomy for the treatment of rectal strictures in Crohn's disease. J Laparoendosc Adv Surg Tech A. 2010 Nov;20(9):791-5.
Denson LA, Kim MO, Bezold R, Carey R, Osuntokun B, Nylund C, Willson T, Bonkowski E, Li D, Ballard E, Collins M, Moyer MS, Klein DJ. A randomized controlled trial of growth hormone in active pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2010 Aug;51(2):130-9.
Nylund CM, Denson LA, Noel JM. Bacterial enteritis as a risk factor for childhood intussusception: a retrospective cohort study. J Pediatr. 2010 May;156(5):761-5.
Ingerski LM, Baldassano RN, Denson LA, Hommel KA. Barriers to oral medication adherence for adolescents with inflammatory bowel disease. J Pediatr Psychol. 2010 Jul;35(6):683-91.
Tomer G, Wetzler G, Keddache M, Denson LA. Polymorphisms in the IBD5 locus are associated with Crohn disease in pediatric Ashkenazi Jewish patients. J Pediatr Gastroenterol Nutr. 2009 May;48(5):531-7.
Uchida K, Nakata K, Suzuki T, Luisetti M, Watanabe M, Koch DE, Stevens CA, Beck DC, Denson LA, Carey BC, Keicho N, Krischer JP, Yamada Y, Trapnell BC. Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects. Blood. 2009 Mar 12;113(11):2547-56.
Han X, Uchida K, Jurickova I, Koch D, Willson T, Samson C, Bonkowski E, Trauernicht A, Kim MO, Tomer G, Dubinsky M, Plevy S, Kugathsan S, Trapnell BC, Denson LA. Granulocyte-macrophage colony-stimulating factor autoantibodies in murine ileitis and progressive ileal Crohn's disease. Gastroenterology. 2009 Apr;136(4):1261-71, e1-3.
Denson LA. Growth hormone therapy in children and adolescents: pharmacokinetic/pharmacodynamic considerations and emerging indications. Expert Opin Drug Metab Toxicol. 2008 Dec;4(12):1569-80. Review.
Mike A. Leonis, MD, PhD
Assistant Professor, UC Department of Pediatrics
Pediatric hepatology, especially acute liver failure; inflammatory disease processes of the liver; hepatoblastoma; mechanisms of hepatic tumor formation
Stuart WD, Kulkarni RM, Gray JK, Vasiliauskas J, Leonis MA, Waltz SE. Ron receptor regulates Kupffer cell-dependent cytokine production and hepatocyte survival following endotoxin exposure in mice. Hepatology. 2011 May;53(5):1618-28.
Kenny AP, Crimmins NA, Mackay DJ, Hopkin RJ, Bove KE, Leonis MA. Concurrent course of transient neonatal diabetes with cholestasis and paucity of interlobular bile ducts: a case report. Pediatr Dev Pathol. 2009 Sep-Oct;12(5):417-20.
Leonis MA, Balistreri WF. Evaluation and management of end-stage liver disease in children. Gastroenterology. 2008 May;134(6):1741-51.
Caldwell CC, Martignoni A, Leonis MA, Ondiveeran HK, Fox-Robichaud AE, Waltz SE. Ron receptor tyrosine kinase-dependent hepatic neutrophil recruitment and survival benefit in a murine model of bacterial peritonitis. Crit Care Med. 2008 May;36(5):1585-93.
Leonis MA, Thobe MN, Waltz SE. Ron-receptor tyrosine kinase in tumorigenesis and metastasis. Future Oncol. 2007 Aug;3(4):441-8. Review.
Zinser GM, Leonis MA, Toney K, Pathrose P, Thobe M, Kader SA, Peace BE, Beauman SR, Collins MH, Waltz SE. Mammary-specific Ron receptor overexpression induces highly metastatic mammary tumors associated with beta-catenin activation. Cancer Res. 2006 Dec 15;66(24):11967-74.
Wetzel CC, Leonis MA, Dent A, Olson MA, Longmeier AM, Ney PA, Boivin GP, Kader SA, Caldwell CC, Degen SJ, Waltz SE. Short-form Ron receptor is required for normal IFN-gamma production in concanavalin A-induced acute liver injury. Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G253-61.
Leonis MA, Toney-Earley K, Degen SJ, Waltz SE. Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure. Hepatology. 2002 Nov;36(5):1053-60.
Scott P. Pentiuk, MD Pediatric Gastroenterologist
Feeding disorders, medical education
MD: University of Cincinnati College of Medicine, Cincinnati, Ohio, 2002.
Residency: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 2005.
Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 2008.
Boamah LM, Bohren JR, Pentiuk S, Baker R, Yi M, Moyer MS. Development and testing of a CD-ROM program for improving adolescent knowledge of inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2010 May;50(5):521-5.
Pentiuk S, Putnam PE, Collins MH, Rothenberg ME. Dissociation between symptoms and histological severity in pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):152-60.
Pentiuk SP, Miller CK, Kaul A. Eosinophilic esophagitis in infants and toddlers. Dysphagia. 2007 Jan;22(1):44-8. Epub 2006 Oct 6.
Noah F. Shroyer, PhD
Intestinal epithelial development; colon cancer; inflammatory bowel disease.
Visit the Shroyer Lab.
BS: Microbiology and Biochemistry, Louisiana State University, Baton Rouge, LA, 1995.
PhD: Cell and Molecular Biology, Baylor College of Medicine, Houston, TX, 2001.
Postdoctoral: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 2001-2005.
Spence JR, Lauf R, Shroyer NF. Vertebrate intestinal endoderm development. Dev Dyn. 2011 Mar;240(3):501-20.
Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature. 2011 Feb 3;470(7332):105-9.
Kazanjian A, Noah T, Brown D, Burkart J, Shroyer NF. Atonal homolog 1 is required for growth and differentiation effects of notch/gamma-secretase inhibitors on normal and cancerous intestinal epithelial cells. Gastroenterology. 2010 Sep;139(3):918-28, 928.e1-6.
Kohli R, Kirby M, Setchell KD, Jha P, Klustaitis K, Woollett LA, Pfluger PT, Balistreri WF, Tso P, Jandacek RJ, Woods SC, Heubi JE, Tschoep MH, D'Alessio DA, Shroyer NF, Seeley RJ. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G652-60. Phelan JD, Shroyer NF, Cook T, Gebelein B, Grimes HL. Gfi1-cells and circuits: unraveling transcriptional networks of development and disease. Curr Opin Hematol. 2010 Jul;17(4):300-7.
Noah TK,Kazanjian A, Whitsett J, Shroyer NF. SAM Pointed Domain ETS Factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells. Exp Cell Res. 2010 Feb;316(3):452-65.
Bossuyt W, Kazanjian A, Aerts S, Leenaerts I, Claeys A, de Geest N, van Kelst S, de Hertogh G, Geboes K, Chuah M, Boivin GP, VandenDriessche T, Marynen P, Cools J, Shroyer NF, Hassan BA. Atonal homolog 1 (Atoh1) is a tumor suppressor gene. PLoS Biology. 2009;7:e39. Kiesslich R, Goetz M, Angus EM, Hu Q, Guan Y, Potten C, Allen T, Neurath MF, Shroyer NF, Montrose MH, Watson AJM. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy: A translational study from mouse to man. Gastroenterology. 2007;133:1769-78.
Shroyer NF, Helmrath MA, Wang VY-C, Antalffy BA, Henning SJ, Zoghbi HY. Intestine specific ablation of Mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology. 2007; 132:2478-88.
Shroyer NF, Wallis Shultz D, Venken KJT, Bellen HJ, Zoghbi HY. Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation. Genes and Development. 2005;19:2412-7.
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