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Lee A. Denson, MD

Director, Schubert-Martin Inflammatory Bowel Disease Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7575

Email lee.denson@cchmc.org

Clinical & Research Interests
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Clinical

Inflammatory bowel disease; growth failure; celiac disease

Biography
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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.

Education and Training
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MD: Medical College of Virginia, Richmond, VA, 1993.

Residency: Yale-New Haven Hospital, New Haven, CT, 1993-96.

Certification: Pediatrics, 1996 and 2002.

Fellowship: Yale University School of Medicine, New Haven, CT, 1996-99.

Publications
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View PubMed Publications

Ning K, Gettler K, Zhang W, Ng SM, Bowen BM, Hyams J, Stephens MC, Kugathasan S, Denson LA, Schadt EE, Hoffman GE, Cho JH. Improved integrative framework combining association data with gene expression features to prioritize Crohn's disease genes. Hum Mol Genet. 2015 Jul 15;24(14):4147-57.

Minar P, Haberman Y, Jurickova I, Wen T, Rothenberg ME, Kim MO, Saeed SA, Baldassano RN, Stephens M, Markowitz J, Rosh J, Crandall WV, Heyman MB, Mack DR, Griffiths AM, Baker SS, Hyams JS, Kugathasan S, Denson LA. Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease. Inflamm Bowel Dis. 2014 Jun;20(6):1037-48.

Haberman Y, Tickle TL, Dexheimer PJ, Kim MO, Tang D, Karns R, Baldassano RN, Noe JD, Rosh J, Markowitz J, Heyman MB, Griffiths AM, Crandall WV, Mack DR, Baker SS, Huttenhower C, Keljo DJ, Hyams JS, Kugathasan S, Walters TD, Aronow B, Xavier RJ, Gevers D, Denson LA. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. J Clin Invest. 2014 Aug;124(8):3617-33.

Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, González A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, Heyman M, Markowitz J, Baldassano R, Griffiths A, Sylvester F, Mack D, Kim S, Crandall W, Hyams J, Huttenhower C, Knight R, Xavier RJ. The treatment-naïve microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014 Mar 12;15(3):382-92.

Dykes D, Towbin A, Bonkowski E, Chalk C, Bezold R, Lake K, Kim M, Heubi J, Trapnell B, Podberesky D, Denson L. Increased Prevalence of Luminal Narrowing and Stricturing by Enterography in Pediatric Crohn Disease Patients with Elevated Granulocyte-Macrophage Colony Stimulating Factor Auto-antibodies. Inflamm Bowel Dis. 2013 Sep;19(10):2146-54.

Jurickova I, Collins M, Chalk C, Seese A, Bezold R, Lake K, von Allmen D, Frischer J, Trapnell B, Denson L. Pediatric Crohn Disease Patients with Stricturing Behavior Exhibit Ileal Granulocyte-Macrophage Colony Stimulating Factor Auto-antibody Production and Reduced Neutrophil Bacterial Killing and GM-CSF Bioactivity. Clin Exp Immunol. 2013 Jun;172(3):455-65.

Samson CM, Jurickova I, Molden E, Schreiner W, Colliver J, Bonkowski E, Han X, Trapnell BC, Denson LA. Granulocyte-Macrophage Colony Stimulating Factor Blockade Promotes CCR9+ Lymphocyte Expansion in Nod2 Deficient Mice. Inflamm Bowel Dis. 2011 Dec;17(12):2443-55.

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. GM-CSF Auto-antibodies in Murine Ileitis and Progressive Ileal Crohn’s Disease. Gastroenterology. 2009 Apr;136(4):1261-71, e1-3. 

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.

Han X, Sosnowska D, Bonkowski E, Denson L. Growth hormone inhibits STAT3 activation and reduces disease activity in murine colitis. Gastroenterology. 2015;129:185-203.

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