Denson Lab Overview
The primary focus of Dr. Lee Denson's laboratory at Cincinnati Children's Hospital Medical Center 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. Recent data also indicate that GH may nevertheless exert an anti-inflammatory effect in colitis.
We are currently investigating potential mechanisms of cytokine dependent growth hormone resistance 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). We have also begun to characterize the manner in which GH may directly reduce chronic inflammation and promote mucosal healing. Currently Dr. Denson is the principal investigator on a randomized clinical trial which will determine whether the addition of growth hormone to standard therapy will promote mucosal healing and catch up growth in children with Chrohn's disease. These studies should lead to the development of more effective therapies for children with IBD and other chronic inflammatory conditions.
Publications
- Denson,L., E. Sturm, W. Echevarria, T. Zimmerman, M. Makishima, D. Mangelsdorf, and S. Karpen. The orphan nuclear receptor, shp, mediates bile acid induced inhibition of the rat bile acid transporter, ntcp. 2001 Gastroenterology, 121:140-7.
- Denson, L., R. Menon , A. Shaufl, H. Bajwa, C. Williams, and S. Karpen. Tumor necrosis factor alpha down regulates murine hepatic growth hormone receptor gene expression via inhibition of Sp1 and Sp3 binding. 2001 Journal of Clinical Investigation, 107:1451-8..
- Spirli, C., M. Nathanson, R. Fiorotto, E. Duner, L. Denson, C. Valvason, J. Sanz, F. Virgilio, F. Casagrande, and M. Strazzabosco. Pro-inflammatory cytokines inhibit secretion in rat bile duct epithelium. 2001 Gastroenterology, 121:156-69.
- Denson, L., A Bohan, M. Held, and J. Boyer. Alterations in RAR:RXR nuclear receptor abundance regulate rat Mrp2 (Abcc2) expression in obstructive cholestasis. 2002 Gastroenterology, 123:599-607.
- Denson L. Regulation of growth hormone signaling by inflammatory cytokines. 2002 Recent Research Developments in Biological Chemistry, 1:333-355.
- Denson, L. Alpha-one antitrypsin deficiency. Mosby's Pediatric Clinical Advisor. Mosby, 2002
- Denson, L., M. Held, R. Menon, S. Frank, A. Parlow, and D. Arnold. Interleukin 6 inhibits hepatic growth hormone signaling via induction of cis and socs-3. 2003 Am J Physiol Gastrointest Liver Physiol, 284:G646-G654.
- Bohan, A., W. Chen, L. Denson, M. Held, and J. Boyer. TNF alpha dependent up-regulation of Lrh-1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis. 2003 J. Biol. Chem. 278:36688-98.
- Puppin, C., A. D'Élia, L. Pellizzari, D. Russo, F. Arturi, I. Presta, S. Filetti, C. Bogue, L. Denson, and G. Damante. Thyroid-specific transcription factors control Hex promoter activity. 2003 Nucleic Acids Research, 31:1845-1852.
- Denson, L. Postnatal Infections of the Liver: Viral – Other. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management – 4th Edition. BC Decker. 2003
Held, MA., W. Cosme-Blanco, LM. DiFedele, EL. Bonkowski, RK. Menon, and LA. Denson. Alterations in growth hormone receptor abundance regulate growth hormone signaling in murine obstructive cholestasis. 2005. Am J Physiol Gastrointest Liver Physiol, 288:G986-G993.
DiFedele, LM., J. He, EL. Bonkowski, X. Han, MA. Held, A. Bohan, RK. Menon, and LA. Denson. Tumor necrosis factor alpha blockade restores growth hormone signaling in murine colitis. 2005. Gastroenterology, 128:1278-91.
Han, X., D. Sosnowska, EL. Bonkowski, and LA. Denson. Growth hormone inhibits signal transducer and activator of transcription 3 activation and reduces disease activity in murine colitis. 2005. Gastroenterology, 129:185-203.
Contact Us
Lee A. Denson, MD
Associate Professor, Pediatrics
Division of Gastroenterology, Hepatology, and Nutrition
Cincinnati Children's Hospital Medical Center
MLC 2010
3333 Burnet Avenue
Cincinnati, OH 45229-3039
Email lee.denson@cchmc.org
Phone 513-636-7575
fax 513-636-5581
