The Role of TL1A/DR3 in Intestinal Inflammation

Fabio Cominelli, MD, PhD, is Professor of Medicine and Pathology, Chief of the Division of Gastroenterology and Liver Disease, and Director of the Digestive Health Research Institute at Case Western Reserve University (CWRU) and University Hospitals of Cleveland. He is also the inaugural awardee of the Hermann Menges Jr Chair in Internal Medicine and Associate Dean for Program Development. Dr. Cominelli is the Principal Investigator (PI) and Director of a National Institutes of Health (NIH) Program Project Grant, studying the role of innate immunity in experimental Crohn’s disease, and two R01 grants focused on the role of cytokines and commensal flora in the pathogenesis of intestinal inflammation. He is also the PI of a T32 Training grant in Digestive Disease Sciences at CWRU, as well as the PI and Director of the Cleveland NIH Digestive Diseases Research Core Center.
His research interest in the area of experimental inflammatory bowel disease and intestinal cytokines dates back 28 years to his fellowship in Gastroenterology research under Dr. Robert Zipser at Harbor UCLA Medical Center. These two general areas of research have remained the focus of his investigation ever since. In recognition of his research accomplishments, Dr. Cominelli was the recipient of the 2002 Outstanding Investigator Award from the American Federation for Medical Research for his studies establishing that targeted neutralization of a specific cytokine was effective for the treatment of experimental IBD. Dr. Cominelli has over 25 years of experience and continuous NIH funding in cytokine biology and many seminal discoveries in this field of investigation. His group was the first to report that specific blockade of a single pro-inflammatory cytokine, i.e. interleukin-1 (IL-1), was effective in reducing disease severity in an animal model of experimentally-induced colitis and that an imbalance between intestinal pro- and anti-inflammatory cytokines represents a pathogenic mechanism of auto-inflammatory diseases, including IBD. This concept has now gained considerable attention through reports of severe inflammatory disease in infants with homozygous germ-line mutations in the IL-1 gene family. These and other studies have formed the foundation for clinical trials using anti-cytokine therapy (e.g. anti-TNFα therapy) as well as administration of anti-inflammatory cytokines, (e.g. IL-1 receptor antagonist) in patients with auto-inflammatory diseases. Dr. Cominelli has published more than 150 articles and has extensive experience as a journal reviewer. He has been an Associate Editor and an Editorial Board Member for several Journals including the Journal of Immunology, Gastroenterology, Digestive and Liver Disease, The American Journal of Physiology and others. He is currently an Academic Editor for PLoS One and Associate Editor for Translational Research. Dr. Cominelli has been also an outstanding mentor and has trained more than 120 individuals many of them being independent investigators or academic leaders in Gastroenterology.

Dr. Cominelli is also a highly respected clinician with strong expertise in clinical program development for the diagnosis and treatment of patients with digestive diseases. He has been named “American Top Doctor” in Gastroenterology by Castle Connonly Medical Ltd (2001-2016), “Best Doctor” in Gastroenterology, by the Cleveland Magazine (2009-2016), “Best Doctor in Gastroenterology (top 1%)”, by US News & World Report (2012-2016) and “Super Doctor in Gastroenterology” by Key Professional Media (2012-2016).