Florian Rieder, MD
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 445-5631
The inflammatory bowel disease (IBD) course is highly heterogenous. Intestinal fibrosis causing clinically apparent stricture formation is a common feature of both entities of IBD, Crohn’s disease and Ulcerative colitis and leads to a significantly impaired quality of life in affected patients, intestinal obstruction as well as need for surgical intervention. This constitutes a major treatment challenge, suppression of inflammation and the emergence of stronger immunosuppressive medications can only minimally reduce the incidence and prevalence of fibrostenosing IBD and no specific anti-fibrotic therapy is available.
Fibrosis results from the response of gut tissue to the insult inflicted by chronic inflammation. The underlying fibrogenic mechanisms are complex and dynamic, involving multiple cell types, interrelated cellular events, and a large number of soluble factors. These features are shared across organs, such as liver, skin, kidney or heart. Owing to a breakdown of the epithelial barrier in IBD, luminal bacterial products leak into the interstitium and induce an innate immune response mediated by activation of both immune and non-immune cells. Damage-associated molecular patterns, intracellular components released by necrotic cells, can also induce mesenchymal cell activation and contribute to stricture formation. Fat wrapping around the bowel wall, the so-called ‘creeping fat’, typical of Crohn’s disease, can drive fibrogenesis through the release of free fatty acids that induce intestinal muscle cell proliferation. Clinical and experimental evidence indicates that once fibrosis is established it can progress independently of inflammation. The composition of the intestinal extracellular matrix, its mechanoproperties and matrix bound factors are dramatically altered in chronic gut inflammation and can actively promote fibrosis. Identification of the unique mechanisms of intestinal fibrogenesis should create a practical framework to target and blockade specific fibrogenic pathways.
Our group focusses on the discovery of novel mechanisms of intestinal fibrogenesis, the prediction of fibrostenosing disease courses and innovative ways to treat IBD patients with established strictures. For this purpose, we are using primary human cells, tissues and organ culture systems as well as novel animal models of intestinal fibrosis. We have established an IBD biomarker cohort and assess endoscopic techniques to treat fibrostenosing IBD.
Rieder F., Cheng L., Harnett K.M., Chak A., Cooper G.S., Isenberg G., Ray M., Katz J.A., Catanzaro A., O`Shea R., Post A., Wong R., Sivak M.V., McCormick T., Phillips M., West G.A. Willis J.E., Biancani P., Fiocchi C. GERD-associated esophagitis induces endogenous cytokine production leading to motor abnormalities. Gastroenterology (2007) 132:154-65
Rieder F., Brenmoehl J., Artinger M., Georgieva M., Obermeier F., Rogler G. Prostaglandin E2 reduced migration of intestinal myofibroblasts. Inflamm Bowel Dis (2010) 16:1505-13
Rieder F., Kessler S., West G.A., Bhilocha S., dela Motte C., Saddler T.M., Gopalan B., Stylianou E., Fiocchi C. Inflammation-induced Endothelial-to-Mesenchymal Transition: A Novel Mechanism of Intestinal Fibrosis. Am J Path (2011) 5:2660-73
Rieder F., Nonevski I., Ma J., Ouyang Z., West G., Protheroe C., DePetris G., Schirbel A., Lapinski J., Goldblum J., Bonfield T., Lopez R., Harnett K., Lee J., Hirano I., Falk G.W., Biancani P., Fiocchi C. Th2 Cytokines, TGF-b1 and eosinophil products induce fibrogenesis and alter muscle motility in eosinophilic esophagitis. Gastroenterology (2014) 5:1266-77
Rieder F., Fiocchi C., Rogler G. Mechanisms, Management and Treatment of Fibrosis in Patients with Inflammatory Bowel Diseases. Gastroenterology (2017) 2: 340-50
The National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, has awarded Florian Rieder, MD, a 5-year, $2 million grant to explore new mechanistic understandings of intestinal strictures and their link to the development of creeping fat in patients with Crohn’s disease (CD). This is the first R01 grant awarded to Dr. Rieder, a physician-scientist and staff member in the Departments of Inflammation and Immunity and Gastroenterology, Hepatology and Nutrition (part of the Digestive Disease & Surgery Institute).
Florian Rieder, MD, Assistant Staff, Department of Inflammation & Immunity, was awarded the 2019 Sherman Emerging Leader Prize for his early career contributions to the fields of inflammatory bowel disease research and care. The prestigious award was presented at the 2019 Advances in Inflammatory Bowel Diseases annual conference.
Cleveland Clinic has been named the coordinating center for a new $4.3 million grant from the Leona M. and Harry B. Helmsley Charitable Trust to accelerate the development of new anti-fibrotic therapies for patients with Crohn’s disease. This consortium award will be split among Cleveland Clinic, Mayo Clinic and Robarts Clinical Trials.
A new internally funded award, called the Co-Laboratories Award, encourages new, "start-up" collaborations that bring together researchers from different laboratories to investigate and attack disease from many angles, drawing on the unique expertise and innovations that each laboratory has to offer. The award provides up to $100,000 in project funding per year for up to two years. In its inaugural year, the award funded two exciting cross-disciplinary projects that will investigate neuronal dysfunction in alcohol abuse and smooth muscle hyperplasia in Crohn's disease.