Florian Rieder, M.D.

Staff

Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Location:NC2-118
riederf@ccf.org
Phone: (216) 445-4916
Fax: (216) 636-0104



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.


Dina  Dejanovic BA
Dina Dejanovic BA
Research Technologist

Location:NC2-119
Phone:(216) 445-4916
dejanod@ccf.org
Fax:(216) 636-0104
laboratory

Satya  Kurada M.D.
Satya Kurada M.D.
Staff

Location:NC2-119
Phone:(216) 445-9416
kuradas@ccf.org
Fax:(216) 636-0104
laboratory

Ren  Mao M.D., Ph.D.
Ren Mao M.D., Ph.D.
Research Scholar

Location:NC2-119
Phone:(216) 445-4916
maor@ccf.org
Fax:(216) 636-0104
laboratory

Shuai  Zhao MS
Shuai Zhao MS
Research Technologist

Location:NC2-119
Phone:(216) 445-4915
zhaos@ccf.org
Fax:(216) 636-0104
laboratory


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