The Chowers Lab

תמונה ראשית- ChowerLab

Yehuda Chowers Lab

Precision Care for Inflammatory Bowel Disease Patients

Principal Investigator: Professor Yehuda Chowers

The Gastroenterology Research Lab, directed by Professor Chowers is focused on optimizing treatment of inflammatory bowel disease (IBD) patients.

Included amongst the IBDs are Crohn's disease and ulcerative colitis, both of which affect millions worldwide. A generally accepted concept is that tissue damage is caused by immune system activity. However, the etiopathogenesis of IBD remains elusive, therefore therapy is nonspecific and is focused on suppressing immune activity using an array of agents differing in their mechanism of action. A disappointing observation is the overall suboptimal therapeutic outcomes achieved for a variety of agents, whether antibodies or small molecules, affecting different inflammatory pathways.

A large volume of the research performed in the lab is focused on the comprehensive and integrative analysis of factors affecting response to therapy, both at a pretreatment stage and during treatment dynamics. These studies aim to enable the design of personalized, mechanism-based stratification for therapy selection, to gain further insight into mechanisms of non-response to different drugs, and to advance next generation therapies for non-responders based on a personalized therapy scheme

To that end, we employ cell-based, genomics and metabolomics assays to define baseline pretreatment characteristics of the immune, microbial, and metabolic profiles of IBD patients, and correlate these with the response to therapy. We use integrative, system-level analysis of the data generated to identify predictive biomarkers for determing the most effective therapies for patients. We also follow treatment dynamics and combine multi-dimensional microbial and metabolic data to understand the interaction between these factors and their effect on disease pathogenesis.  

In vivo and in vitro experimentation are performed to validate the findings and test biologic interactions between specific factors. This allows examination of potential specific and novel therapeutic approaches.

Meet the Chowers Lab Team>

 

 


Apart from the selection of the most appropriate therapy for a patient, an additional challenge is the appearance of anti–drug antibodies (ADA). These ADA, specifically in the case of biological drugs, greatly hamper therapy which might otherwise have been optimal for the specific patient. Interference with drug activity can result from ADA-mediated increase of its clearance, or by neutralizing its ability to bind the target when the ADA specifically targets the drug binding site. Assessment of disease activity, combined with measurements of both drug levels and ADA, can facilitate rational decisions for management of loss of response, optimization of disease control during maintenance therapy, and possible cessation of treatment.

Our studies are therefore aimed at understanding the mechanisms causing immunogenicity, including the role of drug/target complex formation and the intestinal environment susceptible to ADA formation, and to explore strategies for decreasing immunogenicity in patients treated with biological drugs.

An additional approach for management of ADA development is improvement ADA detection assays. We are developing a means for bedside detection of ADA, in particular neutralizing ADA, which are suspected to be better predictors of loss of therapeutic response. The ability to detect ADA at an early stage may assist in early decision-making related to timely incorporation of immunosuppression into the medical treatment of IBD patients, providing sufficient time for abrogation of ADA, while maintaining a clinical response.

The long term goal of our studies is to devise alternative strategies to prevent ADA generation based on understanding and manipulation of pathophysiologic events which lead to their formation.

Professor Yehuda Chowers

Yehuda Chowers is the director of the Division of Research and the Gastroenterology Institute at Rambam Health Care Campus, and a professor in the Ruth & Bruce Rappaport Faculty of Medicine of the Technion-Israel Institute of Technology.

Professor Chowers earned his B.A. and M.D.  in Medicine from Ben-Gurion University, and conducted his postdoctoral fellowship in the Laboratory of Mucosal Immunology at the University of California at San Diego.

Honors received by Professor Chowers include the American Gastroenterology Association Advanced AGA Research Training Award.  He is also a two-time winner of the Chaim Sheba Medical Center’s Award for Excellence in Research.

Professor Chowers is a member of the European Crohn’s and Colitis Organization (ECCO), the American Gastroenterology Association, the Israel Gastroenterology Association, and the Israel Medical Association.  He was a member of the ECCO Scientific Committee, the assigned representative of ECCO to the European Gastroenterology Association Scientific Committee, and former chair of the Israeli IBD society. He serves on the editorial board of Alimentary Pharmacology & Therapeutics, was an associated editor for the Journal of Crohn’s and Colitis, and is a member of the editorial board for Gut.

Professor Chowers’s research interests are focused on personalized therapy of inflammatory bowel diseases based on understanding drugs mechanisms of action, immunogenicity and therapeutic drug monitoring of biologics, and the interplay between bacteria and the mucosal immune system. He is performing additional research to understand mechanisms of radiation-induced bowel injury and means to prevent it.

He has co-authored more than 160 papers in professional journals including basic research, clinical research articles, guidelines, case reports, and review papers.  Professor Chowers has been a lead presenter and guest speaker at conferences worldwide, and served on the organizing committees for a number of professional international conferences.

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