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Research Identifies Key Protein That May Prevent Colon Inflammation and Tumor Growth

Baylor Scott & White immunologists’ paper published in Nature Immunology

Venuprasad Poojary, PhD, an associate investigator at Baylor Institute for Immunology Research (BIIR), part of Baylor Scott & White Research Institute, reported this week in the journal Nature Immunology the role of a key protein in the regulatory pathway that is involved in limiting colon inflammation and tumor growth. The paper, titled “Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-gt ubiquitination,” is available online in advance of the print edition.

Dr. Poojary focused on how the ubiquitin ligase protein, referred to as Itch, controls colonic inflammation. Inflammation is a protective response to microbial infection and tissue injury. However, uncontrolled inflammation is a major risk factor for the development and growth of colon cancer, which is the main cause of cancer-related deaths in the US. Uncontrolled expression of interleukin 17 (IL-17), an inflammatory growth cell, in the intestinal mucous membrane is associated with inflammation and colon cancer. However, the mechanisms by which IL-17 production is regulated remain unclear.

“We found that deficiency in the Itch protein led to spontaneous colitis and increased susceptibility to colon cancer. Our biochemical analysis revealed that Itch targets ROR-gt (a protein that induces IL-17 expression) for degradation, which reduces intestinal inflammation and inhibits colon cancer growth. Thus, we have discovered a novel regulatory mechanism that inhibits colonic inflammation and carcinogenesis,” Dr. Poojary said.

Chronic inflammation can lead to inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis, which greatly reduce the quality of life of patients. IBD patients also are at high risk of developing colon cancer. Further supporting the role of Itch and the regulation of IL-17, patients with stage I/II colon cancer who have high levels of IL-17 are much less likely to have disease-free survival. According to Dr. Poojary, the new findings will lead to specific targeted therapies and their direct delivery to the site of inflammation in IBDs and colon cancer.

Dr. Poojary started his studies on protein ubiquitination in the Division of Cell Biology at La Jolla Institute for Allergy and Immunology in San Diego, Calif. Since joining BIIR in 2013, Dr. Poojary has developed several projects to identify key regulatory mechanisms in the immune system with the goal of targeting these pathways to treat human inflammatory disorders. Some of his projects are currently funded by the American Cancer Society, Cancer Prevention Research Institute of Texas (CPRIT) and Baylor Charles A. Sammons Cancer Center.

About Baylor Scott & White Health

Formed from the 2013 merger between Baylor Health Care System and Scott & White Healthcare, the system referred to as Baylor Scott & White Health is the largest not-for-profit health care system in the state of Texas. With total assets of $9 billion* and serving a population larger than the state of Georgia, Baylor Scott & White Health has the vision and resources to provide its patients continued quality care while creating a model system for a dramatically changing health care environment. The system now includes 48 hospitals, more than 900 access points, 6,000 active physicians, and 40,000 employees, plus the Scott & White Health Plan, Baylor Scott & White Research Institute and Baylor Scott & White Quality Alliance — a network of clinical providers and facilities focused on improving quality, managing the health of patient populations, and reducing the overall cost of care. For more information visit:BaylorScottandWhite.com

* based on unaudited 2015 fiscal year statements


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Kristine Hughes