The role of an important protein in the regulatory pathway that is involved in limiting colon inflammation and tumor growth has been discovered by researchers.
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.
‘Chronic inflammation can lead to Crohn's disease and ulcerative colitis. Key protein involved in the colon inflammation has been identified by researchers.’
"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.
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.