Grant: CIHR Fellowship

Colorectal cancer (CRC) is the third most common cause of malignancy and second most common cause of cancer death. There are a wide range of therapy available for colorectal cancer, but treatment becomes complicated as there are a range of colon cancer subtypes. Subtypes of cancer respond to therapy differently, as a result there is increased risk of recurrence and metastasis. There is a significant reduction of 5-year survival rate for stage-I CRC to stage-IV CRC (90% to 10%). This necessitate to search early biomarkers and improved therapeutic strategy during the early stage of colon cancer progression. Therefore, in cancer research it is crucial to subcategorize the cancer type based on biomarker discoveries which can lead to more effective therapeutic procedures. Chronic inflammation in the form of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis are some of the risk factors for tumor progression in colon. Our lab works with a family of protein called Cdx1 and 2.They are present in high load in the gut. These proteins are crucial for gut development and maintenance. Moreover, Cdx2 is considered as a marker for advanced colon cancer. My preliminary work suggests loss of Cdx protein is linked to aberrant inflammation. I have found that Cdx protein directly regulates production of a protein named Trim31, which has anti-inflammatory properties. Thus, loss of Cdx or Trim31 proteins lead to chronic inflammation in the gut which in turn promotes tumor formation. My study aims to identify the cellular functions and pathways that are affected by the loss of Cdx and Trim31 proteins; and to find out the factors and inflammatory cues that are playing important roles in this imbalance., Thus, this study will reveal a novel roadmap that leads to chronic inflammation and colon cancer formation. ; and may serve as a blueprint for developing improved therapeutic strategy for colon cancer.