Dingzhi Wang Ph.D.
Research Professor, Biodesign Center for Applied Structural Discovery
My research is focused on understanding the molecular, genetic, and cellular bases for colorectal cancer, with emphasis on understanding how the pro-inflammatory and anti-inflammatory molecules coordinately control tumor cell fate. My long-term goal is to make a contribution in establishing a foundation for personalized colorectal cancer prevention and treatment by determining the mechanisms of colorectal carcinogenesis and characterizing the molecular bases of the individual patient. Since the cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) axis plays a key role in promoting colorectal cancer progression, I have been extensively studying the mechanism(s) by which PGE2 promotes colorectal tumor growth by stimulating cell proliferation, survival, and migration/invasion as well as angiogenesis via multiple pathways. I was the first to identify several novel downstream targets of PGE2 signaling including PPARd and CXCL1 and found that the levels of CXCL1 receptor, CXCR2, is elevated in human colorectal carcinoma specimens as compared to matched normal tissues. My study revealed for the first time that CXCR2 is required for infiltration of MDSCs from circulatory system to colonic mucosa and tumor and MDSCs contribute to colonic inflammation and cancer. As Co-PI of this proposal, my expertise in studies of gene functions and regulations, cell signaling pathways, and animal models of this disease is highly relevant. The current application is a logical extension of my previous works. I plan to continue to address many exciting and challenging questions outlined in the proposed research plan. Answers to these questions will not only enhance our understanding of the molecular mechanisms by which aspirin use reduces CRC risk and mortality, but also have the potential to directly impact the clinical care of patients with CRC.