Role of ATDC in the Regulation of Antioxidant Response in Pancreatic Cancer
Abstract
With my doctoral and ongoing postdoctoral training, I have a strong foundation and an experience of more than 8 years in the field of pancreatic cancer research. My ultimate career goal is to be an independent, fully tenured professor at an academic institution and do impactful translational pancreatic cancer research. The Peer Reviewed Cancer Research Program Horizon Award will greatly benefit me in advancing my current research and competing for future funding, which will ultimately be important for me to continue as an independent investigator. I foresee my research focus remaining strongly on pancreatic cancer research, with a continued focus on how pancreatic cancer cells utilize various nutrients/fuel sources to favor growth and survival, while inhibiting harmful free radicals. Pancreatic cancer is a deadly malignancy, with the lowest 5-year survival rate of any cancer. Indeed, most patients diagnosed with this disease will perish within a year of diagnosis. Early spread, rapid growth, and lack of effective therapies make the detailed understanding of pancreatic cancer biology highly important. Our lab has done pioneering work in understanding Ataxia telangiectasia group-D complementing gene (ATDC), a widely overexpressed protein in pancreatic cancer. Previous research has established that ATDC has key role in initiation, growth, spread, and therapy resistance in pancreatic cancer. Rapidly dividing cancer cells generate harmful free radicals, which if accumulated can paradoxically kill cancer cells. Our preliminary data show that ATDC provides protection against these free radicals and therefore favor cancer cell survival and growth. Since no therapies are yet available to target this crucial protein, understanding how ATDC protects cancer cells and how this protein favors pancreatic cancer growth will result in discovery of new drugs for this fatal malignancy. Along with excellent scientific feedback/support and mentorship from a panel of leading pancreatic cancer researchers, I have the benefit of the robust research environment at the University of Michigan, especially in the area of pancreatic cancer. These factors along with my ongoing training with the Simeone group, who have been pioneers in understanding ATDC protein, will help me in the completion of proposed studies. For these studies my objectives will be (1) to uncover how ATDC reduces harmful free radicals in pancreatic cancer cells and (2) how ATDC changes the utilization of nutrients/fuels to favor cancer cells growth. I have found that ATDC regulates the levels of NRF2, a protein, which is both, inhibitor of free radicals and favors cell growth. Discovering how ATDC regulates NRF2 will result new therapies to inhibit pancreatic cancer. Being a trainee and member of interdisciplinary team of researchers in the translational oncology program, headed by my advisor, Dr. Diane Simeone, the outcome of my studies will be directed to clinical trials that would result in rapid availability of new drugs to pancreatic cancer patients within next 5 years. Due to higher rates of smoking and diabetes along with an increased exposure to carcinogens, Service members and Veterans have a higher risk of developing pancreatic cancer. With most available medicines giving marginal to no survival benefits to pancreatic cancer patients, development of targeted therapies is highly important. The outcome of my proposed studies will not only improve the current understanding of ATDC in pancreatic cancer but also allow the discovery new and potentially effective therapies, which will be beneficial to all pancreatic cancer patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710497
Entities
People
- Vinee Purohit
Organizations
- United States Army
- University of Michigan