Dissecting the Interface Between ARID1A and mRNA Translation in Bladder Cancer
Abstract
Bladder cancer is the fourth most common cancer in the Department of Veterans Affairs (VA) health system. Men are approximately three times more likely to be diagnosed with bladder cancer than women and twice as likely to die from bladder cancer. Occupational and environmental exposure to carcinogens are risk factors for bladder cancer, but tobacco is considered as one of the leading causes of this highly prevalent disease. Recent evidence also associates bladder cancer with Agent Orange exposure. Moreover, bladder cancer remains an economic burden to our society, as it is the most expensive cancer to treat and monitor upon diagnosis. This is in part because bladder cancer is significantly understudied with very limited therapeutic breakthroughs over past 30 years. Most research in the bladder cancer field has focused on DNA and RNA as drivers of disease. However, this has left the process of protein synthesis significantly understudied. Importantly, there is significant emerging work demonstrating that protein synthesis is important for the development of cancer. We propose to comprehensively study the role of a commonly mutated gene called ARID1A in normal bladder tissue maintenance and cancer formation from the vantage point of protein synthesis. To achieve this goal, we will use mouse models and bladder-specific carcinogens to study cancer development and progression in absence of ARID1A, which greatly influences global protein synthesis levels. Moreover, we will also conduct drug trials in patient-derived tumor models using a chemotherapy called Homoharringtonine, which is already approved for blood cancers and can specifically block the process of protein synthesis. Together, these studies are designed to help us understand how abnormal protein synthesis drives cancer development and define a potential new therapeutic option to treat bladder cancer patients. We believe these goals can be achieved within 2-3 years. I have a significant background in microbiology, biochemistry, and RNA biology and intentionally sought to apply these skills in the context of human disease. As such, I joined Dr. Andrew Hsiehs laboratory as a post-doctoral fellow 1.5 years ago at the Fred Hutchinson Cancer Research Center. This experience has allowed me to apply my fundamental skill set to a disease process that is impacting thousands of military individuals today. Support from the Department of Defense Peer Reviewed Cancer Research Program Horizon Award will enable me to devote a significant amount of time to address the important question of how abnormal protein synthesis directs bladder cancer formation and also define a potential new therapeutic target. In addition, the training I will receive from both Drs. Hsieh and Black will enable me to learn how to study bladder cancer through animal models and computational approaches. To this end, I will also take courses in bioinformatics and attend bladder cancer focused conferences. This opportunity will not only help me grow my basic science knowledge, but also help me develop collaborative networks with other labs in this field as I pursue my dream to become an academic scientist. In addition, I will also take courses in grant writing and leadership training. Finally, the grant will give me an opportunity to contribute to the military community with the aim to reduce pain and suffering caused by this disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910658
Entities
People
- Sujata Jana
Organizations
- Fred Hutchinson Cancer Center
- United States Army