Exploring the Role of snoRNAs in Prostate Cancer Progression and Therapeutic Resistance
Abstract
Prostate cancer is the second leading cause of cancer-related death in US men. While advances have been made in recent years, mortality from advanced stage disease continues to take the lives of thousands each year. Improving our understanding of the mechanisms driving prostate cancer progression and the development of treatment resistance are urgently needed to address this daunting medical problem. My proposed studies aim to characterize the role of small nucleolar RNAs (snoRNAs) in these tumors. It is thought that tumors must upregulate protein synthesis for survival and sustained proliferation. snoRNAs perform a number of actions but most notably are needed for cells to efficiently synthesize proteins, which allow for proper cellular function. Emerging evidence suggests that snoRNAs play key roles in prostate cancer, but much research is needed to fully appreciate their contribution to the disease and whether they may serve as novel therapeutic drug targets. Our preliminary data suggest that snoRNAs not only promote prostate cancer cell survival but also progression to a drug-resistant state. Thus, I will explore the role of snoRNAs in prostate cancer progression, work to understand how they mechanistically function, and assess whether they mediate resistance to currently available treatments. Additionally, I will undertake experiments to begin to determine whether snoRNAs may be targeted for therapeutic benefit. This research will expand our understanding of a relatively new field in prostate cancer research and will take a completely novel approach to exploring treatment resistance. My potential findings may provide new avenues to treat advanced stage, terminally ill patients. Patients who fail conventional therapies are ultimately left with few or no remaining options. The development of new medications targeting snoRNAs that decrease cancer cell viability and re-sensitize them to conventional therapy would lead to improved patient outcomes. Successful completion of this proposal will greatly enhance our understanding of this disease, and it is expected that it will lead to the elucidation of several new drug targets with potential for therapeutic development. My career aspiration is to become an independent prostate cancer researcher performing cutting-edge, lifesaving research. Upon completion of this work and award, I will seek tenure-track faculty positions at top-tier institutions. The research plan described in this application will provide me with the opportunity to ask key questions regarding the mechanisms driving progression and resistance in prostate cancer. I will be working in an area where few other researchers are studying, thus providing the chance to become an expert in an emerging field. I will be challenged both to hone my current skill set and add new experience including that with bioinformatics, sequencing, flow cytometry, and in vivo preclinical modeling. These skills will augment my potential for a transition to independence. My mentor, Dr. Allen Gao, is a respected prostate cancer researcher with a successful track record both in making groundbreaking discoveries in the field of prostate cancer research and in mentoring young scientists to independence. This is evidenced by past members accepting faculty positions at renowned institutions. The training environment at the University of California, Davis will provide more than adequate resources including core facilities, collaboration opportunities, and various educational resources that I can use to enhance my skills. I expect to become a competent and highly capable scientist during my postdoctoral studies, and I am eager to continue working towards an end for prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710135
Entities
People
- Alan P. Lombard
Organizations
- United States Army
- University of California, Davis