Biological Characterization and Clinical Utilization of Metastatic Prostate Cancer-Associated lincRNA SchLAP1
Abstract
Scientific objective and rationale of proposed study: Prostate cancer is one of the leading causes of cancer-related deaths in the United States among men and the most commonly diagnosed cancer in American males. Most prostate cancer-related deaths are due to progression to advanced disease; therefore, identifying a novel biomarker for advanced prostate cancer and uncovering the molecular mechanism of disease progression will significantly benefit prostate cancer patients. Using next-generation sequencing data from hundreds of prostate cancer tumors, our laboratory has identified SChLAP1 (Second Chromosome Locus Associated with Prostate-1) as a novel biomarker and potential therapeutic target of aggressive prostate cancer. SChLAP1 is a long noncoding RNA (lncRNAs) that have been implicated in various biological, developmental, and pathological processes. Our previous studies suggested that SChLAP1 might bind to and abrogate the tumor suppressive complex (SWI/SNF complex), but the precise mechanism by which SChLAP1 mediates the dysfunction of SWI/SNF complex and the downstream effects are poorly understood. In this study, we propose to elucidate the mechanism of SChLAP1-mediated abrogation of SWI/SNF function in prostate cancer progression that will extend our understanding of prostate cancer biology, and importantly, aid in the development of novel therapeutic strategies that target SChLAP1 and its downstream factors. Applicability of proposed research: The proposed project will utilize cutting-edge technologies to test our hypotheses about the mechanism of SChLAP1-mediated loss-function of SWI/SNF complex and potential clinical utilization of targeting SChLAP1 in prostate cancer. Uncovering the mechanism of SChLAP1-mediated abrogation of SWI/SNF complex will help us to understand the role of SChLAP1 in prostate cancer progression. More importantly, we will try to translate our findings into novel clinical tools and therapeutics that could significantly benefit prostate cancer patients with aggressive disease. Overall, this project will advance our knowledge of the role of lncRNAs in metastatic prostate cancer and offer novel therapeutic strategies for prostate cancer treatment. Goals and training plan: Coming from a family of doctors, being a medical scientist has been my goal since childhood. I was intrigued by cancer research as an undergraduate student, which led me to pursue my Ph.D. and postdoctoral training as a cancer researcher in Dr. Arul Chinnaiyan s lab. The Chinnaiyan s lab is an excellent environment for conducting cutting-edge research and career development. The lab is composed of a team of multidisciplinary scientists who work together to solve biological problems using various approaches and expertise. Being in this environment will provide me the opportunity to obtain valuable research skills as well as increase my depth and breadth of knowledge. The proposed project is expected to be completed in a timeframe of 2 years, resulting in high-impact publications. Working on the proposed project will lead to a more thorough understanding of the biological role and clinical potential of metastatic prostate cancer-associated lncRNAs and provide valuable experience and training required to transition into an independent researcher.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610195
Entities
People
- Lanbo Xiao
Organizations
- United States Army
- University of Michigan