The Role of ERRalpha-PGC1alpha-Driven Mitochondrial Alterations Defines the Biological Basis of Prostate Cancer Disparities in African Americans
Abstract
Objective and Rationale: African American prostate cancer patients have higher rates of cancer deaths and shorter survival rates compared to European American patients. While there are many different socioeconomic factors, evidence of biological factors contributing the difference in patient outcomes is apparent; however, these differences have not been fully explored. Our research has found that one of the differences in the prostate cancer patient outcomes of African American and European American patients is in metabolism. Metabolism is carried out in special compartments of the cell called mitochondria. Mitochondria are the powerhouses of the cell. They are responsible for helping the cell to exchange oxygen and other processes involved in cell metabolism. We found changes in metabolism in 26 out of 30 different cancer types, including prostate cancer. We have identified two members of a complex that work together to drive these metabolic changes: ERR-alpha and PGC1-alpha. The overall goal of this project is to learn how this complex promotes cancer progression in African Americans by changes in metabolism, including the increased presence of mitochondria. We believe that this may be the driving wedge in disparities for many cancers in African American patients. We want to look at the protein expression and function of our complex in prostate cancer in both African Americans and European Americans. We want to explore the clinical relevance of our previous findings and investigate the function of this complex in these cancer cells. We plan to use a multitude of methods to study the differences in metabolism, including the use of cancer cell lines and animal models to pinpoint those differences. Applicability of the Research: Our research findings will provide a new understanding for how metabolism can contribute to differences in prostate cancer patient outcomes in African Americans. This may lead to development of better prognostic tests and measures that will not require invasive methods. Our research holds promise for identifying African American prostate cancer patients that have aggressive cancers and provide them with improved targeted cancer therapies. Career Goals of the Principal Investigator: My future career goal is to become an independent researcher at a cancer center and direct a research program that uses basic research to discover novel clinical targets for prostate cancer therapies that address cancer health disparities in disadvantaged populations. I possess a strong drive to learn new scientific concepts and ideas, and I believe that the discovery potential embodied by clinical and translational research will allow me to achieve my research goals and contribute to the prevention, treatment, and cure of cancer. My academic and research training in cancer biology has provided an excellent foundation for me to build a career investigating the complex relationships between the biological, racial, and molecular contributors to cancer disparities. This award will undoubtedly help advance my career by providing new training experiences that expand the scope of my research potential. I will be trained by experts in the field of prostate cancer, including my mentor Dr. Arun Sreekumar, as well as five co-mentors experienced in clinical and translational research. Each of them will be able to train and guide me in their respective professions and overall contribute to my development as a researcher that desires to use basic science and translate them to clinical approaches and treatment for patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110154
Entities
People
- Kimiko L Krieger
Organizations
- Baylor College of Medicine
- United States Army