CHD1-Deficiency Engenders a Distinct Epigenetic Profile in Castration-Resistant Prostate Cancer
Abstract
Scientific Objective and Rationale: Prostate cancer is one the most common malignancies of adult males in the United States. There are currently 3.3 million diagnosed men, and roughly 160,000 new cases will be made in 2017. The advancement of next-generation sequencing technology has made looking at DNA changes in tumors more common in clinical settings. Information relating to tumor DNA changes is highly valuable, as it can be used to predict patient response to prostate cancer therapies. This proposal will examine the role one of the most frequent gene alterations in CHD1 (chromodomain-helicase DNA binding protein 1) plays as a driver of cancer. We will test whether it alters a series of enzymes that may be targets for cancer therapy. Research Applicability: This research is aimed primarily at advanced-stage prostate cancer patients to use their tumor biology to better tailor prostate cancer treatments. In a clinical setting, the knowledge gained from this proposal could be used to better predict which patients will be responsive to a targeted therapy, thus mitigating any potential adverse consequences associated with the therapy. Currently, therapeutic compounds targeting one of the aspects of prostate cancer tumor biology this proposal examines are being developed. Therefore, it can be expected that, when these compounds are being used to treat prostate cancer patients, the insights this proposal provides can be used as a determinant for their application. In the interim, the information gained from this proposal can be used to create an enhanced molecular understanding of the biology of late-stage prostate cancer. Research Training Plan: This proposal will further my career in several important ways. First, the training described within will provide me with an exposure to new techniques, including genetic engineering and mass spectrometry analysis. Second, the benefit of Dr. Jarrard’s superior mentorship and excellent resources, as well as collaborations at the University of Wisconsin Carbone Comprehensive Cancer Center, will provide an outstanding environment to hone my technical skills and form a strong foundation to develop a scientific career in prostate cancer research. Of significance is the unique opportunity to learn about the pathophysiology of prostate cancer through interactions with physician researchers. I will also benefit greatly from interactions with my co-mentor, Professor John Denu, Ph.D. Professor Denu has years of experience in the field of epigenetics and chromatin regulation and has worked with Dr. Jarrard on a number of projects relating to prostate cancer. His additional mentorship and guidance will prove highly valuable during the course of this award. Career Goals: These interactions will provide me with a stimulating environment to generate information regarding the epigenetic mechanisms regulating prostate cancer progression that will be a basis for a career in prostate cancer research. Preparing the current proposal as the Principal Investigator has not only helped me learn grantsmanship; it also has provided me the initial experiences necessary to become an independent investigator in the area of prostate cancer research. Finally, it is my career goal to continue researching epigenetic regulation of gene expression programs so that these can be exploited and targeted to develop novel prostate cancer therapies. I envision this occurring in an academic setting, so I anticipate applying for an assistant professorship position following the completion of this award.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910245
Entities
People
- Joseph Gawdzik
Organizations
- United States Army
- University of Wisconsin–Madison