The Development Research Program is another method of expanding discovery within the SPORE. Each year, three to four highly innovative proposals will be funded with the possibility of an additional year funding extension. Funding will be primarily for new and innovative ideas, but also to initiate short term collaborations, especially with investigators within the SPORE and in other SPORES. Sufficient expertise within the Institution or from interaction with other SPOREs must be demonstrated to show potential for development of a new major theme or research within the SPORE. The proposed projects need not be directly translational, but should have the potential to ultimately lead to translational research.
The UCLA SPORE in Prostate Cancer would like to congratulate the 2016-2017 Developmental Research Program awardees. This year’s projects come from various departments across campus, and exemplify translational research.
Douglas L. Black, PhD
Microbiology, Immunology, and Molecular Genetics, UCLA
Project Title: Identification of Myc-dependent, prostate cancer-specific mRNA splicing events as neo-antigens for antibody and TCR therapy development.
Synopsis: Our project is to identify changes in alternative splicing that are controlled by the Myc and N-Myc oncogenes in prostate cancer. By characterizing how the Myc proteins control gene expression at the level of splicing, we can identify potential new targets for both chemo- and immunotherapeutics.
Andrew S. Goldstein, PhD
Molecular & Medical Pharmacology, Urology, UCLA
Project Title: Role of metastasis-associated microRNAs in prostate cancer (renewal of funding)
Synopsis: In an effort to understand the factors that contribute to aggressive prostate cancer, we looked for differences between tumors which remained localized in the prostate and tumors which had spread beyond the prostate. Of note, we identified a set of very short sequences of RNA, called microRNAs, that were specifically found in tumors which had spread outside of the prostate. Our project is focused on a particular microRNA that we hypothesize enhances the invasive capacity of prostate cancer cells and promotes metastasis. We anticipate that in studying the function of this microRNA we will better define the way that tumor cells become aggressive.
Thomas Graeber, PhD
Molecular & Medical Pharmacology, UCLA; UCLA Metabolomics Center; Crump Institute for Molecular Imaging; Jonsson Comprehensive Cancer Center; California NanoSystems Institute
Project Title: Genomic Instability as a Therapeutic Opportunity in Lethal Neuroendocrine Prostate Cancer
Synopsis: In an effort to discover therapeutic targets for patients with small cell prostate cancer, Dr. Thomas Graeber delves into disruptions of cells at the genome level. Although chromosome instability has long been recognized as a marker of advanced prostate cancer, our understanding of what exactly disrupts the genome and how that experience contributes to aggressive cancer is limited. Dr. Graeber takes a systematic approach to identify genes and mutations associated with chromosome instability, seeks to expose the culprits that cause a volatile environment on the genome, and develop targeted therapies that will inhibit this behavior. This body of work will add to the drugs targets already being tested in patients at UCLA and elsewhere.
Kendall N. Houk, AB, AM, PhD
Chemistry and Biochemistry, UCLA
Project Title: Computational Studies for Understanding Antagonistic Mechanism of Androgen Receptor: Toward Discovery of Novel Therapeutic Agents in Prostate Cancer
Synopsis: We will conduct a series of computational studies to delineate the structural basis of the actions of the androgen receptor (AR) antagonists. Using structural modeling and molecular dynamics (MD) simulations, we will identify the binding modes of the antagonists and quantify the structural changes of the AR upon binding of the ligands. Based on computational studies, we will establish a structure activity relationship (SAR) model that will aid further development of therapeutic agents for prostate cancers.