Arnold Chin, MD, PhD
Project Title: Understanding the Role of Receptor Interacting Protein 2 (Rip2) in Prostate Cancer: Testing a Model System in Dissecting the Prostate Cancer Tumor Microenvironment
Synopsis: Inflammation within the tumor microenvironment can be predictive of tumor stage, cancer-specific survival, as well as response to treatments. In prostate cancer, inflammatory cells are commonly seen juxtaposed to prostate adenocarcinoma. Our goal is in understanding the molecular mechanisms that define the prostate cancer inflammatory microenvironment and believe that it will provide insight into cancer progression and targets for novel therapeutics.
Dolores Di Vizio, MD, PhD
Surgery, Pathology and Laboratory Medicine and Biomedical Sciences, Cedars Sinai Medical Center
Project Title: Large Oncosomes: A Novel Approach to Liquid Biopsy in Patients with Prostate Cancer
Synopsis: An important goal in the prostate cancer field is to distinguish aggressive from indolent cancer in a minimally invasive manner. Preliminary results from our laboratory indicate that tumor-specific extracellular vesicles called “large oncosomes” can be identified in the blood of patients with prostate cancer, and that their genomic make up, as evaluated by next generation DNA sequencing, recapitulates that of the tumor. The aim of this SPORE project is to determine whether the genomic aberrations in circulating large oncosomes can provide information about the likelihood of clinical progression of the disease. Using this strategy we are attempting to develop a new test for early identification of patients who are at high risk of progression and/or resistance to current therapies.
Beatrice Knudsen, MD, PhD
Translational Pathology, Cedars Sinai Medical Center
Project Title: Protein phosphorylation changes in the DNA damage response checkpoint as biomarkers and drug targets in advanced prostate cancer
Synopsis: Aggressive cancer cells suffer insults to their genomes, which need to be repaired. All cells express sensors that report DNA damage to a complex system of enzymes that orchestrate the repair before the cell divides. The DNA damage response (DDR) checkpoint is part of the system andassures that cell division comes to a halt. In cancer cells the DDR checkpoint is often defective, which causes cancer cells to accumulate mutations. Thisproject will apply advanced mass spectrometry and proteomics to assess the defect of the DDR checkpoint in advanced prostate cancers and generate biomarkers for treatment decisions in patients. Certain defects in the DDR checkpoint make cancer cells vulnerable to chemotherapies that possess synergistic effects with DDR checkpoint abnormalities in killing cells. Ourproject brings together a multi-disciplinary group to measure the defects and interpret their biological consequences.
Yi Xing, PhD
Microbiology, Immunology and Molecular Genetics, UCLA
Project Title: Transcriptomic and functional impact of the neuronal splicing factor NOVA1 in prostate cancer
Synopsis: Dysregulated splicing of precursor messenger RNAs represents an important layer of molecular aberration in cancer. Previous work of our group has suggested a potential role of a master splicing regulator NOVA1 in prostate cancer. NOVA1 has been extensively studied as a neuronal-specific splicing regulator but little is known about its function in non-neural tissues. Our project will systematically investigate the transcriptomic and functional impact of NOVA1 in prostate cancer, and may reveal novel molecular markers and therapeutic targets.