Prostate cancer is the most common cancer in US men and the second leading cause of cancer death.  However, most men (about 85%) who are diagnosed with prostate cancer die from other causes.  Distinguishing who will die from prostate cancer and need aggressive treatment options versus those who will live and may need less invasive approaches is a major focus of our research.

We hypothesize that different molecular drivers of prostate cancer confer differences in aggressiveness.  If we can define the causal drivers of aggressive disease men could be stratified based on molecular signatures to different types of therapeutic approaches.  We also hypothesize that different molecular drivers will confer different therapeutic vulnerabilities which can be exploited for targeted therapeutics.

We use multiple approaches to achieve our goals.  To identify molecular drivers of aggressive disease we have mined public genomic databases such as The Cancer Genome Atlas.  To functionally model putative drivers to identify causal relationships we utilize a novel stem cell model of prostate cancer.  Adult mouse prostatic stem cells are manipulated genetically to mimic driver alterations found in human prostate cancer.  These genetically altered cells are grafted into recipient hosts to assess pathological phenotypes.  Wild-type cells make benign ductal structures.  If cells are manipulated with a driver gene alteration then premalignant or malignant pathology is observed.  Once we have identified driver alterations that generate cancerous lesions we can then go back to human clinical datasets for RNA expression to identify targetable pathways. My Lab develops and tests the experimental models.  Jim Costello’s lab does the computational modeling.