Cancer

The Blelloch lab’s main interests are in the transcriptional/epigenetic regulation of cell fate in early mammalian development spanning from the oocyte to early gastrulation. These interests include the role of transcription factors, chromatin regulators, and microRNAs. The lab more recently developed an additional focus on the molecular control of antitumor immunity, including the role of exosomes.

We use synthetic biology and high-throughput functional genetic screens to expand our ability to interrogate and manipulate the immune system. Our new tools for understanding antigen presentation and T-cell recognition are being applied to cancer and other diseases with the goal of developing new immunotherapies and better implementing existing ones.

CaPSURE: UCSF Cancer of the Prostate Strategic Urologic Research Endeavor CaPSURE™ is a longitudinal, observational study of approximately 15,000 men with all stages of biopsy-proven prostate cancer. Patients have enrolled at 43 community urology practices, academic medical centers, and VA hospitals throughout the United States since 1995

Our research group is focused on refining pre-clinical models to study treatment resistance to novel targeted therapies against bladder and prostate cancer. We leverage high throughput, genome wide CRISPR screens to examine drug resistance and identify regulation of surface target expression. In collaboration with the Department of Urology at UCSF, we are developing a robust biobank of patient derived tumor tissues including fresh and archival tissue. We are conducting correlative studies in neoadjuvant clinical trials for high risk prostate cancer for future biomarker and model development.

The Gilbert laboratory's expertise is in synthetic biology, functional genomics and cancer biology. We are interested in new ways to model and overcome drug resistance in prostate cancer, hematopoietic malignancies and lung cancer. We use genome scale screens, genetic interaction mapping and genome engineering to model and map the genetic and epigenetic causes underlying why some patients are cured and others are not by cancer therapy. We are also building new CRISPR tools to edit the epigenome which will allow us to manipulate gene expression in new ways.

Current research focuses include stem cell research, the molecular mechanisms of impotence, molecular mechanisms of female stress urinary incontinence, molecular mechanisms of Peyronie's Disease, molecular mechanisms of PDE5A gene regulation, molecular marker of prostate and bladder cancer and roles of integrins in cancer and urological diseases.

Our research team is dedicated to identifying modifiable factors that improve quality of life and clinical outcomes in individuals who have been diagnosed with cancer.

Our research group is aiming to cure more cancer with PSMA-guided fluorescence robotic prostatectomy. We are investigating the use of PSMA-guided ablation as a focal therapy and pioneering breakthroughs in treating metastatic prostate cancer

The overarching scientific goal of the Prostate Cancer Program is to use a team approach to advance the understanding of tumor biology and drive translation into more effective and targeted treatment. This is done through translational research spanning discovery bench science to clinical application and back. The program also seeks to address the burden of prostate cancer and disparities in outcomes among patients within the catchment area.

The Quigley lab studies how targeted cancer therapy works and why it stops working. We particularly focus on understanding how prostate tumors develop resistance to androgen signaling inhibitors. To this end, we identify links between DNA structural variants, epigenetic changes, and patient outcomes by sequencing biopsy samples donated by cancer patients and employing integrative bioinformatics and machine learning methods. Our goal is to reconstruct how the tumor responds to therapy pressure by interrogating the tumor’s genome, epigenome, and transcriptome. With this information, we can understand the biology of lethal cancer, develop new biomarkers to select which patients will respond to therapy, and understand how therapy resistance develops.

Our research has expanded the traditional lines of investigation into cancer biology, uncovering a novel layer of control to gene regulation for cancer initiation at the post-genomic level. We have been at the forefront of realizing that the cancer proteome is profoundly shaped by molecular events downstream of transcription. In particular, across evolution, many host-parasite relationships usurp the translation machinery to drive a tailored protein synthesis program. For example, viruses hijack the host's translation apparatus as a means to drive the selective translation of their own viral mRNAs. Similarly, our research has been fundamental in establishing that cancer cells have usurped the cell's translation machinery. This provides a unique means for production of tailored proteins that selectively fuel cancer cell growth, proliferation and metastasis. Utilizing biochemical, molecular, and genetic approaches within the context of unique animal models, we are uncovering new mechanisms for gene-specific control of mRNA translation vital for cancer initiation. These results have been instrumental in the design of a new generation of compounds that modulate protein synthesis and act as novel therapeutic agents. Presently, there is an unprecedented potential for changing the landscape of cancer therapies with the first targeted molecules for oncogenic-dependent protein synthesis. This reflects a new cancer cell vulnerability that may pave a new, fundamental shift in targeting oncogenic pathways that is less likely to trigger drug resistance.

Dr. Smith’s principal research interests center on cancer, fertility preservation, and cancer treatment effects on male reproductive biology.

The Urologic Outcomes Database records detailed clinical baseline and follow-up data on patients seen and treated for genitourinary cancer at UCSF to enhance clinical care and support research in the department. The database contains data on approximately 7,000 prostate cancer patients, and supports research studies including biomarker discovery, nutritional epidemiology, novel therapeutics, quality of life and high-risk markers. Extensive clinical and pathological data on renal cancer patients is also available. The database is funded intramurally and by the UCSF prostate cancer SPORE grant funded by the National Institutes of Health, National Cancer Institute.