The Quigley Lab is located at the Helen Diller Family Comprehensive Cancer Center, part of University of California San Francisco.

About the Quigley lab

Metastatic prostate cancer is unfortunately a lethal disease. Although powerful targeted chemotherapies have improved outcomes for patients, most metastatic prostate tumors develop resistance to these therapies and progress to metastatic castration-resistant prostate cancer (mCRPC). This progression is driven by evolutionary changes the tumor's genome and gene activity patterns that enable the disease to survive in the presence of therapy. There is a critical need to understand how diseases like mCRPC respond to therapy in order to develop novel approaches to target this disease and make better use of the tools we already have.

Our lab studies tumor biopsies donated by cancer patients using molecular assays and computational methods for genome analysis. Our goal is to reconstruct how the tumor formed and changed by interrogating the tumor’s genome (DNA mutations and structural variation), epigenome (DNA methylation and shape), and transcriptome (gene activity levels). 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.

We don't work alone! Our lab practices team science in close collaboration with physicians and laboratory investigators. Many of our studies were made possible through the Prostate Cancer Foundation-funded West Coast Dream Team collaboration. Most of all, we are grateful to the generous and thoughtful contributions of men living with prostate cancer who choose to donate their time and tissue to our studies.

Key publications

Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer
(Quigley et al. Cell 2018)
This study (led by my colleague Felix Feng) was the first large-scale whole genome and transcriptome analysis of mCRPC tumor biopsies. We performed integrated analysis of DNA and RNA from 101 metastatic prostate cancer whole genomes. We showed an enhancer region affects the Androgen Receptor in approximately 80% of mCRPC and demonstrated how DNA repair defects associated with loss of BRCA2, CDK12, and TP53 are associated with genomic scars of deletions, tandem duplication, and chromothripsis.

The DNA methylation landscape of advanced prostate cancer
(Zhao et al. Nature Genetics, 2020)
This study (led by my colleague Felix Feng and co-led by our group) was the first large whole genome analysis of methylation in metastatic prostate cancer. We performed whole genome methylation analysis on 100 metastatic prostate tumors, extending our investigation of the cohort we published in (Quigley et al Cell 2018). We observed that 22% of tumors have a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF. We also identified intergenic regions where methylation is associated with RNA expression of the oncogenic driver genes AR, MYC and ERG. Finally, we showed that differential methylation during progression preferentially occurs at somatic mutational hotspots and putative regulatory regions.

The genomic and epigenomic landscape of double-negative metastatic prostate cancer
(Lundberg et al. Cancer Research 2023)
Prior work from the West Coast Dream Team (e.g. Aggarwal et al. 2019, Zhao et al 2020, Sjöström et al. 2022) and other groups has shown that mCRPC tumors can shift their transcriptional and epigenetic phenotype to alternative lineages. This shift is linked to worse patient outomes and resistance to AR-targeted therapies. In this study, we comprehensively characterized treatment-emergent mCRPC by integrating matched RNA sequencing, whole-genome sequencing, and whole-genome bisulfite sequencing from 210 tumors. Tumors with the AR-/NE- lineage were clinically and molecularly distinct from other mCRPC subtypes, with the shortest survival, amplification of the chromatin remodeler CHD7, and PTEN loss. Genome-wide methylation analysis nominated KLF5 as a driver of the AR-/NE- phenotype, and KLF5 activity was linked to RB1 loss. These observations reveal the aggressiveness of AR-/NE- mCRPC and could facilitate the identification of therapeutic targets in this highly aggressive disease.