Our major projects make use of high-throughput sequencing to study viral infections in various disease states. Polyomaviruses and papillomaviruses are ubiquitous non-enveloped DNA viruses that can cause cancer in humans. Polyomaviruses upregulate the mutagenic enzyme APOBEC3B through direct effects of the large tumor antigen. Additionally, polyomavirus genomes show the scars of a long-term evolutionary conflict with these antiviral mutagenic enzymes. In a recent study, we showed evidence for acute APOBEC3 mutagenesis of the viral genomes present in kidney transplant recipients suffering from BK polyomavirus-associated nephropathy.

Solid organ transplant recipients are at an increased risk for developing bladder and kidney cancers, especially if they have a previous history of BK viremia. A growing body of evidence supports the idea that BK polyomavirus plays a causal role in bladder cancer carcinogenesis. In collaboration with Eric A. Engels, M.D., M.P.H., of the Division of Cancer Epidemiology & Genetics, we are studying the genomic and transcriptomic features of bladder cancer and how these correspond to the presence of DNA tumor viruses and possible mechanisms of tumorigenesis.

Our group enjoys an extensive range of collaborations with other NIH and extramural labs. We are working with Adam Phillippy’s lab (NHGRI) to identify viral sequences from hundreds of thousands of publicly available deep sequencing datasets, which has led to the discovery of a previously unknown human-associated polyomavirus. We are also collaborating with Karlyne Reilly of the Rare Tumor Initiative (NCI) and extramural colleagues to evaluate the extent that viruses may contribute to understudied tumor types. Lastly, we are collaborating with Jim DeCaprio (Dana Farber Cancer Center) to study the mechanisms of virally induced Merkel cell carcinoma.