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.
Dr. Starrett received his bachelor’s degree in medical microbiology and immunology from the University of Wisconsin—Madison. He then earned a Ph.D. from the Microbiology, Immunology, and Cancer Biology program at the University of Minnesota—Twin Cities where he was a recipient of the National Science Foundation Graduate Research Fellowship. His thesis work in the lab of Reuben Harris, Ph.D., focused on the functional overlap of APOBEC3 enzymes in cancer and antiviral immunity, especially regarding polyomaviruses. During his graduate career, he received several awards including the MICaB Outstanding Graduate Student Award and the Milne & Brandenburg Award for exceptional research. He did his postdoctoral fellowship with Christopher Buck, Ph.D., Senior Investigator in CCR’s Laboratory of Cellular Oncology, where he studied the genetics of small and mid-sized DNA viruses from various environmental and disease sources. In 2019, Dr. Starrett was selected as the inaugural NIH Independent Research Scholar, and in 2021 he started as a Stadtman Tenure-Track Investigator in the Laboratory of Cellular Oncology.
- Starrett GJ, Thakuria M, Chen T, Marcelus C, Cheng J, Nomburg J, Thorner AR, Slevin MK, Powers W, Burns RT, Perry C, Piris A, Kuo FC, Rabinowits G, Giobbie-Hurder A, MacConaill LE, DeCaprio JA. Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma. Genome Med. 2020;12(1):30.
- Slevin MK, Wollison BM, Powers W, Burns RT, Patel N, Ducar MD, Starrett GJ, Garcia EP, Manning DK, Cheng J, Hanna GJ, Kaye KM, Van Hummelen P, Nag A, Thorner AR, DeCaprio JA, MacConaill LE. ViroPanel: Hybrid Capture and Massively Parallel Sequencing for Simultaneous Detection and Profiling of Oncogenic Virus Infection and Tumor Genome. J Mol Diagn. 2020;22(4):476-487.
- Tisza MJ, Pastrana DV, Welch NL, Stewart B, Peretti A, Starrett GJ, Pang YS, Krishnamurthy SR, Pesavento PA, McDermott DH, Murphy PM, Whited JL, Miller B, Brenchley J, Rosshart SP, Rehermann B, Doorbar J, Ta'ala BA, Pletnikova O, Troncoso JC, Resnick SM, Bolduc B, Sullivan MB, Varsani A, Segall AM, Buck CB. Discovery of several thousand highly diverse circular DNA viruses. Elife. 2020;9.
- Ondov BD, Starrett GJ, Sappington A, Kostic A, Koren S, Buck CB, Phillippy AM. Mash Screen: high-throughput sequence containment estimation for genome discovery. Genome Biol. 2019;20(1):232.
- Starrett GJ, Buck CB. The case for BK polyomavirus as a cause of bladder cancer. Curr Opin Virol. 2019;39:8-15.
Related Scientific Focus Areas
Genetics and Genomics
Microbiology and Infectious Diseases
This page was last updated on Tuesday, September 20, 2022