Gabriel J. Starrett, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 37, Room 4128
- Bethesda, MD 20892-4263
Our group studies the contributions of tumor viruses, including polyomaviruses and papillomaviruses, to the development of cancer using sequencing, bioinformatics and classical wet bench molecular biology. Primarily, we are exploring the mechanisms through which these viruses trigger instability of the host cell genome that leads to integration of the viral genome and mutagenesis by APOBEC3 enzymes.
Areas of Expertise
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.
Polyomavirus T-Antigen Induces APOBEC3B Expression using a LXCXE-Dependent and TP53-Independent Mechanism
Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma
Gabriel J. Starrett, Ph.D.
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.
There are no open positions at this time. Check back again later, or take a look at CCR's Careers page.