Gabriel J. Starrett, Ph.D.
Our group primarily studies the contributions of tumor viruses, including polyomaviruses and papillomaviruses, to the development of cancer using both bioinformatics and classical wet bench molecular biology. A current focus of our work is on transplant recipients, who are at an increased risk of developing a variety of cancers. We are exploring the mechanisms through which viruses trigger instability of the host cell genome through integration of the viral genome and through induction of the mutagenic enzyme APOBEC3B.
1) polyomavirus, 2) papillomavirus, 3) cancer biology, 4) bioinformatics,
Our major projects make use of high-throughput sequencing to discover viruses in various disease states. Polyomaviruses and papillomaviruses are ubiquitous non-enveloped DNA viruses that can cause cancer in humans. I have previously found that 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 also showed evidence for acute APOBEC3 mutagenesis of the viral genomes present in kidney transplant recipients suffering from BK polyomavirus-associated nephropathy.
Kidney transplant recipients are also 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 Dr. Eric Engels and others, we are studying the genomic and transcriptomic features of bladder cancer and how these correspond to the presence of DNA tumor viruses.
Our group enjoys an extensive range of collaborations with other NIH and extramural labs. For instance, we have been 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 genomic characteristics of virus-positive and virus-negative Merkel cell carcinoma and potential impacts on patient outcome.
View Dr. Starrett's Google Scholar Profile.
Selected Recent Publications
- Journal of Virology. 90: 6379-6386, 2016. [ Journal Article ]
Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma.mBio. 8: e02079-16, 2017. [ Journal Article ]
Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in During In-Host Virus Evolution.Cell Host and Microbe. 23(5): 628-635, 2018. [ Journal Article ]
Polyomavirus T-Antigen Induces APOBEC3B Expression using a LXCXE-Dependent and TP53-Independent Mechanism.mBio. 10: e02690-18, 2019. [ Journal Article ]
Dr. Starrett received his B.S. 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 Dr. Reuben Harris focused on the functional overlap of APOBEC3 enzymes in cancer and antiviral immunity, especially in regard to polyomaviruses. During his graduate career he received several awards including the MICaB Outstanding Graduate Student Award and the Milne & Brandenburg Award for exceptional research by graduate students. He then did a postdoctoral fellowship in the Laboratory of Cellular Oncology, where he studied the genetics of polyomaviruses and papillomaviruses in various disease states. In 2019, Dr. Starrett was selected for the inaugural year of the NIH Independent Research Scholar Program, in which he is presently serving.
|Mary L. Piaskowski||Postbaccalaureate Fellow (CRTA)|