MICaB Graduate Program
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B.S., University of Wisconsin, Madison, WI, 2011
Honors and Awards:
- NSF Graduate Research Fellowship, April 2014
- Travel award from NCI for DNA Tumor Virus Meeting, April 2015
- UMN COGS Travel Award, April 2016
As many as one in five cancers has a viral origin. For instance, nearly 100% of cervical cancers and 26% of head and neck squamous cell carcinomas (HNSCC) are due to infections by high-risk human papillomavirus (HPV). Interestingly, these cancers show upregulation of the antiviral DNA cytosine deaminase, APOBEC3B, which causes an increased proportion of cytosine mutations in 5’-TC motifs in the tumor genome. We recently showed that high-risk HPV induces the specific upregulation of APOBEC3B in keratinocytes. This raises the question—is the mutator phenotype caused by APOBEC3B upregulation required for virus-induced disease? My thesis research will determine if APOBEC3B upregulation is a more general property of DNA tumor viruses or an intrinsic characteristic of high-risk HPV. I will use both biochemical and bioinformatic methods to evaluate the effect of human polyomavirus infections and polyomavirus T antigens on the expression and activity of APOBEC3 enzymes. Additionally, I will observe how manipulation of APOBEC3 enzyme expression by these viruses and germline variants within the APOBEC locus impact associated diseases and any potential links with cancer development and progression. We anticipate that the results from these studies will provide valuable insights into these virus-host interactions and will provide novel pathways for targeted therapies to prevent disease.
- Lee YJ, Starrett GJ, Lee ST, Yang R, Henzler CM, Jameson SC, Hogquist KA. 2016. Lineage-Specific Effector Signatures of Invariant NKT Cells Are Shared amongst T, Innate Lymphoid, and Th Cells. J Immunol. 197:1460-1470.
- Verhalen B & Starrett GJ, Harris RS, Jiang M. 2016 Functional upregulation of the DNA cytosine deaminase APOBEC3B by polyomaviruses. J Virol. 90:14 6379-6386.
- Akre MK & Starrett GJ, Quist JS, Law EK, Temiz NA, Carpenter MA, Tutt AN, Grigoriadis A, Harris RS. 2016 Genome-wide view of APOBEC3B mutagenesis in human cells. PLOS One.
- Leonard B & Starrett GJ, Maurer MJ, Oberg AL, Helleman J, Berns EMJJ, Martens JWM, Anderson BA, Brown WB, Kalli KR, Kaufmann SH, Harris RS. 2016 APOBEC3G expression correlates with T cell infiltration and improved clinical outcomes in high-grade serous ovarian carcinoma. Clinical Cancer Research. 1078–0432.CCR–15–2910.
- Leonard B, McCann JL, Starrett GJ, Kosyakovsky L, Molan A, Brown WL, Harris RS. 2015 APOBEC3B upregulation by the PKC-NFKB pathway in multiple human cancers. Cancer Research. 10.1158/0008-5472.CAN-15-2171-T.
- Lee YJ, Wang H, Starrett GJ, Phuong V, Jameson SC, Hogquist KA. 2015 Tissue-specific distribution of iNKT cells impacts their cytokine response. Immunity. 43(3): 566-578.
- Swanton C, McGranahan N, Starrett GJ, Harris RS. 2015 APOBEC enzymes: Mutagenic fuel for cancer evolution and heterogeneity. (2015) Cancer Discovery. 5(7): 1–9.
- Vieira VC, Leonard B, White EA, Starrett GJ, Temiz NA, Lorenz LD, Lee D, Soares MA, Lambert PF, Howley PM, Harris RS. 2014. Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B. MBio 5(6):e02234-14.