October 18, 2018
HPV researcher to present Oct. 19 Division of Biology seminar
Dohun Pyeon, associate professor of microbiology and molecular genetics at Michigan State University, will present "Immune Dysregulation and Cancer Progression Driven by Human Papillomavirus" as part of the Division of Biology Seminar Series at 4 p.m. Friday, Oct. 19, in 221 Ackert Hall.
Pyeon will talk about human papillomaviruses that are causally linked to more than 5 percent of all human cancers, including nearly all cervical cancer (CxCa) and approximately 25 percent of head and neck cancer, resulting in half a million deaths every year. FDA-approved prophylactic HPV vaccines effectively prevent infections by several high-risk HPV types. However, these vaccines do not cover all high-risk HPVs and lack therapeutic effects and will not impact existing HPV infections that may lead to invasive cancer for decades into the future. Therefore, there remains an urgent need to develop new tools for treating HPV-infected individuals and preventing HPV-associated cancers.
Since HPV modulates various host factors, they hypothesize that immune dysregulation by HPV contributes to immune suppression essential for virus persistence and cancer progression. To test the hypothesis, Pyeon's laboratory has established combined approaches with a novel HPV production system, in vitro keratinocyte culture systems, and in vivo mouse models that recapitulate HPV infection and tumor development. Additionally, they have performed transcriptome and methylome analyses of patient tissue specimens in different disease stages — normal, early and late precancers, and cancer.
Pyeon's research revealed that various interferon-inducible proteins and chemokines modulate HPV infection, persistence, and associated cancer progression. Notably, the cytidine deaminase APOBEC3A, stabilized by the HPV oncoprotein E7, functions as a restriction factor against HPV infection and contributes to somatic mutagenesis for cancer progression. They further uncovered that APOBEC3A has driven papillomavirus coevolution with their host species by selecting for variants that contain reduced APOBEC3A target sites in their genomes. We also found that HPV16 E7 suppresses antitumor immunity through epigenetic downregulation of the chemokine CXCL14. Restoration of CXCL14 expression in HPV-infected head and neck cancer cells suppresses tumor growth in a CD8+ T cell dependent manner. These findings provide novel mechanisms by which HPV establishes persistent infection and drives cancer progression. Their continuing studies will lead to better understanding of virus-induced immune suppression and developing new methods for cancer prevention and immunotherapies.
If you would like to visit with Pyeon, please contact Nick Wallace at firstname.lastname@example.org.