4:30 PM Keynote Address II Blossom Damania Shannon Hall
Blossom Damania is the Boshamer Distinguished Professor and Vice Dean for Research in the School of Medicine at the University of North Carolina at Chapel Hill (UNC-Chapel Hill). She is a professor in the Department of Microbiology & Immunology and is a member of the Lineberger Comprehensive Cancer Center at UNC-Chapel Hill. She obtained her B.A. from Mount Holyoke College in 1992 and her PhD from the Cell & Molecular Biology program at the University of Pennsylvania in 1998. She was a postdoctoral fellow at Harvard Medical School prior to joining the faculty at UNC-Chapel Hill in 2000. For her work, Dr. Damania has received several honors including being named a V Foundation for Cancer Research Scholar, an AACR Gertrude B. Elion Research Scholar, a Burroughs Welcome Investigator in the Pathogenesis of Infectious Disease, and a Leukemia & Lymphoma Society Scholar. She is a Fellow of the American Academy of Microbiology and the American Association for the Advancement of Science. She received the Dolph O. Adams award from the Society for Leukocyte Biology and was also named a Kavli Fellow by the National Academy of Sciences, USA.
Dr. Damania’s research focuses on oncogenic human herpesviruses and host-pathogen interactions. She uses a multi-faceted approach towards understanding host innate immune responses to viral infection, as well as viral oncogenesis. Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, and two lymphoproliferative diseases, primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). Moreover, KSHV is the causative agent of KS-immune reconstitution syndrome (KS-IRIS) and KSHV-inflammatory cytokine syndrome (KICS). KSHV promotes tumorigenesis by modulating cell signaling networks, enhancing angiogenesis, and evading immune sensing pathways. Understanding the mechanisms by which KSHV manipulates cellular pathways will allow us to identify targets for future therapeutics again KSHV-associated viral cancers.
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PLoS Pathog. 2018 Sep 13;14(9):e1007267. doi: 10.1371/journal.ppat.1007267. eCollection 2018 Sep.
Chromatin remodeling controls Kaposi’s sarcoma-associated herpesvirus reactivation from latency.
Hopcraft SE1, Pattenden SG2, James LI2, Frye S2, Dittmer DP1, Damania B1.
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Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of three human malignancies, the endothelial cell cancer Kaposi’s sarcoma, and two B cell cancers, Primary Effusion Lymphoma and multicentric Castleman’s disease. KSHV has latent and lytic phases of the viral life cycle, and while both contribute to viral pathogenesis, lytic proteins contribute to KSHV-mediated oncogenesis. Reactivation from latency is driven by the KSHV lytic gene transactivator RTA, and RTA transcription is controlled by epigenetic modifications. To identify host chromatin-modifying proteins that are involved in the latent to lytic transition, we screened a panel of inhibitors that target epigenetic regulatory proteins for their ability to stimulate KSHV reactivation. We found several novel regulators of viral reactivation: an inhibitor of Bmi1, PTC-209, two additional histone deacetylase inhibitors, Romidepsin and Panobinostat, and the bromodomain inhibitor (+)-JQ1. All of these compounds stimulate lytic gene expression, viral genome replication, and release of infectious virions. Treatment with Romidepsin, Panobinostat, and PTC-209 induces histone modifications at the RTA promoter, and results in nucleosome depletion at this locus. Finally, silencing Bmi1 induces KSHV reactivation, indicating that Bmi1, a member of the Polycomb repressive complex 1, is critical for maintaining KSHV latency.
PMID: 30212584