Kaposi's sarcoma-associated virus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KS is a highly angiogenic tumor that is driven by KSHV-infected endothelial cells, and KS lesions express high levels of cytokines and angiogenic growth factors. We have found that latent KSHV infection dramatically alters angiogenesis, migration, and survival of endothelial cells. Latent KSHV infection of endothelial cells results in the upregulation of multiple cytokines and chemokines. We hypothesize that the upregulated cytokines and chemokines play important roles in driving angiogenesis and cell proliferation of KSHV-infected cells, and we propose to determine the mechanism by which these factors regulate cell growth, survival, and angiogenesis. We will also determine how KSHV infection affects cell migration. Finally, we have identified cellular and viral proteins that modulate the ubiquitin pathway. Hence, we propose to determine how these factors alter cellular ubiquitination pathways, to promote cell migration and survival of the infected cell. In summary, we propose to analyze the biological pathways that are altered upon KSHV infection of endothelial cells in order to understand the mechanism of KSHV-mediated oncogenesis. We hypothesize that the modulation of cell migration, angiogenesis and anti-apoptotic pathways by KSHV promotes tumorigenesis and contributes to the pathogenesis associated with KSHV infection. Thus, the proposed studies will provide significant and biologically relevant insights into KSHV biology, and will also identify new targets for future therapies against KSHV-associated cancers.
KSHV is a human pathogen associated with three different human cancer. Hence it is important to understand how KSHV establishes life-long latency in its host and the mechanisms by which KSHV promotes tumorigenesis.
|Eason, Anthony B; Sin, Sang-Hoon; Lin, Carolina et al. (2016) Differential IgM expression distinguishes two types of pediatric Burkitt lymphoma in mouse and human. Oncotarget 7:63504-63513|
|El-Mallawany, Nader Kim; Kamiyango, William; Slone, Jeremy S et al. (2016) Clinical Factors Associated with Long-Term Complete Remission versus Poor Response to Chemotherapy in HIV-Infected Children and Adolescents with Kaposi Sarcoma Receiving Bleomycin and Vincristine: A Retrospective Observational Study. PLoS One 11:e0153335|
|Schifano, Jason M; Corcoran, Kathleen; Kelkar, Hemant et al. (2016) Expression of the Antisense-to-Latency Transcript Long Noncoding RNA in Kaposi's Sarcoma-Associated Herpesvirus. J Virol :|
|Sin, Sang-Hoon; Kang, Sun Ah; Kim, Yongbaek et al. (2016) Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Compensates for Interleukin-6 in Initial B Cell Activation. J Virol 90:2150-4|
|Westmoreland, Katherine D; Stanley, Christopher C; Montgomery, Nathan D et al. (2016) Hodgkin lymphoma, HIV, and Epstein-Barr virus in Malawi: Longitudinal results from the Kamuzu Central Hospital Lymphoma study. Pediatr Blood Cancer :|
|Dittmer, Dirk P; Damania, Blossom (2016) Kaposi sarcoma-associated herpesvirus: immunobiology, oncogenesis, and therapy. J Clin Invest 126:3165-75|
|Ma, Zhe; Damania, Blossom (2016) The cGAS-STING Defense Pathway and Its Counteraction by Viruses. Cell Host Microbe 19:150-8|
|Bhatt, Aadra Prashant; Wong, Jason P; Weinberg, Marc S et al. (2016) A viral kinase mimics S6 kinase to enhance cell proliferation. Proc Natl Acad Sci U S A 113:7876-81|
|Damania, Blossom (2016) A Virological Perspective on Cancer. PLoS Pathog 12:e1005326|
|Bermek, Oya; Willcox, Smaranda; Griffith, Jack D (2015) DNA replication catalyzed by herpes simplex virus type 1 proteins reveals trombone loops at the fork. J Biol Chem 290:2539-45|
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