ABSTRACT This Phase 2 renewal is premised upon the prior success of the “Center for Translational Viral Oncology” (CTVO) and upon evolving research themes that leverage new faculty expertise and health-disparate, cancer prone populations in our region. Virus-induced malignancies, such as human papilloma virus (HPV)-induced anogenital, and KSHV-associated Kaposi Sarcomas are highly prevalent in Louisiana and occur at increased incidence in people living with HIV. Given the regional need for viral cancer research, CTVO Phase 2 is essential to: 1) sustain the career development of talented Junior Principal Investigators (JPIs); 2) to support existing and coalescing research between regional scientists in viral oncology; and 3) to reinforce the institutionalization of productive core facilities. The overarching goal of CTVO is to improve disease management and quality of life across the diverse spectrum of Louisiana cancer patients through responsive research activity. Our immediate goal is to comprehensively prepare young investigators to conduct cutting edge viral oncology research and to better define how HIV co-infection predisposes many malignancies. As part of this goal CTVO will continue to reinforce collaborations between existing cancer virology and COBRE programs at LSU New Orleans, LSU Baton Rouge, LSU Shreveport, and Tulane University, to form a highly productive collaborative network, as part of the Louisiana IDeA Networks of Biomedical Research Excellence (INBRE). The CTVO will support the scientific, mentoring and administrative needs of the JPIs by providing (i) mentoring teams composed of NIH-funded basic science and clinical investigators dedicated to guiding JPI research project implementation and career development; (ii) unique clinical material consisting of annotated biospecimens collected from HIV+ and HIV- patients with virus-associated cancers at the University Medical Center, New Orleans; (iii) a supportive administrative core (ADMIN) to facilitate mentoring networking, career development, and critical external evaluation; (iv) dynamic research core facilities including the HIV clinical tumor biorepository (HCTB), a molecular histopathology/analytical microscopy core (MHAM), a cellular immunology/metabolomics core (CIMC), a translational genomics core (TGC), and a biostatistics and bioinformatics core (BBC), which were specifically designed to assist in state-of-the-art JPI research endeavors. CTVO focuses this structure on four JPI-led research projects that 1) study HIV-1's impact on immune reprogramming to predispose neoplasia, 2) seek to define the molecular underpinnings of Kaposi's Sarcoma- associated herpesvirus (KSHV) latency and tumorigenesis, 3) investigate interactions between human papilloma virus (HPV) and Epstein–Bar virus (EBV) in anogenital cancer, and 4) test relationships between human endogenous retroviral (HERV) expression and glioblastoma stemness and drug resistance. Finally, a pilot research program wi...