EBV-Positive Diffuse Large B-cell Lymphoma: Defining Biologic Determinants of Disease Pathogenesis in Immunodeficiency

University Of Vermont & St Agric College, Burlington VT

Investigators

Linked publications, trials & patents

Abstract

Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma (DLBCL) represents a clinically significant subtype often arising in immunodeficiency and defined viral latency states. Although proven in Western populations to confer worse outcomes and greater biologic aggression, the clinical impact and burden of disease for EBV(+) DLBCL is unknown, particularly in disparate immunodeficiency settings of endemic Human Immunodeficiency Virus (HIV) arising in sub-Saharan Africa (SSA) versus iatrogenic immunodeficiency in the United States (U.S.). Crucially, there is no diagnostic standard in defining EBV positivity in DLBCL, which is essential for the pathologic diagnosis and disease categorization. The lack of diagnostic and prognostic biomarkers of disease limits our understanding of EBV-mediated pathogenesis and the development of much-needed targeted therapies. The overall goal of this project will be to correlate the genomic biology of EBV(+) DLBCL to clinical variables of immunodeficiency and outcome to improve diagnostics, uncover pathogenic mechanisms, and identify potential therapeutic targets in global patient cohorts. The study will pursue two specific aims: 1) Define the EBV RNA and latency status of DLBCL in disparate immunodeficiency settings using an established global cohort from SSA and the U.S., 2) Global molecular profiling of EBV-associated DLBCL arising in immunodeficiency, using the established cohort. Outcomes from this study will advance our knowledge in EBV pathogenesis of DLBCL across immunodeficiencies, potentially identifying both diagnostic and prognostic biomarkers of disease and unveil therapeutic targets. With the COBRE support, Dr. Volaric will develop the necessary skills in bioinformatics data analysis and processing as well as global health project management and leadership that will position her optimally to establish an independent research program. Dr. Volaric has assembled strong mentorship and scientific advisory teams, led by her primary mentor Dr. Seth Frietze, with expertise in EBV-mediated lymphomagenesis, multi-omics analysis, multiplex imaging, bioinformatics, biostatistics, biorepository management, and development of global research partnerships. With the team’s guidance and mentorship, Dr. Volaric will develop and strengthen her scientific skillsets to emerge as a leader in global lymphoma research and collaborative partnerships.