Molecular Genetics and Microbiology

Project Title:Defining pathologic and genetic features of gammaherpesvirus-driven B cell lymphomas

Faculty Mentor’s Name:Dr. Scott Tibbetts

Research Project Description:

The human gammaherpesvirus Epstein-Barr virus (EBV) is a highly ubiquitous pathogens that is associated with the development of multiple types of B cell lymphomas, including diffuse large B cell lymphoma (DLBCL), Burkitt B cell lymphoma, and B cell primary effusion lymphoma (PEL). Previous studies carefully characterizing biopsies have provided insight into advanced EBV tumors. However, critical determinants of tumor initiation and progression are almost completely unknown due the lack of strict species specificity of these viruses and the lack of a well-defined animal model system for gammaherpesvirus tumorigenesis. Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of rodents that is genetically and pathogenically related to EBV. MHV68 infection of susceptible mice results in the development of B cell tumors with characteristics of large B cell lymphomas, providing the only means by which to study gammaherpesvirus tumorigenesis in the context of a natural host-virus system. However, at present this model is poorly defined. The specific goal of the work in this project will be to apply modern molecular and genetic technologies to define and subclassify MHV68 B cell lymphomas. To achieve this, we will (a) perform in situ staining for RNA and protein features of tumor sections, and (b) perform high throughput sequencing to define the mutational landscape of individual tumors. In conjunction with hematopathologist and bioinformatics collaborators, results will be directly compared to human B cell lymphoma data sets to facilitate tumor subclassification and to provide critical foundational data for future projects.

Entry Date:December 4, 2019