Role of microRNAs in the Pathogenesis of AIDS-NHL

Dharma Thapa, University of California Los Angeles
Advisor: Otoniel Martinez-Maza
Training in Basic Biomedical Sciences
Dissertation Award

The occurence of non-Hodgkin's lymphomas (NHL) in HIV infected individuals is an AIDS defining illness. Even in the post-HAART era, AIDS related non-Hodgkin's lymphoma (AIDS-NHL) remains a significant clinical problem. Recently, a lot of attention has been directed to the role of small non-coding microRNA (miRNA) in cancer, including NHL. miRNAs have been implicated in a variety of cellular processes regulating differentiation, proliferation, and apoptosis. Our working hypothesis is that a distinct pattern of miRNA expression will be seen in AIDS-NHL. Specifically, we aim to define the global miRNA expression signature in normal and malignant human B cell populations by using the multiplex Luminex bead-based profiling method; determine if miRNA expression signature exists in HIV infected individuals and whether malignancy associated miRNAs precede the development of AIDS-NHL; and finally, identify and verify the target genes for these malignancy associated miRNAs. Overall, this work may lead to identification of unique malignancy associated miRNAs in AIDS-NHL that would provide new information not only as a diagnostic marker, but could also be of prognostic significance and modulate current therapeutic approaches. Additionally, miRNA target studies could lead to identification of novel pathways that may play a role in the genesis and progression of AIDS-NHL.