I have a long-standing interest in host/pathogen interactions and their impact human health. My lab investigates Epstein-Barr virus (EBV) pathogenesis and related B-cell immunobiology. My undergraduate research with Stanley Falkow at Stanford provided a foundation in molecular genetics and microbial pathogenesis. Intrigued by how human cytomegalovirus (HCMV) evades immune responses, I focused my Harvard Immunology thesis with Hidde Ploegh and Don Wiley on HCMV-encoded US2 subversion of MHC antigen presentation. Our crystal structure of the US2/HLA-A2 complex provided the first molecular view of virus down-modulation of MHC class I, a hallmark of viruses that establish lifelong infection. During my clinical training at Harvard Medical School, I became intrigued by the link between Epstein-Barr virus (EBV) and multiple cancers. My post-doctoral studies with Elliott Kieff studied how EBV oncoprotein LMP1 mimics the key B-cell co-receptor, CD40 to activate NF-kB pathways.
My laboratory uses systematic genetic, proteomic and metabolomic approaches to investigate the EBV/host relationship. We use large-scale CRISPR genetic analysis to study EBV host/pathogen interactions, including epigenetic factors that control viral genome programs and EBV-induced dependencies that can be targeted therapeutically. We use ChIP-seq, RNAseq and mass spectrometry approaches to identify how EBV transforms human B-cells into immortalized lymphoblasts, and how this process differs from B-cell responses to prototypic immune receptor stimuli. Similarly, we use proteomic approaches to characterize how EBV rewires B-cells upon lytic reactivation, where infectious viral particles are produced. We also study novel human primary immunodeficiencies manifest by susceptibility to EBV and EBV-associated malignancies.
I am an Assistant Professor of Medicine at the Brigham & Women’s Hospital and the Associate Chair of the Harvard Medical School Graduate Program in Virology. I attend on the Infectious Disease transplant oncology service, where I am reminded of the unmet clinical needs and have opportunities for bedside to bench research.