SVM: Pathology, Microbiology & Immunology
Center for Comparative Medicine
California National Primate Research Center
University of California, Davis
Research Interest: Our lab's primary research interests center around delineating immunological and molecular mechanisms of CD4 T cell help. Our ultimate goal is to use this information to design an effective HIV vaccine and in parallel understand mechanisms of HIV susceptibility and pathogenesis.
Harnessing TFH cells for HIV vaccine design
Our first goal is to figure out the fundamental cues necessary for inducing effective CD4 T follicular helper cell (TFH) responses in order to generate long-lived anti-HIV antibody. TFH cells are a subset of CD4 T cells that aid B cells in navigating and enduring the unforgiving environment of the germinal center (GC). With help from TFH cells, GC B cells can differentiate to plasma cells which are the source of long-lived antibody - central to the success of the majority of licensed vaccines. Clearly, generating a strong TFH and GC response is a pre-requisite of an effective HIV vaccine. But there is another layer of complexity to grapple with. As it turns out, akin to CD4 T cells, TFH cells skew towards different helper profiles. What we don't clearly understand is which TFH profile favors the induction of persistent and broadly neutralizing anti-HIV antibodies. One of the projects in the lab tackles this question applying cutting edge immunological approaches using the non-human primate model.
Outsmarting HIV target cells
Our second research goal is to figure out immune attributes of HIV susceptibility with a primary focus on CD4 target cells in the genital and rectal mucosa. The genital and rectal mucosal surfaces constitute the major portal of HIV transmission and yet we know very little about target cells in this compartment. In collaboration with clinicians, our goal is to understand how vaccination modulates the immune environment of the mucosa and whether certain attributes render CD4 T cells more vulnerable to HIV entry. By identifying these highly susceptible CD4 T cells, we can design more effective strategies to prevent HIV infection.