We primarily use mouse-models to study the regulatory processes controlling successful and unsuccessful immune responses. We breed numerous genetically engineered mice that help us to dissect specific aspects of the immune response. Much of our work relies on in vivo and ex vivo analyses tools such as multiparameter flow cytometry for functional and phenotypic studies, histology and immunohistochemistry, ELISA, ELISPOT, Laser-dissection microscopy, microarray/RNAseq and qRT-PCR analysis and other state-of-the-art cellular and molecular immunological assays.
Our studies are conducted in collaboration with Drs. Stephen Barthold (CCM, UC Davis), Scott Simon (UC Davis, Biomedical Engineering), Frances Lund, Troy Randall and Allan Zajac (University of Alabama, Birmingham) and Eun-Frances Lee and Inaki Sanz (Emory University). We also work with Northrup Gruman and the J. Craig Venter Institute to enhance the utility of the Influenza Research Database (www.fludb.org), a NIH-supported web-based database for influenza research.
We use two mouse infectious disease models for our studies: Infections with influenza virus and infections with Borrelia burgdorferi, a bacterial spirochete and the causative agent of Lyme disease. The influenza infection models serve as an outstanding example of a highly successful B cell response, which we can use to identify the innate and adaptive immune regulators that control the induction and maintenance of highly protective responses. In contrast, following infection with Borrelia burgdorferi, an immune response is induced, but the bacteria cannot be cleared. We find great abnormalities in the B cell response, most importantly, a lack of long-term adaptive immunity. We hope to understand the reasons for this lack of long-term immune induction. Furthermore, we are probing the CD4 T cell responses to this pathogen to determine whether these responses are also affected.
Innate-like B cells
While T and B cells are a central part of the adaptive immune system, a small subset of B cells, termed B-1 cells, is considered an “innate-like” lymphocyte, because it expresses aspects of the adaptive immune system (an antigen-receptor that relies of gene-rearrangement) and the innate immune system (rapid responses to innate signals, a BCR that responds to pathogen-associated molecular patterns). These cells contribute nearly all of the protective natural IgM antibodies that are constitutively generated in mice, independent of whether the mice were infected or not, or whether they were colonized with bacteria in their gut and on mucosal surfaces, or are held under sterile conditions. We are interested in identifying the mechanisms by which these B cells generate antibodies without stimulation by foreign antigens. We are also interested in identifying the functions of IgM during influenza infection and during infection with B. burgdorferi that are unique to this type of antibodies by their interaction with specific IgM-recognizing receptors.
Graduate Student (DVM/PhD dual degree)