My laboratory focuses on several aspects of T cell and inflammation biology. Our aim is to uncover how T cells function so that we can guide and control behavior of these important immune cells. We believe that the outcome of this work will foster vaccine development, but also devise new ways to control unwanted immune responses. Our approach is to understand how adjuvants and costimulatory pathways influence the function of T cells, and define how cytokine networks impact immune cell behavior. A brief overview highlighting our goals are given below:

Vaccine Adjuvants: Commonly, vaccines are made up of antigen (Ag) and adjuvant. Antigens stimulate specific T and B cells through an Ag receptor, while adjuvants activate innate immune cells by triggering pattern recognition receptors. Without adjuvants vaccines would likely be ineffective. My lab studies several different adjuvants and one example is bacterial lipopolysaccharide, which stimulates innate immune cells such as macrophages through toll-like receptor-4 (TLR4). What’s striking is that the response emanating from TLR4 conditions Ag-stimulated T cells to survive. While the mechanism is largely unknown, our recent data suggest that a specific signaling pathway is key to survival. A goal is to uncover this process by using cellular approaches, biochemistry and proteomics.

T cell Costimulation: Costimulation of T cells provides an “on” signal that induces T cell growth, cytokine secretion, and programs survival and cytotoxic potential. Several years ago we discovered that a combination of costimulators fostered enhanced responses and reasoned that this combination would be useful in cancer treatment. In a collaborative study with Dr. Adam Adler (Department of Immunology, UCHC) and others, we tested this idea. Our recent data show that costimulating T cells through CD134 and CD137 induces both CD4 and CD8 T cells to become powerful effectors capable of killing tumor cells. This project is focused on understanding the mechanism of heightened T cell responsiveness with a goal of developing this approach for future use in cancer patients.

Pediatric Intestinal Inflammatory Diseases: A new collaborative research project with Dr. Francisco Sylvester, a pediatric gastroenterologist currently at The University of North Carolina at Chapel Hill (Chapel Hill, NC), is focused on studying the basis of ulcerative colitis, Crohn disease, and eosinophilic esophagitis in pediatric patients. This effort is comprised of a research team including clinicians and bioinformatics specialists that hope to bring basic observations from the clinic to the laboratory and back to the bedside. One idea we are working on is that specific cytokine networks determine disease state and severity. We believe that these cytokines networks are derived from changes in the microbiome of patients or byproducts of microbes, and postulate that understanding this process will help to develop new ways to divert active disease into remission.

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