Our laboratory is interested in the basic biology of lymphocytes and application of knowledge about lymphocytes to human disease. Much of our work concentrates on T cells and their peculiar ability, via their aß T cell receptors (TCRs), to react with foreign antigens when these are bound as peptides to major histocompatibility complex proteins (MHC) of the host. We are interested in the structural reasons for this bias, the role of evolution in creating the bias, and the ability of T cells to distinguish between different alleles of MHC proteins, an ability which affects the health of the host and rejection of transplants.
T cells not only protect against infection but also drive autoimmune and allergic diseases and, potentially, could play a role in rejection of cancers. Our laboratory studies the interactions between TCRs and their target antigens in these various conditions with the goal of understanding why autoimmune disease and allergies occur in only some individuals and of improving cancer vaccines. We would also like to improve the formulations of vaccines and study an adjuvant, alum, that is commonly used to increase the efficiency with which vaccines prevent diseases.
Finally in an effort to understand why some autoimmune diseases occur more frequently in women than men, we have recently described a population of B cells with unexpected properties that may account for some of this bias, both in humans and mice.
To accomplish these studies our laboratory collaborates extensively with others in the Department.
Bai X, Stitzel JA, Bai A, Zambrano CA, Phillips M, Marrack P and Chan ED. Nicotine impairs macrophage control of tuberculosis. Am J Respir Cell Mol Biol. In press 2017.
Rubtsova K, Rubtsov AV, Thurman JM, Mennona JM, Kappler JW and Marrack P. B cells expressing the transcription factor T-bet drive lupus-like immunity. J. Clin, Invest. 127:1392-1404, 2017. PMC 5373868.
Michels AW, Landry LG, McDaniel KA, Yu L, Campbell-Thompson M, Kwok WW, Jones KL, Gottlieb PA, Kappler JW, Tang Q, Roep BO, Atkinson MA, Mathews CE, Nakayama M. roinsulin-specific, HLA-DQ8, and HLA-DQ8-transdimer-restricted CD4+ T cells infiltrate islets in type 1 diabetes. Diabetes 66:722-734, 2017. PMC5319719.