Current Research and Scholarly Interests
T lymphocytes play a central role in the adaptive immune response. Understanding the biology of the response of T cells to immune challenge shoudl allow the development of new diagnostics and therapeutics to treat human disease. Research in my group is focuses on three areas:
1. Granulysin, a small molecule expressed by activated T cells and NK cells, lyses tumors and a variety of pathogens, including bacteria, fungi, and parasites. We have shown that synthetic peptides corresponding to linear regions of granulysin can recapitulate the lytic activity of the intact molecule. Substitution of critical residues resulted in mutant peptides that lyse pathogens but do not kill mammalian cells. We are currently developing granulysin derivatives as a new type of antibiotic as well as studying the mechanisms involved in granulysin induced cell death.
2. Tuberculosis kills more than 3,000,000 people each year. However, little is understood about the immune response to Mycobacterium tuberculosis, the bacterium that causes the disease. We are characterizing the immune response to individual antigens from Mycobacterium tuberculosis in lymphocytes from individuals with disease or who have been infected with Mycobacterium tuberculosis but do not develop tuberculosis. Correlates of protective immunity are critical to the development of an improved vaccine for tuberculosis.
3. Lymphotactin is a chemokine that is expressed in both activated and anergic T cells. Lymphocytes treated with lymphotactin are refractory to stimulation, suggesting that lymphotactin may be used to induce tolerance in vivo. Studies are ongoing to define the role of lymphotactin in the immune response in vitro and in vivo and to use this information to develop new tolerance inducing modalities.
