Research Interests

Immune response to Chlamydia trachomatis (Ct) and Host-Pathogen Interaction

The obligate intracellular bacteria, Chlamydia Trachomatis is the leading cause of bacterial sexually transmitted infection worldwide and of preventable blindness worldwide. The organism infects epithelial cells as a highly infectious elementary body (EB), creates an inclusion membrane around itself forming a vacuole, and converts to a metabolically active reticulate body (RB) which multiples within the inclusion.

Chlamydiae have lost the genetic material other bacteria require for extracellular growth and instead have acquired genes that enhance their intracellular survival including blocking immune response. A major host response is mediated by interferon gamma (IFN-g). We found that the guanylate binding protein GBP-1, a GTPase, has anti-Ct activity and represents a major effector of the INF-g induced host cell response. We hypothesize that Ct secretes a virulence-related protein across the inclusion membrane into the host cytosol to block the effect of GBP-1. The mechanism of this host-pathogen response is under investigation.

Natural killer T (NKT) cells respond to Chlamydia infected cells and influence the adaptive T cell response. We are studying the NKT response to Ct infected cells. We are also identifying potential Ct vaccine candidates. We identified T cells in the blood of infected individuals that respond to a Ct inclusion membrane protein called IncA.

The T cell Co-Receptor CD8

CD8 marks a subset of T cells that can kill cells infected with a pathogen as well as tumor cells. CD8 functions as a co-receptor with the T cell receptor (TCR), by binding to MHC class I with a foreign peptide forming a trimolecular complex. Using a combination of mutational and NMR analysis we are identifying contact regions and critical amino acids for CD8-MHC interaction. Our goal is to design a modified CD8 molecule with enhanced co-receptor function that can be added to anti-tumor killer T cells to increase their efficacy for tumor immunotherapy. In addition, the human CD8B gene is alternatively spliced, generating membrane-associated isoforms with different cytoplasmic tails. We found differences in expression pattern of these isoforms and are currently investigating their functional significance.