Ph.D., Cornell University (Genetics)
Academic Rank: Professor
Phone: 314-977-9296 Fax: 314-977-8499
Primary Area of Cardiovascular Research Interest
-Pro-inflammatory immune effector cells, including natural killer (NK) cells and macrophages
Related Areas of Cardiovascular Research Interest
-Regulation of natural killer cell and macrophage activation by cytokines, pathogens and tumor cells
Summary of Cardiovascular Research Interest
My laboratory is working on the further characterization of natural killer lytic-associated molecule (NKLAM) and its role in immune function. NKLAM is a gene first cloned and identified in this laboratory. NKLAM protein is critical for tumor cell killing mediated by natural killer (NK) cells and cytotoxic T cells, and plays a role in phagocytosis mediated by macrophages. We have generated NKLAM-deficient mice, which have reduced NK and macrophage activity. We are now focusing on four main projects:
1) Define the role of NKLAM in NK cytotoxic function. We have identified NKLAM as an E3 ubiquitin ligase, an enzyme involved in ubiquitination of proteins, which results in their degradation. We are now testing the hypothesis that NKLAM, acting as an E3 ligase, enters tumor target cells upon NK-target cell interaction, where it ubiquitinates anti-apoptotic molecules, resulting in tumor cell death.
2) Test the hypothesis that NKLAM, by ubiquitinating proteins associated with phagosome maturation, results in enhanced bacterial death following phagocytosis. Killing of multiple bacteria, including E. coli and S. aureus, will be assessed.
3) Further characterize NK, T cell and macrophage activity in NKLAM-deficient mice. The ability of NKLAM-deficient mice to fight viral and bacterial infections and tumor challenges will be assessed.
4) NKLAM interacts with a novel protein, uridine cytidine kinase like-1 (UCKL-1). Our studies have shown that NKLAM ubiquitinates UCKL-1, leading to its degradation. Results suggest that UCKL-1 protects tumor cells from NK-mediated cytolysis. Studies are in progress to further assess the role of UCKL-1 in tumor survival and/or apoptosis.
In addition to these projects, my laboratory is collaborating with Dr. Jane McHowat to evaluate the role of iPLA2 in tumor cell metastasis in vivo.