Faculty
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Gary D. Luker, M.D. |
Innate immunity and viral-host pathogenesis
Research in my laboratory focuses on understanding how interactions between "invaders", either DNA viruses or cancer cells, and the environment of a normal host affect disease pathogenesis. Because disease outcome is affected significantly by the integrated signaling pathways in an intact organism, we emphasize molecular imaging as a unique approach to identify and study key regulatory molecules in living mice.
We study effects of innate immunity on pathogenesis of Vaccinia virus, a DNA virus that expresses a wide variety of genes that counter the host immune response to infection. In particular, we are interested in mechanisms through which interferons and toll-like receptor signaling pathways affect viral replication and spread in the lung. This research uses recombinant reporter viruses and genetically-engineered mice, combining studies in living mice and cell culture models.
We also are studying functions of chemokines and chemokine receptor signaling in primary and metastatic cancer. Our current research focuses on the chemokine CXCL12 (also referred to as SDF-1) and its receptor CXCR4. This signaling pathway appears to regulate several steps in cancer initiation, progression, and metastases in many cancers, including breast and brain. We now are investigating regulation of CXCR4 signaling in mouse models of cancer with the goal of defining specific mechanisms through which CXCR4 promotes breast cancer.
Legionella pathogenesis
Legionella pneumophila, the causal agent of Legionnaires’ disease, is normally found in a variety of aquatic environments, most often as parasites of free-living unicellular organisms such as amoebae. Legionella that infect and are released from amoebae are more invasive and survive better in human macrophages, an essential step in the development of Legionnaires’ disease. Dr. Engleberg and his colleagues have found that L. pneumophila is more virulent in animals when inoculated together with amoebae. Studies are focused on determining the reason for the enhencement and establishing the role of amoebae in aerosols that infect humans.
Selected Publications:
Luker KE, Smith MCP, Luker GD, Gammon ST, Piwnica-Worms H, Piwnica-Worms D. Imaging regulated protein-protein interactions in cells and living animals by optimized luciferase protein fragment complementation. Proc Natl Acad Sci USA 2004; 101: 12288-12293.
Smith MCP, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D, Luker GD. CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res 2004; 64: 8604-8612.
Barreiro R, Luker GD, Herndon J, Ferguson TA. Termination of antigen-specific immunity by CD95 ligand (Fas ligand) and IL-10. J Immunol 2004; 173:1519-1525.
Luker GD , Prior JL, Song J, Pica CM, Leib DA. Bioluminescence imaging reveals systemic dissemination of HSV-1 in the absence of interferon receptors. J Virol 2003; 77: 11082-11093.
Krug A, Luker GD, Barchet W, Leib DA, Akira S, Colonna M. Herpes simplex virus type 1 (HSV-1) activates natural interferon-producing cells (IPC) through toll-like receptor 9. Blood 2003; 103: 1433-1437.
