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Dr. Russell assumed his position as Professor and Chair of the Department of Microbiology and Immunology in July 2000. His previous experience was as professor in the Department of Molecular Microbiology at Washington University School of Medicine, in St. Louis, where he had worked since 1990. He received a B.Sc. degree in Zoology from St. Andrews University in Scotland in 1979 and was awarded a Ph.D. from Imperial College, London University in 1982. He has held positions at the University of Kent, the Max-Planck-Institute in Tuebingen, and NYU School of Medicine prior to moving to St. Louis. His research program has maintained continuous funding from the National Institutes of Health for research into the biology of the intramacrophage pathogens Mycobacterium and Leishmania. Research Interests | Graduate Fields | Lab Members | Related Links | Selected References Mycobacterial species are important pathogens of both animals and humans. Study into the lifestyles of these pathogens reveals extensive parallels in their mechanisms of intracellular survival and persistence. Our lab is dedicated to the study of pathogenic mycobacteria and the main goals of the work in the lab fall into three discrete areas of research addressing the interaction between the macrophage and the bacterium with respect to the intracellular environment and the regulation of host cell function. Firstly, the intracellular vacuole in which the bacillus resides exhibits arrested maturation and fails to differentiate into acidic, hydrolytically-active lysosomes. We are actively pursuing both the mechanism and consequences of this unusual strategy for intracellular survival. If the macrophage is activated, the host cell can overcome this blockage and deliver the bacterium to a lysosomal compartment, culminating ultimately in the death of the bacterium. We are studying the effects that macrophage activation has on intracellular trafficking using new assays that quantify phagosome/lysosome fusion and the hydrolytic capacity of the evolving environment within the lumen of the vacuole. These studies address basic questions with respect to the regulation and progression of phagosome maturation. Secondly, studies on carbon source utilization by intracellular Mycobacterium demonstrate that the bacterium needs to metabolize fatty acids when the course of infection changes from the acute phase to the chronic phase, and the bacterium transitions into a more vegetative growth cycle. We are exploiting genetic approaches to identify genes involved in uptake and breakdown of host fatty acids. The enzymes of this pathway are being pursued as drug targets. In pursuit of this goal we have developed microarray approaches to define the metabolic status of the bacterium in its intracellular niches at differing levels of macrophage activation. Finally, mycobacterial infections induce formation of granulomas that
prevent spread of infection yet in turn provide a safe haven for the bacterium
because they retain the lymphocytes of the host at a distance from the
infected macrophages. The bacterial cell wall constituents are released
by intracellular organisms and appear to promote formation of the granuloma.
We have developed an in vitro model system to determine the cytokine and
chemokine pathways activated in formation and maintenance of this structure.
The role(s) of these lipids in guiding the progress of the infection is
being studied and the findings of this in vitro model are being examined
in the context of human tuberculosis.
Dr. Russell is a member of the following Graduate Fields:
Program in Infection and Pathobiology VanderVen, B.C., R.M. Yates, and D.G. Russell. (2009). Intraphagosomal measurement of the magnitude and duration of the oxidative response. Traffic. 10:372-378. Hagedorn, M., K.H. Rohde, D.G. Russell, and T. Soldati. (2009). Infection by tubercular mycobacteria is spread by non-lytic ejection from their amoeba hosts. Science. 323:1723-1729. Bowdish, D.M.E., K. Sakamoto, S. Mukhopadhyay, C.A. Leifer, K. Tryggvason, S. Gordon, and D.G. Russell. (2009). MARCO, TLR2, and CD14 form a functional receptor complex for mycobacterial trehalose 6,6’-dimycolate. PLoS Pathogens. 5:e1000474. Russell, D.G., B.C. Vanderven, S. Glennie, H. Mwandumba and R.S. Heyderman. (2009). The macrophage marches on its phagosome: Dynamic assays of phagosome function. Nat Rev Immunol. 9:594-600. Purdy, G.E., M. Niederweis, D.G. Russell. (2009). Decreased outer membrane permeability protects mycobacteria from killing by ubiquitin-derived peptides. Mol Microbiol. 73:844-857. Russell, D.G., P-J. Cardona, M-J. Kim, S. Allain, and F. Altare. (2009). Foamy macrophages and the progression of the human tuberculous granuloma. Nature Immunol. 10:943-948.
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