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Dr. Russell assumed his position as Professor and Chair of the Department of Microbiology and Immunology in July 2000. He stepped down from his Chair's position in 2010 and now concentrates on his research work. 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:
VanderVen, B.C., Hermetter, A., Huang, A.Y., Maxfield, F.R., Russell, D.G. and Yates, R.M. (2010) Development of a novel, cell-based chemical screen to identify inhibitors of intraphagosomal lipolysis in macrophages. Cytometry A. 77:751-760. Kim, M-J., Wainwright, H. Locketz, M.L., Bekker, L-G., Walther, G.B., Maske, C., Dittrich, C., Visser, A., Wang, W., Hsu, F-F., Weichart, U., Tsenova, L., Kaplan, G., and Russell, D.G. (2010) Caseation of Human Tuberculosis Granulomas Correlates with Elevated Host Lipid Metabolism. EMBO Molecular Medicine. 2:258-274. Homolka, S., Niemann, S., Russell, D.G., and Rohde, K.H. (2010) Functional Genetic Diversity among M. tuberculosis Clinical Isolates: Delineation of Conserved Core and Lineage-Specific Transcriptomes during Intracellular Survival. PLoS Pathogens. 6(7):e100098. Seimon, T.A., Kim, M-J., Blumenthal, A., Koo, J., Ehrt, S., Wainwright, H., Bekker, L-G., Kaplan, G., Nathan, C., Tabas, I., and Russell, D.G. (2010) Induction of ER stress in macrophages of tuberculosis granulomas. PLoS One. 5(9):e12772. Russell, D.G., Barry, C.E., and Flynn, J. L. (2010) Tuberculosis: What we don’t know can, and does, hurt us. Science. 328:852-856. Russell, D.G., VanderVen, B.C., Lee, W., Abramovitch, R.B., Kim, M-J., Homolka, S., Niemann, S., and Rohde, K.H. (2010) Mycobacterium tuberculosis wears what it eats. Cell, Host, and Microbe. 8:68-76.
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