Lucy S. Tompkins
Lucy S. Tompkins, Professor of Medicine (Infectious Diseases) and of Microbiology and Immunology
Clinical Microbiology H1537J,
Stanford University Medical Center Stanford, CA 94305-5402
Currently we are studying three bacterial species, including Legionella, Helicobacter, and Bartonella (Rochalimaea). The work on Legionella is focussed upon the role of a major secreted protein, a zinc metalloprotease, which we have shown to be involved in virulence in animals. Its role in modulation of the host immune defense is one important focus of this work. We have also identified Legionella genes that are regulated in response to intracellular growth. New molecular and genetic strategies are being used to identify other important determinants of pathogenesis involved in the interaction with eukaryotic cells.
Helicobacter pylori is a gastric spiral bacillus that causes gastritis, ulcers and gastric cancer. We have recently shown that adherence of H. pylori to gastric epithelial cells induces cytoskeletal rearrangements leading to pedestal formation. During attachment, eukaryotic proteins are phosphorylated, suggesting that H. pylori may influence signal transduction. Our current studies are focused on the cell biology mechanisms involved in this and other steps in pathogenesis.
In addition, we are searching for new genes involved in pathogenesis of infection and disease. Bartonella henselae is a newly discovered bacillus that causes cat scratch disease and bacillary angiomatosis. The pathological consequence of infection is dependent upon the host's immune status, since cat scratch disease occurs in those with normal immune mechanisms. Bacillary angiomatosis, a unique angiogenic response to infection, is a disease seen exclusively in those with impaired cellular immunity. We have identified bacterial genes that mediate attachment and invasion into eukaryotic cells, including endothelial cells and erythrocytes. We are investigating the genetic, molecular and cell biological aspects of pathogenesis of bartonellosis.
While most of the students in the laboratory study bacterial pathogenesis, some of them continue work in molecular and clinical epidemiology to study the natural history and outbreaks of infectious disease agents.
Dr. Tompkins' laboratory has a close functional relationship with Dr. Stanley Falkow's laboratory, and the students are co- mentored by both faculty members.
Black, W.J., F.D. Quinn and L.S. Tompkins. 1990. The Legionella pneumophila zinc metalloprotease is structurally and functionally homologous to Pseudomonas aeruginosa elastase. J. Bacteriol. 172:2608-13.
Relman, D.A., J.S. Loutit, T.M. Schmidt, S. Falkow and L.S. Tompkins. 1990. The agent of bacillary angiomatosis: an approach to the identification of uncultured pathogens. New Engl. J. Med. 323:1573- 80.
Moffat, J.F., P.H. Edelstein, D.P. Regula, Jr., and L.S. Tompkins. 1994. Effect of an isogenic zinc-metalloprotease deficient mutant of Legionella pneumophila in a guinea pig model and in Acanthamoeba. Molec. Microbiol. 12:693-706.
Cirillo J.D., S. Falkow, and L.S. Tompkins. 1994. Growth of Legionella pneumophila in Acanthamoeba castellanii. Infect. Immun. 62:3254-3261.
Segal, E, S. Falkow, and L.S. Tompkins. 1995. Helicobacter pylori attachment to epithelial cells induces cytoskeletal rearrangements and phosphorylation of host cell proteins. PNAS (submitted).
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