Professor, Department of Pathology, Division of Medical Microbiology
The Johns Hopkins Hospital
Department of Pathology
Division of Microbiology
Ross 624
720 Rutland Avenue
Baltimore, MD 21205
Phone: (410) 614?4862
Lab: (410) 955?8654
Fax: (443) 287?3665
Email: sdumler@jhmi.edu
sdumler@jhmi.edu
Phone
(410) 955-8654
J. Stephen Dumler, M.D.
Primary Appointment in Pathology; Joint Appointment in Molecular Microbiology & Immunology (BSPH)
Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Molecular Microbiology and Immunology (BSPH); Member, Graduate Program in Pathobiology
Molecular microbiology has been incredibly successful identifying novel and emerging infectious agents and in elucidating their pathogenetic mechanisms. We have used a multi-disciplinary approach with molecular, immunologic, pathologic, genomic, and microbiologic methods to study tick-borne diseases and obligate intracellular bacteria.
As a result, we discovered a previously unknown human tick-borne infection, now called human granulocytic anaplasmosis (HGA), which is caused by Anaplasma phagocytophilum, an obligate intracellular rickettsia-like bacterium that infects neutrophils. My laboratory's current research centers upon dissecting the molecular and host immunologic mechanisms and ecologic conditions that lead to significant human morbidity with infection by these agents and concurrently transmitted tick-borne pathogens such as Borrelia burgdorferi.
There are three major avenues of research in my laboratory: i) inflammatory and immunopathological mechanisms in human anaplasmosis - how does A. phagocytohilum induce inflammation and immune reactions that are the principle basis of disease? ii) interactions of A. phagocytohilum with neutrophils - how does this micro-organism change normal neutrophil function to allow pathogen survival, and what are the effects of neutrophil changes in pathogenesis at the cellular and molecular levels? iii) how do changes in A. phagocytophilum-infected neutrophils affect the ability of co-transmitted pathogens, such as Borrelia burgdorferi to cause disease?
We are studying the fundamental effects of A. phagocytophilum gene products on neutrophils, with particular attention to major surface protein (Msp)-2 family that appear to be adhesions, and to AnkA, that apparently is secreted from the bacterium and transported into the host nucleus to interact with the heterochromatin at matrix attachment regions, perhaps influencing global gene transcription. We also developed animal models of human anaplasmosis that mimic disease in an effort to study our in vitro correlates of pathogenesis in an in vivo situation.
The Medical Microbiology Laboratory is also interested in the application of molecular microbiologic methods as new approaches to diagnose infectious diseases. This is accomplished by identification of fastidious, slow growing, and non-cultivable agents or identification of important virulence factor genes by a variety of molecular methods, including direct nucleic acid amplification and sequencing followed by phylogenetic comparisons or by the molecular identification of genes that directly account for the pathogenesis of the infectious process.
A strong area of interest is the application of new microbial genome-based techniques such as microarray applications for identification of pathogenic traits and features. As such, we hope to enter a new age in microbial disease diagnosis where disease is identified not based solely upon correlation with the presence of a potential pathogen, but based upon the identification of specific factors of the pathogen and host that result in the diseased state.
Publications
Choi K-s, Scorpio DG, Dumler JS. Anaplasma phagocytophilum ligation to TLR2 but not TLR4 activates macrophages for NF-kB nuclear translocation. J Infect Dis 2004 189:1921-1925.
Scorpio DG, Caspersen K, Ogata H, Park JH, Dumler JS. Restricted changes in major surface protein-2 (msp2) transcription after prolonged in vitro passage of Anaplasma phagocytophilum. BMC Microbiology 2004; 4:1.
Choi K-s, Grab DJ, Dumler JS. Anaplasma phagocytophilum infection induces protracted neutrophil degranulation. Infect Immun 2004; 72:3680-3.
Park J, Kim KJ, Choi K-s, Grab DJ, Dumler JS. Anaplasma phagocytophilum AnkA binds to granulocyte DNA and nuclear proteins. Cell Microbiol 2004; 6:743-751.
Scorpio DG, Akkoyunlu M, Fikrig E, Dumler JS. CXCR2 blockade influences Anaplasma phagocytophilum propagation but not histopathology in the mouse HGA model. Clin Diagn Lab Immunol 2004; 11:963-968.
Stone JH, Dierberg K, Aram G, Dumler JS. Human monocytic ehrlichiosis. JAMA. 2004; 292:2263-2270.
Affiliation: Johns Hopkins University
Country: USA