Dumler, J. Stephen

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






Email

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

Research Grants

  1. Anaplasma regulation of host granulocyte functions
  2. John Stephen Dumler; Fiscal Year: 2007
  3. Anaplasma regulation of host granulocyte functions
  4. John Stephen Dumler; Fiscal Year: 2007
  5. Virulence and Immunity of Granulocytic Ehrlichiae
  6. John Stephen Dumler; Fiscal Year: 2007
  7. Anaplasma regulation of host granulocyte functions
  8. John Stephen Dumler; Fiscal Year: 2008

Publications

  1. Analysis of genetic identity of North American Anaplasma phagocytophilum strains by pulsed-field gel electrophoresis
  2. J S Dumler
  3. Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
  4. J Clin Microbiol 41:3392-4
  5. Human granulocytic anaplasmosis and macrophage activation
  6. J Stephen Dumler
  7. Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  8. Clin Infect Dis 45:199-204
  9. Human granulocytic anaplasmosis and Anaplasma phagocytophilum
  10. J Stephen Dumler
  11. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  12. Emerg Infect Dis 11:1828-34
  13. Anaplasma and Ehrlichia infection
  14. J Stephen Dumler
  15. Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  16. Ann N Y Acad Sci 1063:361-73
  17. Anaplasma phagocytophilum delay of neutrophil apoptosis through the p38 mitogen-activated protein kinase signal pathway
  18. Kyoung Seong Choi
  19. Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 624, Baltimore, MD 21205, USA
  20. Infect Immun 73:8209-18
  21. Detection of Anaplasma phagocytophilum DNA in Ixodes ticks (Acari: Ixodidae) from Madeira Island and Setubal District, mainland Portugal
  22. Ana Sofia Santos
  23. Instituto Nacional de Saúde Dr Ricardo Jorge, Aguas de Moura, Portugal
  24. Emerg Infect Dis 10:1643-8
  25. Molecular diagnosis of human granulocytic anaplasmosis
  26. J Stephen Dumler
  27. Department of Pathology, The Johns Hopkins Medical Institutions, Ross Research Building, Room 624, 720 Rutland Avenue, Baltimore, MD 21205 USA
  28. Expert Rev Mol Diagn 4:559-69
  29. Molecular methods for ehrlichiosis and Lyme disease
  30. J Stephen Dumler
  31. Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Ross Research Building, Room 624, 720 Rutland Avenue, Baltimore, MD 21205, USA
  32. Clin Lab Med 23:867-84, vi
  33. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment
  34. J Stephen Dumler
  35. Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  36. Clin Infect Dis 45:S45-51
  37. Demonstration of OspC type diversity in invasive human lyme disease isolates and identification of previously uncharacterized epitopes that define the specificity of the OspC murine antibody response
  38. Christopher G Earnhart
  39. Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0678, USA
  40. Infect Immun 73:7869-77


  43. http://www.labome.org/expert/usa/johns/dumler/j-stephen-dumler-356737.html