Jeffrey N. Weiser, M.D.

faculty photo
Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

Contact information
402A Johnson Pavilion
Department of Microbiology
University of Pennsylvania
Philadelphia, PA 19104-6076
Office: 215-573-3511
Fax: 215-573-4856
Education:
B.S. (Biological Sciences)
Stanford University, 1979.
M.D.
Harvard University, 1984.
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Description of Research Expertise

Research Interests
Molecular basis of infectious diseases.

Key words:
Bacterial pathogenesis, Streptococcus pneumoniae, Haemophilus influenzae, colonization, microbial competition.

Description of Research

The Weiser lab investigates the molecular basis of host-pathogen interaction for bacteria that reside in and infect the human respiratory tract. Most studies focus on the pathogenesis of Streptococcus pneumoniae because of its prominence as a cause of acute respiratory tract infection. Other pathogens under investigation in the laboratory include Haemophilus influenzae, Klebsiella pneumoniae and Staphylococcus aureus. Many projects focus on colonization of the mucosal surface of the upper airway, the initial step in the disease process. Both host and bacterial factors affecting colonization are under investigation. In general these studies utilize bacterial genetics to examine effects of specific microbial genes together with mouse models of colonization that allow for the use of genetically-modified hosts.

On-going projects examine:

How colonizing microbes stimulate and evade innate immune clearance mechanisms.
How the cellular immune responses acts to clear pneumococcal colonization.
Mechanisms that facilitate interspecies competition within a host.
Mechanisms of competition between co-colonizing pneumococci.
Pneumococcal interactions with neutrophils and mechanisms to evade killing by professional phagocytes.
The host-microbe battle for acquisition of iron on the mucosal surface and its implications for inflammation.
The potential of live attenuated vaccines that colonize and induce protective immunity but are avirulent
The role of phosphorycholine, a surface constituent of many respiratory tract pathogens, in pathogenesis.



Rotation Projects for 2006-2007

There are many possible projects in areas of bacterial genetics, host-pathogen interaction, and host immune response. Please contact Dr. Weiser directly.

Lab personnel:
Alistair Standish, Ph.D. – Postdoctoral Fellow
Michael Bachman MD, Ph.D. - Postdoctoral Fellow
Ankur Dalia - Grad Student
Kim Davis – Grad Student
Shigeki Nakamura MD, Ph.D. – Visiting Scholar
Thomas Clarke, Ph.D. - Postdoctoral Fellow
Sarah Clark – Grad Student
Elena Lysenko Ph.D. – Research Assistant
Aoife Roche – Research Assistant
Misha Shchepetov – Research Assistant
Rebecca Lijek – Grad Student
Genia Guseynova/Admin. Assistant

Selected Publications

Ratner Adam J, Lysenko Elena S, Paul Marina N, Weiser Jeffrey N: Synergistic proinflammatory responses induced by polymicrobial colonization of epithelial surfaces. Proceedings of the National Academy of Sciences of the United States of America 102(9): 3429-34, Mar 2005.

Weiser JN: Phase Variation in Streptococcus pneumoniae. Gram-positive Pathogens. In Vincent Fischetti (eds.). American Society for Microbiology Press, Washington, D.C. 2006.

Bender Matthew H, Weiser Jeffrey N: The atypical amino-terminal LPNTG-containing domain of the pneumococcal human IgA1-specific protease is required for proper enzyme localization and function. Molecular microbiology 61(2): 526-43, Jul 2006.

Lysenko Elena S, Clarke Thomas B, Shchepetov Mikhail, Ratner Adam J, Roper David I, Dowson Christopher G, Weiser Jeffrey N: Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing. PLoS pathogens 3(8): e118, Aug 2007.

Beisswenger Christoph, Coyne Carolyn B, Shchepetov Mikhail, Weiser Jeffrey N: Role of p38 MAP kinase and transforming growth factor-beta signaling in transepithelial migration of invasive bacterial pathogens. The Journal of biological chemistry 282(39): 28700-8, Sep 2007.

Davis Kimberly M, Akinbi Henry T, Standish Alistair J, Weiser Jeffrey N: Resistance to mucosal lysozyme compensates for the fitness deficit of peptidoglycan modifications by Streptococcus pneumoniae. PLoS pathogens 4(12): e1000241, Dec 2008.

Matthias Kathryn A, Roche Aoife M, Standish Alistair J, Shchepetov Mikhail, Weiser Jeffrey N: Neutrophil-toxin interactions promote antigen delivery and mucosal clearance of Streptococcus pneumoniae. Journal of immunology (Baltimore, Md. : 1950) 180(9): 6246-54, May 2008.

Kadioglu Aras, Weiser Jeffrey N, Paton James C, Andrew Peter W: The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nature reviews. Microbiology 6(4): 288-301, Apr 2008.

Zola Tracey A, Lysenko Elena S, Weiser Jeffrey N: Mucosal clearance of capsule-expressing bacteria requires both TLR and nucleotide-binding oligomerization domain 1 signaling. Journal of immunology (Baltimore, Md. : 1950) 181(11): 7909-16, Dec 2008.

Zhang Zhe, Clarke Thomas B, Weiser Jeffrey N: Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. The Journal of clinical investigation 119(7): 1899-909, Jul 2009.

Standish Alistair J, Weiser Jeffrey N: Human neutrophils kill Streptococcus pneumoniae via serine proteases. Journal of immunology (Baltimore, Md. : 1950) 183(4): 2602-9, Aug 2009.

Zola Tracey A, Lysenko Elena S, Weiser Jeffrey N: Natural antibody to conserved targets of Haemophilus influenzae limits colonization of the murine nasopharynx. Infection and immunity 77(8): 3458-65, Aug 2009.

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Last updated: 09/10/2009
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