Dennis M. Dwyer, Ph.D.
Chief, Cell Biology Section
Senior Investigator
Description of Research Program
The cell and molecular biology of the protozoan pathogen, leishmania, is investigated as a model of human parasitism. The goals of this research are to identify and characterize the basic mechanisms which facilitate this parasite's survival in its insect vector and human hosts. To that end, the basic biochemical functions and the structure of the genes encoding surface membrane and secreted proteins (enzymes) are investigated to define their roles in parasite survival and development.
Several unique parasite enzymes are currently being studied: a family of constitutively expressed acid phosphatases, a surface membrane 3´-nucleotidase/nuclease, and a developmentally expressed chitinase. Homologous gene-deletion (knockout), over-expression, and anti-sense methods are being used to determine/verify whether these proteins are critical to the survival of these organisms. In addition, plasmid constructs containing epitope tags (e.g., HA, Green Fluorescent Protein-tags, etc.) are being used to study the cellular trafficking and targeting of these unique parasite proteins. Such essential proteins could provide new targets for diagnostics and innovative chemo- and immunotherapeutic intervention for this important group of human pathogens.
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Immunofluorescence of L. donovani promastigotes. The microtubule cytoskeleton is visualized with anti-α-tubulin antibody (red), LdK39 kinesin is visualized with anti-rK39 antibody (green), nuclease and kinetoplast DNA are visualized with DAPI (blue). LdK39 kinesin accumulates at anterior and posterior cell poles and follows a pattern consistent with cortical cytoskeleton.
(Source: Noel Gerald, 2007) |
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"The Cell Mates"
From left to right: Dennis Dwyer, Noel Gerald, Glen McGugan, Courtney Kiphart, Josh Owings, Manju Joshi |
Awards
Henry Baldwin Ward Medalist (American Society of Parasitologists); Honorary Fellow of the Liverpool School of Tropical Medicine, Liverpool University, UK; Alumni Citation Award (Montclair State University); The NIH Director's Award; Phi Kappa Phi; Sigma Xi; Who's Who in Science and Engineering; Who's Who in Medicine and Health Care; NATO Collaborative Research Grants; U.S.-Israel Binational Science Foundation Research Grants
Memberships
- American Association for the Advancement of Science
- American Society for Biochemistry and Molecular Biology
- American Society for Cell Biology
- American Society for Microbiology
- American Society of Parasitologists
- American Society of Tropical Medicine and Hygiene
- Society of Protozoologists
Editorial Boards
- Experimental Parasitology, Journal of Eukaryotic Microbiology, Tropical Medicine Abstracts
- Ad hoc reviewer for several other parasitology journals and various biochemistry, cell biology, and infectious disease journals
Grant Review Boards
AIBS Parasitic Diseases Review Panel; Medical Review Panel (United States Agency for International Development); External Grant Reviewer for several tropical disease research committees (U.N.D.P./World Bank/WHO); Cell Biology Section (United States National Science Foundation); United States-Israel Binational Science Foundation; NATO Scientific Affairs Division; The Wellcome Trust; Medical Research Council of Canada; British Columbia Health Research Foundation, Canada; National Research Council (National Academy of Sciences, U.S.A.)
Selected Recent Publications
(View list in PubMed.)
Debrabant A, Joshi MB, Pimenta PF, Dwyer DM. Generation of Leishmania donovani axenic amastigotes: their growth and biological characteristics. Int J Parasitol. 2004. 34(2):205-17.
Joshi MB, Mallinson DJ, Dwyer DM. The human pathogen Leishmania donovani secretes a histidine acid phosphatase activity that is resistant to proteolytic degradation. J Eukaryot Microbiol. 2004. 51(1):108-12.
Porter-Kelley JM, Gerald NJ, Engel JC, Ghedin E, Dwyer DM. LdARF1 in trafficking and structural maintenance of the trans-Golgi cisternal network in the protozoan pathogen Leishmania donovani. Traffic. 2004. 5(11):868-83.
Joshi MB, Rogers ME, Shakarian AM, Yamage M, Al-Harthi SA, Bates PA, Dwyer DM. Molecular characterization, expression, and in vivo analysis of LmexCht1: the chitinase of the human pathogen, Leishmania mexicana. J Biol Chem. 2005. 280(5):3847-61.
Gerald NJ, Coppens I, Dwyer DM. Molecular dissection and expression of the LdK39 kinesin in the human pathogen, Leishmania donovani. Mol Microbiol. 2007. 63(4):962-79.
Joshi MB, Dwyer DM. Molecular and functional analyses of a novel class I secretory nuclease from the human pathogen, Leishmania donovani. J Biol Chem. 2007. 282(13):10079-95.
Special Interest Groups: Cell Biology, Protein Trafficking
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