Department of Internal Medicine
Infectious Diseases Faculty
Medical School:
University of Rochester
Residency:
University of Michigan
Fellowship:
University of Virginia
Mary E. Wilson, M.D.
Kate Daum Professor of Internal Medicine and Microbiology
Molecular mechanisms of host-parasite interactions in leishmaniasis
Dr. Wilson's research focuses on the molecular and immunobiology of infection with the protozoan parasite, Leishmania chagasi, a cause of the disease visceral leishmaniasis. The lab examines interactions between the parasite and mammalian host that result in either survival or eradication of the parasite. Leishmania are obligate intracellular parasites of macrophages. The abundant parasite surface glycoprotein MSP is important for initial parasite attachment to macrophage receptors, evasion of complement killing, and intracellular survival. GP63 abundance parallels the virulence of the parasite. The lab studies molecular mechanisms regulating MSP expression in the parasite life stages. Leishmania are phagocytosed through caveolae on the macrophage surface, generating large membrane ruffles in the macrophage. Using confocal and electron microscopy the lab is investigating the routes through which the parasite moves into the infected cell, and how these relate to intracellular survival. Phagocytosis causes dramatic changes in macrophage gene expression, which is characterized with methods such as DNA microarray and Rnase protection assay. Macrophages down-modulate expression of several genes involved in microbicidal responses, and up-regulate expression of genes inhibiting inflammation, upon leishmania phagocytosis. The roles of several inhibitory factors (e.g. transforming growth factor-β, IL-10) in innate and adaptive immune responses to the parasite are under investigation.
Humans living in endemic areas develop widely divergent outcomes of L. chagasi infection, ranging from spontaneous cure to progressive, fatal visceral leishmaniasis. In collaboration with a professor in northeast Brazil, Dr. Wilson’s group is examining the hypothesis that polymorphic alleles at immune response genes contribute to an individual’s susceptibility to develop different outcomes after infection. Other studies are addressing recombinant parasite T cell antigens that could be used in antileishmanial vaccine development. The above studies make available to trainees basic molecular biology, protein biochemistry, immunology, and genetics techniques.
Honors, Awards, and Organizations
- Kate Daum Professorship
- American Association of Immunologists
- Diplomate, American Board of Internal Medicine and Board of Infectious Diseases
- American Society for Microbiology
- American Society of Cell Biology
- American Society for Tropical Medicine and Hygiene
- Infectious Diseases Society of America
- NIH Physician Scientist Award
- NIH FIRST Award
- Phi Beta Kappa
Select Publications
- Selma M. B. Jeronimo, Ashlee K. B. Holst, Sarra E. Jamieson, Richard Francis, Daniella R. A. Martins, Nicholas Ettinger, Eliana T. Nascimento, E. Nancy Miller, Heather J. Cordell, Priya Duggal, Terri H. Beaty, Jenefer M. Blackwell, and Mary E. Wilson. Genes at Human Chromosome 5q31.1 Regulate Delayed Type Hypersensitivity Responses Associated with Leishmania chagasi Infection. Genes and Immunity: 8:539-551, 2007.
- Gaur, U., S. C. Roberts, R. P. Dalvi, I. Corraliza, B. Ullman and M. E. Wilson. An Effect of Parasite-Encoded Arginase on the Outcome of Murine Cutaneous Leishmaniasis. J. Immunology: 179:8446-8453, 2007.
- Hsiao, C.-H. C., C. Yao, P. A. Storlie, J. E. Donelson, and M. E. Wilson. The major surface protease (MSP or GP63) in the intracellular amastigote life stage of Leishmania chagasi. Mol. Biochem. Parasitol.: 157(2): 148-159, 2008.
- Ettinger, N. A. and M. E. Wilson. Macrophage and T-cell gene expression in a model of early infection with the protozoan, Leishmania chagasi. PLoS Negl Trop Dis 2(6): e252. doi:10.1371/journal.pntd.0000252 (http://www.plosntds.org/doi/pntd.0000252) and Featured Cover Illustration.
Links of Interest