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David M. Engman, MD, PhDProfessor
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To visit the Engman Lab website click here.
Our laboratory is engaged in two different lines of investigation:
Molecular Parasitology. Trypanosomes are single-celled parasites that cause human illnesses such as sleeping sickness and Chagas' disease. These organisms have complex life cycles involving both insect and mammalian hosts. The American trypanosome, Trypanosoma cruzi, is transmitted by reduviid bugs and evades the host immune response by penetrating host cells and differentiating into a form that replicates within the host cell cytoplasm. Transitions between the insect vector and the mammalian host are accompanied by complex morphologic and biochemical changes affecting virtually every part of the parasite cell. We are interested in the biogenesis of the mitochondria and flagella in these unique eukaryotic organisms, since these organelles are essential for cell survival as well as targets for the development of antiparasitic drugs.
Molecular Cardiology. 20 million Latin Americans are infected with T. cruzi and approximately 30 percent suffer from Chagas' heart disease. We are testing the hypothesis that immune responses directed toward both parasite antigens and heart antigens (i.e., autoimmunity) contribute to pathogenesis and have developed a mouse model of infection that exhibits both features. Mice develop severe myocarditis several weeks after infection that possesses all of the key features of the human disease, including strong parasite-specific and heart-specific humoral and cellular immunity. The overall objectives of these studies are (I) to elucidate the mechanisms by which parasite infection leads to cardiac inflammation, (ii) to determine the mechanisms by which autoreactive T cells are induced to proliferate and cause heart disease and (iii) to develop novel, immunomodulatory therapies for the treatment of myocarditis.
Tyler, K.M., Luxton, G.W.G., Applewhite, D.A., Murphy, S.C. and Engman, D.M. (2005) Responsive microtubule dynamics promote cell invasion by Trypanosoma cruzi. Cell. Microbiol. 7, 1579-1591. PMID: 16207245.
Buchanan, K.T., Ames, J.B., Asfaw, S.H., Wingard, J.N., Olson, C.L., Campana, P.T., Araújo, A.P.U. and Engman, D.M. (2005) A flagellum-specific calcium sensor. J. Biol. Chem. 280, 40104-40111. PMID: 16148003.
Hyland, K.V., Leon, J.S, Daniels, M.D., Giafis, N., Woods, L.M., Bahk, T.J., Wang, K. and Engman, D.M. (2007) Modulation of autoimmunity by treatment of an infectious disease. Infect. Immun. 75, 3641-3650. PMID: 17485457.
Fridberg, A., Olson, C.L., Nakayasu, E.S., Tyler, K.M., Almeida, I.C. and Engman, D.M. (2008) Sphingolipid synthesis is necessary for kinetoplast segregation and cytokinesis in Trypanosoma brucei. J. Cell Sci. 121, 522-535. PMID: 18230649.
Daniels, M.D., Hyland, K.V., Wang, K. and Engman, D.M. (2008) Recombinant cardiac myosin fragment induces experimental autoimmune myocarditis via activation of Th1 and Th17 immunity. Autoimmunity 41, 490-499. PMID: 18781477.
Hyland, K.V., Asfaw, S.H., Olson, C.L., Daniels, M.D. and Engman, D.M. (2008) Bioluminescent imaging of Trypanosoma cruzi infection. Int. J. Parasitol. 38, 1391-1400. PMID: 18511053.
Tyler, K.M., Fridberg, A., Toriello, K.M., Olson, C.L., Cieslak, J.A., Hazlett, T.L. and Engman, D.M. (2009) Flagellar membrane localization via association with lipid rafts. J. Cell Sci. 122, 859-866. PMID: 19240119.
Emmer, B.T., Souther, C., Toriello, K.M., Olson, C.L., Epting, C.L. and Engman, D.M. (2009) Identification of a palmitoyl acyltransferase required for protein sorting to the flagellar membrane. J. Cell Sci. 122, 867-874. PMID: 19240115.
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View Publications by David Engman listed in the National Library of Medicine (PubMed). |
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