Cancer Center Member
David M Engman, MD, PhD
Professor, Microbiology-Immunology; Feinberg School of Medicine
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Cancer Focused Research:
parasitology, heart, autoimmunity, microbiology, pathogenesis, disease, tropical, pathology, cytoskeleton
Molecular Cell Biology of Tropical Parasitic Diseases. 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. Pathogenesis and Treatment of Inflammatory Heart Disease. 20 million Latin Americans are infected with the American trypanosome Trypanosoma 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.