Research in the Engman-Epting Laboratories

 

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. The African trypanosome, Trypanosoma brucei, is transmitted by tsetse flies and evades host immunity via antigenic variation. Transitions between the insect and mammalian hosts are accompanied by complex morphologic and biochemical changes affecting virtually every part of the parasite cell. We are interested in cell biology of trypanosomes with special attention to (1) the flagellum, a ciliary structure important for motility and cell signaling, (2) molecular mechanisms of host cell invasion and endothelial transmigration, (3) drug discovery, (4) molecular basis of tissue tropism of trypanosomes and (4) vaccine development.

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 (1) to elucidate the mechanisms by which parasite infection leads to cardiac inflammation, (2) to determine the mechanisms by which autoreactive T cells are induced to proliferate and cause heart disease and (3) to develop novel, immunomodulatory therapies for the treatment of myocarditis.