David M. Engman, MD, PhD

Professor of Pathology and Microbiology-Immunology
Feinberg School of Medicine

Research Interests:
Research in the Engman laboratory focuses on the molecular biology of trypanosomes, with particular emphasis on organelle biogenesis and the pathogenesis of trypanosomal diseases.

Trypanosomes are single-celled eukaryotic parasites that cause diseases such as African sleeping sickness and Chagas disease. They have complex life cycles involving insect and mammalian hosts and display a number of unique features that make them powerful model organisms for the study of genetics and molecular biology. The trypanosome genomes are approximately 50,000,000 bp in size and are organized in dozens to hundreds of linear chromosomes. Nuclear gene expression in trypanosomes is unusual. With few exceptions, there are no promotors and gene transcription does not occur with discrete start and stop points. Rather, an entire chromosome is transcribed in both directions from a single chromosome-internal initiation point, and individual mRNAs are generated via polyadenylation and the addition of a 39-nt spliced leader sequence to the 5' end of each coding region. Mitochondrial gene expression is equally remarkable. A number of mitochondrial genes are unidentifiable by DNA sequence, although the corresponding mRNAs are normal and are translated into proteins participating in a number of important mitochondrial processes. The "nonsense" genes are transcribed into pre-mRNAs whose sequences are "corrected" via the process of RNA editing: small antisense RNAs serve as templates for the addition or deletion of uridine residues to the transcripts, which ultimately results in mRNAs having intact coding sequences.

Selected Publications:
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. (in press).

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. (in press).

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, 490-9.

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, 522-35.

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, 3641-50.

Buchanan, K. T., Ames, J. B., Asfaw, S. H., Wingard, J. N., Olson, C. L., Campana, P. T., Araujo, A. P. and Engman, D. M. (2005). A flagellum-specific calcium sensor. J Biol Chem 280, 40104-11.