Mitchell S. Dushay, Ph.D.
Research & Accomplishments
Most of the world's animal species lack antibodies and T cells (adaptive immunity), yet they still possess potent immune defenses to survive infections and reproduce. The fruit fly, Drosophila melanogaster, is a powerful model for the study of insect immunity. Drosophila research also has provided insight into innate immunity in mammals including humans. One of the projects in my laboratory is coagulation, which serves immune as well as physiological roles, but is still poorly understood in insects. In collaboration with Dr U. Theopold, Stockholm University, we have identified proteins in the larval clot, and the next steps are to learn how these proteins interact to form a clot, how coagulation is triggered and regulated, how clots contribute to wound closure and repair, and how they protect against infection.
Another project concerns lamins; intermediate filament proteins that form a matrix underlying the nuclear membrane. Lamins contribute to nuclear strength and shape, participate in cell division, and affect cell type-specific gene expression. Mutations in a human lamin gene cause a wide range of diseases, including muscular dystrophies and accelerated aging disorders such as Hutchinson-Guilford Progeria Syndrome – the rare disease that causes death by age 14 of atherosclerosis, heart attack, and stroke. Mutations in the Drosophila lamin (lam) gene cause early death. The few lam adults that emerge survive only a few days and are weak, uncoordinated, and flightless – they behave like old flies. Mutant larvae also move poorly and show immune defects. We are using molecular, bioinformatic, and functional genomic approaches to study what other genes are involved and how lam mutations cause these phenotypes. In addition to immunity, these experiments have implications for muscular dystrophy and aging.
Theopold, U., R. Krautz and M. S. Dushay (2014). "The Drosophila clotting system and its messages for mammals." Developmental & Comparative Immunology 42(1): 42 - 46.
Bajzek, C. and M. S. Dushay (2012). "A new in vivo capillary assay of coagulation in invertebrates." Invertebrate Survival Journal 9(2): 178 - 183.
Bajzek, C., A. M. Rice, S. Andreazza and M. S. Dushay (2012). "Coagulation and survival in Drosophila melanogaster fondue mutants." Journal of Insect Physiology 58(10): 1376 - 1381.
Chang, H. J., I. Dhanasingh, X. Gou, A. M. Rice and M. S. Dushay (2012). "Loss of Hemolectin reduces the survival of Drosophila larvae after wounding." Developmental and Comparative Immunology 36(2): 274 - 278.
Harbers, M., M. S. Dushay and P. Carninci (2012). "DeepCAGE: Genome-Wide Mapping of Transcription Start Sites." Book - Tag-based Next Generation Sequencing Edited by Matthias Harbers and Günter Kahl(WILEY-VCH Verlag GmbH & Co.KGaA, Weinheim, Germany): 23 - 46.
Markovic, P. M., P. Kylsten and M. S. Dushay (2009). "Drosophila lamin mutations cause melanotic mass formation and lamellocyte differentiation." Molecular Immunology 46(16): 3245 - 3250.
Bidla, G., T. Hauling, M. S. Dushay and U. Theopold (2009). "Activation of insect phenoloxidase after injury: endogenous versus foreign elicitors." Journal of Innate Immunology 1: 301 - 308.
Dushay, M. S. (2009). "Insect hemolymph clotting." Cellular and Molecular Life Sciences 66(16): 2643-2650.
Dushay, M. S. (2009). "Insect Hemolymph Clotting." Cell and Molecular Life Sciences 66: 2643-2650.
Lindgren, M., R. Riazi, C. Lesch, C. Wilehlmsson, U. Theopold, and M. S. Dushay (2008). "Fondue and Transglutaminase in the Drosophila larval clot." Journal of Insect Physiology 54: 586 – 592.
Muñoz-Alarcón, A., M. Pavlovic, J. Wismar, B. Schmitt, M. Eriksson, P. Kylsten, and M. S. Dushay (2007). "Characterization of lamin mutation phenotypes in Drosophila and comparison to human laminopathies." PLoS ONE Doi 10.1371/journal.pone.0000532
Agianian, B., C. Lesch, O. Loseva, and M.S. Dushay (2007). "Preliminary characterization of hemolymph coagulation in Anopheles gambiae larvae." Developmental and Comparative Immunology 31: 879 - 888.
Karlsson, C., A. M. Korayem, C. Scherfer, O. Loseva, M. S. Dushay, and U. Theopold (2004). "Proteomic analysis of the Drosophila larval hemolymph clot." J. Biological Chemistry 279: 52033 – 41.
Korayem, A. M., M. Fabbri, K. Takahashi, C. Scherfer, M. Lindgren, O. Schmidt, R.Ueda, M.S. Dushay, and U.Theopold (2004). "A Drosophila salivary gland mucin is also expressed in immune tissues: evidence for a function in hemolymph coagulation." Insect Biochemistry and Molecular Biology 34: 1297 - 1304.
Scherfer, C., C. Karlsson, O. Loseva, G. Bidla, A. Goto, J. Havemann, M. S. Dushay, and U. Theopold (2004). "Isolation and characterization of hemolymph clotting factors in Drosophila melanogaster by a pull-out method." Current Biology 14: 625 - 629.
Genetics Society of America
International Society of Developmental and Comparative Immunology
American Association for the Advancement of Science
American Journal of Molecular Biology