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职称:Professor.
所属学校:University of Maryland-College Park
所属院系:College of Computer, Mathematical and Natural Sciences
所属专业:Biological and Physical Sciences
联系方式: 301-405-9601
We are interested in molecular strategies utilized by intracellular pathogens to interact with their host cells, and on fundamental cell biological processes subverted by pathogens during infection. Our studies of the mechanism by which the protozoan Trypanosoma cruzi invades host cells uncovered a previously unrecognized, ubiquitous process of Ca2+ dependent mobilization and fusion of lysosomes with the plasma membrane. This Ca2+-regulated lysosome exocytosis pathway is subverted by the parasites as a strategy to form a membrane-bounded vacuole, through which they gain access to host cells. We also discovered that Ca2+-triggered lysosomal exocytosis plays a central role in the mechanism by which mammalian cells reseal after wounding. We are currently actively investigating the role of the lysosomal enzyme acid sphingomyelinase in triggering an endocytic process responsible for removing toxin pores and other lesions from the plasma membrane. In addition, we have several projects analyzing the molecular mechanisms of intracellular survival of the trypanosomatid Leishmania, a parasite that causes serious human disease worldwide.
Ben-Othman, R., Flannery, A.R., Miguel, D.C., Ward, D.M., Kaplan, J. and Andrews, N.W. Leishmania-mediated inhibition of iron export promotes parasite replication in macrophages. PloS Pathogens, 10:e1003901. 2014. Corrotte, M., Almeida P.E., Tam, C., Castro-Gomes, T., Fernandes, M.C., Millis, B.A., Cortez, M., Miller, H., Song, W., Maugel, T.K. and Andrews, N.W. Caveolae internalization repairs wounded cells and muscle fibers. eLife 2013:2:e00926, 2013. Flannery, A.R., Renberg, R.L. and Andrews, N.W. Pathways of iron acquisition and utilization in Leishmania. Curr. Op. Microbiol. doi:pii: S1369-5274(13)00119-7. 10.1016/j.mib.2013.07.018, 2013. Mittra, B., Cortez, M., Haydock, A., Ramasamy, G., Myler, P.J. and Andrews, N.W. Iron uptake controls the generation of Leishmania infective forms through regulation of ROS levels. J. Exp. Med. 210: 401-416, 2013. Corrotte, M., Fernandes, M.C., Tam, C. and Andrews, N.W. Toxin pores endocytosed during plasma membrane repair traffic into the lumen of MVBs for degradation. Traffic 13:483-494, 2012. Huynh, C., Yuan, X., Miguel, M.C., Renberg, R.L., Potchenko, O., Philpott, C.C., Hamza, I. and Andrews, N.W. Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1. PLoS Pathogens, 8:e1002795. Epub 2012.