Norma W. Andrews

We are interested in molecular strategies utilized by intracellular pathogens to interact with their host cells, and on fundamental cell biological processes that are subverted by pathogens during infection. Our studies of the mechanism by which the protozoan Trypanosoma cruzi invades host cells have 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. Current projects include the study of signaling pathways involved in lysosome mobilization and trypanosome entry, molecular mechanisms of intracellular survival of the trypanosomatid Leishmania, and the role of a novel family of agonist-processing serine oligopeptidases we identified in trypanosomatids and bacterial pathogens. In addition, we are actively investigating the molecular mechanisms regulating Ca2+-triggered exocytosis of lysosomes in mammalian cells, and the role of this process in the repair of wounded membranes.

Idone, V., Tam, C., Goss, J., Toomre, D., Pypaert, M. and Andrews, N.W. Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis. J. Cell Biol. 180:905-914 , 2008.

Idone, V, Tam, C and Andrews, N.W. Two-way traffic in route to plasma membrane repair. Trends in Cell Biology 18:552-559, 2008.

Wilson, J., Huynh, C., Kennedy, K.A., Ward, D.M., Kaplan, J., Aderem, A. and Andrews, N.W. Control of parasitophorous vacuole expansion by LYST/Beige restricts Leishmania amazonensis intracellular growth. PLoS Pathogens 4:e1000179, 2008.

Huynh, C, Sacks, D.L. and Andrews, N.W. A Leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes. J. Exp. Med. 203: 2363-2375, 2006.

Czibener, C., Sherer, N.M., Mothes, W. and Andrews, N.W. Ca2+ and Synaptotagmin VII-dependent
delivery of lysosomal membrane to nascent phagosomes. J. Cell Biol. 174:997-1007, 2006.

Arantes, R.M.E. and Andrews, N.W. A role for synaptotagmin VII-regulated exocytosis in neurite outgrowth from primary sympathetic neurons. J. Neurosci. 26: 4630-4637, 2006.

Andrews, N. W. Membrane Repair and Immunological Danger. EMBO reports 6: 826-830, 2005.

Huynh, C. Roth, D., Ward, D.M., and Andrews, N.W. Defective lysosomal exocytosis and plasma membrane repair in Chediak-Higashi cells. Proc. Natl. Acad. Sci. 101: 16795-16800, 2004.

Roy, D., Liston, D.R., Idone, V.J., Di, A., Nelson, D.J., Pujol, C., Bliska, J.B., Chakrabarti, S and Andrews, N.W. A process for controlling intracellular bacterial infections induced by membrane injury. Science 304: 1515-1518, 2004.

Andrade, L.O. and Andrews, N.W. Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells. J. Exp. Med. 200: 1135-1143, 2004.

Burroughs Wellcome Molecular Parasitology Scholar Award and a MERIT award from the National Institutes of Health

Ph.D. University of Sao Paulo, Brazil, 1983