Through my thesis work I seek to understand how the macrophage, a professional phagocyte and innate immune effector cell, responds to damaging insults to its endolysosomal membranes. Macrophages incur damage in this way when they internalize microbial pathogens or particulate irritants capable of perforating host membranes. Whether macrophages have dedicated mechanisms to limit such damage and avoid ensuing infectious and chronic inflammatory pathologies is not well understood. By developing and applying novel, quantitative methods for measuring damage to lysosomes within macrophages, our lab has discovered an inducible property of macrophages that seems to fulfill a membrane protective role. We find that after exposure to certain stimulating factors (eg. LPS, IFN-γ, TNF-α) macrophages are better able to resist membrane damage to their lysosomes compared to resting macrophages that have not received such stimulation (Davis J. Immunol 2012). This phenomenon - of enhanced protection from lysosomal damage within activated macrophages - we have termed “inducible renitence.” The goals of my thesis research are (1) to gain a molecular understanding of the mechanisms underlying renitence and (2) to identify immunological contexts in which renitence acts.
2016-2017: Rackham Predoctoral Fellowship Award
2014-2016: Molecular Mechanisms in Microbial Pathogenesis Training Program pre-doctoral trainee
Wong, A., Marthi, M., Yoshida, S., Gregorka, B., Swanson, M., Swanson, J. TLR stimulation induces macropinocytosis and reinforces lysosomal integrity in macrophages. Gordon Research Conference and Seminar on Phagocytes, Waterville Valley, NH, June 2017.
Wong, A., Marthi, M., Gregorka, B., Davis, M., Chung C., Lieberman A., Swanson, M., Swanson, J. Mechanisms of lysosomal damage protection in macrophages. Gordon Research Conference and Seminar on Lysosomes and Endocytosis, Proctor Academy, Andover, NH, June 2016.
Wong, A., Marthi, M., Gregorka, B., Chung C., Lieberman A., Swanson, M., Swanson, J. Mechanisms of lysosomal membrane damage resistance in macrophages. American Society for Cell Biology Annual Meeting, San Diego, CA, December 2015.
Wong, A., Marthi, M., Gregorka, B., Davis, M., Swanson, M., Swanson, J. Mechanisms of lysosomal membrane damage responses in macrophages. Gordon Research Conference and Seminar on Phagocytes, Waterville Valley, NH, June 2015.