Shalini Low-Nam

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

Our group is focused on discovering molecular mechanisms of cellular decision-making. We have introduced a molecular impulse-response function to map the complete history of input accumulation (with single molecule precision), through signal integration, and up to the outcome, in the form of a cellular behavioral response. We focus on understanding how single cells satisfy activation thresholds, in order to develop strategies to modulate these responses. We work on both tumor (breast and pancreatic) and immune cells (T cells and macrophages) in the complex cancer microenvironment. Many key impulses are detected at interfaces between these cells; thus, we make quantitative measurements of the dynamic landscape (biophysical features) of intercellular spaces that modulate signal propagation. We use high resolution microscopy to directly observe the impulse-response function and combine in vitro reconstitution and live cell approaches to understand key activation mechanisms (growth, polarization, cytokine secretion, migration, etc) during cancer progression.

Selected Publications:

Lin, J.J.*, Low-Nam, S.T.*, Alfieri, K.A., Groves, J.T. (2019) Mapping the stochastic sequence of individual ligand-receptor binding events to the cellular decision to activate: T cells act on the rare events. Science Signaling. 12(564). *These authors contributed equally.

Hoppe, A.D. Scott, B.S., Sochacki, K.A., Low-Nam, S.T., Bailey, E., Luu, Q.A., Hor, A., Dickey, A.M. Smith, A., Kerkvliet, J.G., Taraska, J.W. (2018). Membrane bending occurs at all stages of clathrin-coat assembly and defines endocytic dynamics. Nature Communications. 9(1):419.

Pielak, R.M., O’Donoghue, G.P., Lin, J.J., Alfieri, K.N., Fay, N.C., Low-Nam, S.T., Groves, J.T. (2017). Early T cell receptor signals globally modulate ligand:receptor affinities during antigen discrimination. PNAS. 114(46):12190-12195.

Lee, Y.K., Low-Nam, S.T., Chung, J.K., Hansen, S.D., Lam, H.Y.M., Alvarez, S., Groves, J.T. (2017). Mechanism of SOS PR-domain autoinhibition revealed by single molecule assays on native protein from lysate. Nature Communications. 8: 1-11.

Lou, J., Low-Nam, S.T., Kerkvliet, J.G., Hoppe, A.D. (2014). Delivery of the CSF-1R to the lumen of macropinosomes promotes its destruction in macrophages. J. Cell Sci. 127: 5228-5239.

Hoppe, A.D. and S.T. Low-Nam (2014). Live-Cell TIRF Imaging of Molecular Assembly and Plasma Membrane Topography. Cell Membrane Nanodomains: from Biochemistry to Nanoscopy. 261-280.

Low-Nam, S.T., Lidke, K.A., Cutler, P.J., Roovers, R.C., van Bergen en Henegouwen, M.P., Wilson, B.S., Lidke, D.S. (2011). ErbB1 dimerization is promoted by domain co-confinement and stabilized by ligand. Nature Struct. and Mol. Biol. 18: 1244-1249. Profiled in Bessman, N.J., Lemmon, M.A. (2012). Finding the missing links in EGFR. Nature Struct. and Mol. Biol. 19: 1-3.

Lidke, D.S., Low-Nam, S.T., Cutler, P.J., Lidke, K.A. (2011). Determining FcεRI diffusional dynamics via single quantum dot tracking. Methods in Mol. Biol. 748: 121-132