|Department of Physiology|
Life Sciences Complex (Bellini Pavilion)
3649 Promenade Sir William Osler
Montreal, Quebec H3G 0B1
judith.mandl [at] mcgill.ca
Graduate & Postdoctoral positions available
Research Area: Immunology, Molecular & Cell Biology
T cells are essential to immune protection. They achieve both exquisite specificity and broad coverage for possible antigens by expressing αβT cell receptors (TCR) that are generated by a diversification process termed somatic recombination. The initiation of a T cell response has two important requirements: a T cell repertoire has to include a T cell with the right antigen specificity, and this specific T cell has to find the antigen in the body when it is present. My research group focuses on two critical aspects of T cell function: (1) their trafficking between the blood and secondary lymphoid organs, and their mobile behaviour within lymphoid organs, that enables them to survey the body for foreign antigen, and (2) the role of interactions with self-peptides presented by Major Histocompatibility Complex (MHC) molecules in establishing and maintaining an effective T cell receptor repertoire. Our goal is to gain insight into the mechanisms by which perturbations in T cell trafficking can lead to immunodeficiency, altered host-pathogen responses, or impaired T cell maintenance. We want to understand how pre-existing heterogeneity among naïve CD4 T cells impacts their function during acute and chronic infections, how T cell compete for cellular interactions that are important to their homeostasis, and how CD4 T cell effector differentiation is dysregulated by changes in their migratory behaviour. We use state-of-the art 2-photon intravital and multi-parameter confocal microscopy to quantitatively investigate the dynamic behaviour of individual T cells in real time within the complex tissues in which the processes regulating their activation and homeostasis are orchestrated. Our work will provide a framework for developing better therapies to treat immunological diseases or to harness the function of T cells in treating or preventing infections.
Postdoctoral Training at Laboratory of Systems Biology, National Institutes of Health (US);
Ph.D., Emory University (US);
BSc (hons), University of Warwick (UK)
Mandl, J.N., Feinberg, M.B. (2015) “Robust and sustained immune activation in human Ebola virus infection.” Proc Natl Acad Sci USA 112(15):4518-9
Mandl, J.N., Barreiro, L., Epstein, J., Daszak, P., Ahmed, R., Virgin, H., and Feinberg, M.B. (2015) “Reservoir host immune responses to emerging zoonotic viruses.” Cell 160 (1-2):20-35.
Zhang, Q., Dove, C., Strauss-Albee, D., Garcia, J., Mandl, J.N., Grodick, R., Chandler-Brown, D., Jing, H., Kim, E., Lenardo, T.E., Matthews, H.F., Freeman, A.F., Cornall, R.J., Germain, R.N., Mueller, S.N., and Su, H. (2014) “DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity.” Journal of Experimental Medicine 211(13):2549-66.
Textor, J., Hendrickson, S.E., Mandl, J.N., von Andrian, U.H., Westermann, J., de Boer, R.J., and Beltman, J.B. (2014) “Random Migration and Signal Integration Promote Rapid and Robust T cell Recruitment.” PLoS Computational Biology 10(8): e1003752.
Vrisekoop, N., Monteiro, J.P., Mandl, J.N., and Germain, R.N. (2014) “Revisiting thymic positive selection and the mature T cell repertoire for antigen.” Immunity 41(2):181-190.
Mandl, J.N., Torabi-Parizi, P., and Germain, R.N. (2014) “Visualization and dynamic analysis of host-pathogen interactions.” Curr. Opin. Immunol. 29:8-15.
Bouma, H.R., Mandl, J.N., Strijkstra, A.M., Boerema, A.S., Kok, J.W., van Dam, A., Ijzerman, A., Kroese, F.G., Henning, R.H. (2013) “5’AMP impacts lymphocyte recirculation through activation of A2B receptors.” J. Leukocyte Biology, 94(1):89-98.
Mandl, J.N., Monteiro, J.P., Vrisekoop, N., and Germain, R.N. (2013) “T cell positive selection uses self-ligand binding strength to optimize repertoire recognition of foreign antigens.” Immunity 38(2):263-74.
Mandl, J.N., Liou, R., Klauschen, F., Vrisekoop, N., Monteiro, J.P., Yates, A.J., Huang, A.Y., and Germain, R.N. (2012) “Quantification of lymph node transit times reveals differences in antigen surveillance strategies of naïve CD4 and CD8 T cells.” Proc Natl Acad Sci USA 109(44):18036-41.
Meteyer, C.U., Barber, D., Mandl, J.N. (2012) “Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome.” Virulence 3(7).
Lee, M., Mandl, J.N., Germain, R.N., and Yates, A.J. (2012) “The race for the prize – T cell trafficking strategies.” Blood 120(7):1432-8.