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Department of Physiology McGill University Life Sciences Complex (Bellini Pavilion) Room 364 3649 Promenade Sir William Osler Montreal, Quebec H3G 0B1 Office: 514-398-3149 judith.mandl [at] mcgill.ca Graduate & Postdoctoral positions available |
Research Area: Immunology, Molecular & Cell Biology
Research Description:
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.
Education:
Postdoctoral Training at Laboratory of Systems Biology, National Institutes of Health (US);
Ph.D., Emory University (US);
BSc (hons), University of Warwick (UK)
Selected Publications:
Schneider C, Shen C, Gopal AA, Douglas T, Forestell B, Kauffman KD, Rogers D, Artusa P, Zhang Q, Jing H, Freeman AF, Barber DL, King IL, Saleh M, Wiseman PW, Su HC, and Mandl JN*. (2020) “Migration-induced cell shattering due to DOCK8-deficiency causes a type-2 biased helper T cell response.” Nature Immunology 21:1528-1539.
Wortel IMN, Kesmir C, de Boer RJ, Mandl JN, Textor J. (2020) “Is T cell negative selection a learning algorithm?” Cells 9(3):690.
Sood A, Level ME, Fournier M, Rogers D, Mandl JN, Melichar HJ. (2019) “Differential interferon-gamma production potential among naïve CD4+ T cells exists prior to antigen encounter.” Immunology and Cell Biology 97(10):931-940.
Yuki KE, Marei H, Fiskin E, Eva MM, Gopal AA, Schwartzentruber JA, Majewski J, Cellier M, Mandl JN, Vidal SM, Malo D, Dikic I. (2019) “CYRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodeling and protects against bacterial infection.” Nature Microbiology 4(9):1516-1531.
Tong AA, Forestell B, Murphy DV, Nair A, Allen F, Myers J, Klauschen F, Shen C, Gopal AA, Huang AY, Mandl JN*. (2019) “Regulatory T cells differ from conventional CD4+ T cells in their recirculatory behaviour and lymph node transit times.” Immunology and Cell Biology 97(9): 787-798.
Mandl JN, Schneider C, Schneider DS, Baker ML. (2018) “Going to bat(s) for studies of disease tolerance.” Frontiers in Immunology 9:2112.
Vrisekoop N, Artusa P, Monteiro JP, Mandl JN. (2017) “Weakly self-reactive T cell clones can homeostatically expand when present at low numbers.” European Journal of Immunology 47(1):68-73.
Mandl JN, Barreiro L, Epstein J, Daszak P, Ahmed R, Virgin H, and Feinberg MB (2015) “Reservoir host immune responses to emerging zoonotic viruses.” Cell, 160 (1-2):20-35.
Vrisekoop N, Monteiro JP, Mandl JN*, and Germain RN (2014) “Revisiting thymic positive selection and the mature T cell repertoire for antigen.” Immunity 41(2):181-190.
Mandl JN, Monteiro JP, Vrisekoop N, and Germain RN (2013) “T cell positive selection uses self-ligand binding strength to optimize repertoire recognition of foreign antigens.” Immunity 38(2):263-74.
Mandl JN, Liou R, Klauschen F, Vrisekoop N, Monteiro JP, Yates AJ, Huang AY, and Germain RN (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.