- Postdoctoral Training at Laboratory of Systems Biology, National Institutes of Health (US);
- Ph.D., Emory University (US);
- BSc (hons), University of Warwick (UK)
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.
Lab page for Dr Mandl's Team: jmandl.lab.mcgill.ca