Associate Professor
Affiliation
Université de Montréal
Research Axes
Team
- Marie-Ève Lebel, PhD
- Marilaine Fournier, PhD
- Sébastien This, PhD
- Stefanie Valbon Fernandes Garcia
- Ève Mallet Gauthier
Heather Melichar earned a PhD in immunology and heads the T cell Development and Function Research Unit. She is an associate professor in the the Department of Medicine at the Université de Montréal with an affiliation with the Department of Microbiology, Infectious Diseases and Immunology. Her laboratory is interested in the cellular and molecular mechanisms that regulate the development and function of T cells; her group uses knowledge from these studies to improve the effectiveness of cellular therapies.
Research Unit
T Cell Development and Function
Research interests
The unit’s goal is to understand the fundamental processes of T cell development and function. The team approaches this problem from a cellular perspective by studying how T cells communicate with support cells in the thymic microenvironment as they develop and with target cells during the immune response. To achieve these research goals, the team uses a variety of techniques to maintain, manipulate and probe the three-dimensional space of the thymus. These techniques include multiparametric flow cytometry, two-photon microscopy of live tissue, mouse and human organotypic culture, and genetically engineered mouse models. The unit's current goals are to:
- Examine how the T cell receptor signal threshold between positive and negative selection of thymocytes changes throughout ontogeny. How do these differences in thymic selection in neonates and adults impact T cell effector function in the peripheral lymphoid organs?
- Study how self-antigen, when presented by different medullary thymic epithelial cell (mTEC) subsets, affects negative selection. In particular, we are examining how this impacts thymocyte:mTEC interactions and their development.
- Investigate the role of a novel protein:protein interaction between T cells and tumour cells in suppressing tumour-specific T cell function. We are further characterizing this interaction, mechanism of action, and potential as a therapeutic target to treat cancer.
Publications
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Sood, A., Lebel, MÈ., Dong, M., Fournier, M., Vobecky, S.J., Haddad, É., Delisle, JS., Mandl, J.N., Vrisekoop, N.#, Melichar, H.J.# (2021). CD5 levels define functionally heterogeneous populations of naive human CD4+ T cells. European Journal of Immunolology. 51:1365-1376. #co-coressponding authors.
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Dong, M., Audiger, C., Adegoke, A., Lebel, MÈ., Valbon, S.F., Anderson, C.C., Melichar, H.J.#, Lesage, S.# (2021). CD5 levels reveal distinct basal T-cell receptor signals in T cells from non-obese diabetic mice. Immunology & Cell Biology, 99:656-667. #co-corresponding authors.
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Lebel, MÈ., Coutelier, M., Galipeau, M., Kleinman, C.L., Moon, J.J., Melichar, H.J. (2020). Differential expression of tissue-restricted antigens among mTEC is associated with distinct autoreactive T cell fates. Nature Communications, 11:3734.
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Sood, A., Lebel, MÈ., Fournier, M., Rogers, D., Mandl, J.N., Melichar, H.J. (2019). Differential interferon-gamma production potential among naïve CD4+ T cells exists prior to antigen encounter. Immunology & Cell Biology, 97:931-940.
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Dong, M., Artusa, P., Kelly, S.A., Fournier, M., Baldwin, T.A., Mandl, J.N., Melichar, H.J. (2017). Alternations in the thymic selection threshold skew the self-reactivity of the T cell receptor repertoire in neonates. The Journal of Immunology, 199, 965-973.
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Halkias, J., Yen, B., Reinhartz, O., Taylor, K.T., Winoto, A., Robey, E.A., Melichar, H.J. (2015). Conserved and divergent aspects of human T cell development and migration in humanized mice. Immunology & Cell Biology, 93, 716-726.
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Au-Yeung, B.B.*, Melichar, H.J.*, Ross, J.O., Cheng, D.A., Zhang, C., Shokat, K.M., Robey, E.A., Weiss, A. (2014). Quantitative and Temporal Requirements Revealed for Zap-70 catalytic activity during T cell development. Nature Immunology, 15, 687-694. *equal contribution.
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Melichar, H.J.*, Ross, J.O.*, Herzmark, P., Hogquist, K.A., Robey, E.A. (2013). Distinct temporal patterns of T cell receptor signaling during positive versus negative selection in situ. Science Signaling, 6, ra92. *equal contribution.
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Halkias, J.*, Melichar, H.J.*, Taylor, K.T., Ross, J.O., Yen, B., Cooper, S.B., Winoto, A., Robey, E.A. (2013). Opposing chemokine gradients control human thymocyte migration in situ. Journal of Clinical Investigation, 123, 2131-2142. *equal contribution.
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Melichar, H.J., Narayan, K., Der, S., Hiraoka, Y., Gardiol, N., Jeannet, G., Held, W., Chambers, C., Kang, J. (2007). Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13. Science, 315, 230-233.
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Education
Postdoctoral fellowship
University of California, Berkeley
PhD in immunology
University of Massachusetts Medical School
BSc in biology
Boston College
Awards
- 2022 Senior Research Scholar (FRQS)
- 2020 Junior 2 Research Scholar (FRQS)
- 2015 New Investigator Award (CIHR)
- 2014 Junior 1 Research Scholar (FRQS)