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Heather Melichar

Melichar, Heather

Associate Professor

Affiliation

Université de Montréal

Research Axes

Immunology-oncology

Contact information

Phone: 514 252-3400, poste4827

heather.melichar@umontreal.ca

laboratoiremelichar

Team

  • Mengqi Dong
  • Marion Dubuissez
  • Marilaine Fournier
  • Terrie Laplante Beauchamp
  • Marie-Ève Lebel
  • Mathieu Neault
  • Aditi Sood

With a PhD in immunology, Heather Melichar heads the T Cell Development and Function Research Unit. She is an associate professor in the Faculty of Medicine at Université de Montréal and an adjunct professor in 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 and uses knowledge from these studies to improve the effectiveness of cellular therapies.

Research Unit

T Cell Development and Function

This research unit focuses on the cellular and molecular mechanisms that regulate the development and function of T cells and uses knowledge from these studies to improve the effectiveness of cellular therapies.

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.
  • 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, doi: 10.1111/imcb.12287. [Epub ahead of print]
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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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  • Sood, A.*, Dong, M.*, Melichar, H.J. (2016) Preparation and applications of organotypic thymic slice cultures. Journal of Visualized Experiments, 114, e54355. *premier co-auteurs
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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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  • Melichar, H.J.*, Ross, J.O.*, Taylor, K.T., Robey, E.A. (2015) Stable interactions and sustained T cell receptor signaling typify thymocyte-thymocyte interactions that support negative selection. The Journal of Immunology. 194,1057-61. *premier co-auteurs
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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. *premier co-auteurs
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  • Ross, J.O.*, Melichar, H.J.*, Au-Yeung, B.B., Herzmark, P., Weiss, A., Robey, E.A. (2014) Two distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and TCR signaling patterns. Proceedings of the National Academy of Sciences, 111, E2550-2558. *premier co-auteurs
  • 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. *premier co-auteurs
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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. *premier co-auteurs
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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

  • 2015 New Investigator Award  (CIHR)
  • 2014 Junior 1 Research Scholar  (FRQS)
  • 2013 Postdoctoral fellowship  (CIRM)
  • 2007 Postdoctoral fellowship  (CIRM)
  • 2002 Graduate fellowship  (NIH)