Heather Melichar

Office Phone: (514)252-3400 ext.: 4827
Fax: (514)253-7626
Lab Phone: (514)252-3400 ext.: 4658
heatherjmelichar@gmail.com

Research Axis  Immunology-Oncology
Research Unit  T cell development and function

TITLE

  • Assistant Professor

EDUCATION

  • 2007-2013 Post-doctoral fellow (Ellen Robey), University of California, Berkeley, USA
  • 2000 -2006 PhD., Immunology (Joonsoo Kang), University of Massachusetts Medical School, USA
  • 1995-1999 B.S. , Biology, Boston College, Massachusetts, USA  

DISTINCTIONS AND ACHIEVEMENTS

  • 2015-2020 CIHR New Investigator Award
  • 2014-2018 FRSQ Junior 1
  • 2013 CIRM Postdoctoral Fellowship
  • 2007-2009 CIRM Postdoctoral Fellowship
  • 2002-2003 NIH Immunology/Virology Predoctoral Training Grant

research interests

    The goal of our lab is to understand the fundamental processes of T cell development and function. We approach this problem from a cellular perspective, by studying how T cells communicate with support cells in the thymic microenvironment throughout their development and with target cells during an immune response. For this work, we make use of a variety of techniques that allow us to maintain, manipulate, and probe the intact 3D dimensional space of the thymus, including multiparametric flow cytometry, two-photon microscopy of live tissue, mouse and human organotypic culture, and genetically engineered mouse models. We are currently:

    1. Examining 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?
    2. Studying 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 developmental outcome.
    3. Investigating the role of a novel protein:protein interaction between T cells and tumor cells in suppressing tumor-specific T cell function. We are further characterizing the interaction, the mechanism of action, and potential as a therapeutic target to treat cancer.
       

    Selected papers

    • Halkias, J., Yen, B., Reinhartz, O., Taylor, K.T., Winoto, A., Robey, E.A., and Melichar, H.J.   (2015) Conserved and divergent aspects of human T cell development and migration in humanized mice. Immunology & Cell Biology. Epub.
    • Melichar, H.J.*, Ross, J.O.*, 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
    • Au-Yeung, B.B.*, Melichar, H.J.*, Ross, J.O., Cheng, D.A., Zhang, C., Shokat, K.M., Robey, E.A., and 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
    • 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., and Robey, E.A.  (2013) Low potency ligands and peptide presentation by thymic stromal cells induce brief, intermittent TCR signals during T cell positive selection in situ. Science Signaling, 6, ra92. *premier co-auteurs
    • Halkias, J.*, Melichar, H.J.*, Taylor, K.T., Ross, J.O., Yen, B., Cooper, S.B., Winoto, A., and Robey, E.A. (2013) Opposing chemokine gradients control human thymocyte migration in situ. Journal of Clinical Investigation, 123, 2131-2142. *premier co-auteurs
    • Dzhagalov, I.L., Melichar, H.J., Ross, J.O., Herzmark, P., and Robey, E.A. (2012)  Two-photon imaging of the immune system. Current Protocols in Cytometry, 60, 12.26.1-12.26.20.
    • Melichar, H.*, Li. O.*, Ross, J., Haber, H., Cado, D., Nolla, H., Robey, E.A., and Winoto, A. (2011) Comparative study of hematopoietic differentiation between human embryonic stem cell lines. PLoS One, 6, e19854. *premier co-auteurs
    • Melichar, H.J.*, Li, O.*, Herzmark, P.*, Padmanabhan, R.K., Oliaro, J., Ludford-Menting, M.J., Bousso, P., Russell, S.M., Roysam., B., and Robey, E.A. (2011) Quantifying subcellular distribution of fluorescent fusion proteins in cells migrating within tissues. Immunology & Cell Biology, 89, 549-557. *premier co-auteurs
    • Melichar, H.J., Narayan, K., Der, S., Hiraoka, Y., Gardiol, N., Jeannet, G., Held, W., Chambers, C., and Kang, J. (2007) Regulation of gd versus ab T lymphocyte differentiation by the transcription factor Sox13. Science, 315, 230-233. 

    Complete list of Dr H. Melichar's publications  

     

    ADDITIONAL INFORMATIONs

    Grants 

    • Hôpital Maisonneuve-Rosemont Foundation
    • Cole Foundation Transition Grant
    • FRQS Establishment of Young Investigators Grant
    • SickKids Foundation/CIHR-IHDCYH New Investigator Research Grant
    • CIHR Operating Grant
    • CCSRI Innovation Grant