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    W. Nicholas Haining, BM, BCh

    Adjunct, Department of Immunology and Virology
    Assistant Professor, Pediatric Oncology
    Assistant Professor of Pediatrics, Harvard Medical School
    Associate Member, Broad Institute of MIT and Harvard
     
     

    About Haining Lab

    The Haining Laboratory studies the molecular mechanisms that impair T cell function in cancer and chronic infections using cellular immunology, chemical biology, and functional genomics to understand the regulatory circuits that drive loss of function by exhausted T cells. We are interested in developing novel therapeutic approaches to rescue function in exhausted T cells.

    In our studies of functional and dysfunctional exhausted CD8 T cells, we used transcriptional profiling of rare populations of virus-specific CD8 T cells from human blood to identify the molecular differences between effective and ineffective T-cell responses in HIV. These studies revealed a mechanism by which PD-1 coordinately upregulates a program of genes, including the transcription factor BATF, which impairs T-cell function. Using chemical screens to identify small molecules that reverse inhibition caused by the receptor PD-1, we are developing novel genetic and computational approaches to match active compounds to their target molecules.

    We have also developed a novel strategy for in vivo testing of regulators of T cell function in which an inducible shRNA construct is transduced into hematopoietic stem cells using a lentiviral vector, enabling in vivo gene knockdown without subsequent manipulation. This approach is particularly valuable for studying key genes that control endogenous tumor immunity.