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Home > Molecular Oncology > Discoveries
Home > Molecular Oncology > Discoveries
Research unit director
Discoveries

Discovery that the CD4 and CD8 T-cell surface antigens are associated with the Src-related protein tyrosine kinase Lck (Cell, 1988), and that Lck is implicated for the initiation of T-cell receptor-mediated T-cell activation (Nature, 1989; Nature, 1991). A similar role in T-cell receptor signalling was ascribed to FynT, another Src-related enzyme found in T-cells (J. Exp. Med., 1991).

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Discovery that the protein tyrosine kinase Csk is a crucial component of the inhibitory machinery suppressing T-cell activation, as a result of its capacity to inactivate Src family kinases (Nature, 1993). This function requires the association of Csk with PTPN22/Lyp/PEP, a protein tyrosine phosphatase also implicated in the inhibition of T-cell activation (The EMBO Journal, 1996; J. Exp. Med., 1999). It is of note that polymorphisms in PTPN22/Lyp/PEP that interfere with the ability of the phosphatase to associate with Csk are strongly linked to susceptibility to auto-immune diseases in humans.

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Discovery that the adaptor molecule SAP, which is mutated in X-linked lymphoproliferative (XLP) disease in humans, plays a critical role in immune regulation by promoting, through a unique and novel signalling mechanism, the recruitment of Src-related protein tyrosine kinase FynT to the SLAM family of immune cell-specific receptors (Nature Immunology, 2001; Nature Cell Biology, 2003; Immunity, 2004).

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Discovery that SAP family adaptors are essential for the capacity of natural killer cells to kill abnormal hematopoietic cells (Nature Immunology, 2009).

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Discovery that the protein tyrosine phosphatase PTP-PEST is a positive regulator of immune cell functions, through its capacity to control the extent of tyrosine phosphorylation of molecules regulating the cellular cytoskeleton (Immunity, 2010).

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