Research

Research Overview.

  • Molecular mechanisms underlying intracellular signalling activated by the Wnt and Hedgehog families of secreted growth factors.

    Fully understand the molecular signalling mechanisms underlying the Wnt and Hedgehog pathways.
    We integrate cutting edge mass spectrometry-based proteomic technologies and genome-wide CRISPR genomic techniques with traditional biochemistry and cell biology approaches to further understand how the Wnt and Hedgehog pathways function, in different cellular contexts and how they become deregulated in diseases. Identification of new genes regulating these pathways, the post-translational modifications and epigenetics mechanisms impinging on pathway activity are also studied.

 

  • Development of new therapeutics targeting developmental¬†pathways.
    We have developed therapeutic antibodies inhibiting Wnt signalling that are now under clinical evaluation. We plan to continue optimize second generation molecules that are safer and more effective as well as identify novel antibodies that block new targets in the Wnt pathway. Recently, we also have developed a new antibody modality that enables activation of Wnt signalling pathways with complete selectivity. We are testing these molecules for regenerative medicine applications such asdirected differentiation of progenitor stem cells for cell therapies and direct mobilization of tissue stem cells for endogenous repair.

 

 

 

 

 

 

  • Deciphering the molecular wiring of high fatality cancers using functional genomic screens.
    Glioblastoma and pancreatic ductal adenocarcinomas are two cancers with especially poor prognosis. Using genome-wide CRISPR-Cas9 functional and phenotypic screens performed in patient-derived cancer stem cells, we are identifying genes that 1) are essential for the growth of these cancers 2) block their normal differentiation 3) underlie tumour heterogeneity. We are also performing chemogenomic screens to identify mechanisms of drug resistance and genes conferring hypersensitivity to standard of care therapeutic drugs.