Protein-protein interactions. Contributions to landmark papers describing the mechanisms of interaction between tyrosine-phosphorylated growth factor receptors and SH2/SH3-containing intracellular signaling molecules (Embo J, Mol Cell Biol, Proc Natl Acad Sci U S A).
Identification of JAG1 as a novel prognostic marker in breast cancer. JAG1 is a ligand that activates a signaling pathway (Notch signaling cascade) that can be directly targeted with anti-Notch compounds such as γ-secretase inhibitors (GSI). In this work we showed that JAG1 is an independent predictor of outcome, even in patients who have traditionally been identified as having “good” prognosis (i.e. axillary lymph node-negative patients). Furthermore, JAG1 expression identifies patients with breast tumors of the triple negative (TN) subtype for whom there are currently no targeted therapies available. These findings make the Notch signaling pathway an attractive therapeutic target in TN breast cancer. As such, we have been involved in clinical trials to test anti-Notch compounds in cancer (Cancer Research, Gynecol Oncol, Br J Cancer, Invest New Drugs).
High throughput kinase inhibitor screens to identify drivers of Notch activation in breast cancer. In this work we have identified the TRB3 and MAPK-ERK/TGFβ pathways as fundamental Notch regulators in breast cancer (Proc Natl Acad Sci U S A).