Reconstructing the evolution of heterogeneous breast cancer

Breast tumours contain genetically and phenotypically distinct populations that do not respond uniformly to therapy. Some subclones survive treatment, interact with organ-specific stromal environments and acquire metastatic traits. The laboratory combines faithful heterogeneous tumour models with single-cell, proteomic and functional screens to reconstruct this evolution and identify vulnerabilities before resistant states become dominant.

HER2 heterogeneity and subclonal evolution

We reconstruct how HER2-high and HER2-low subpopulations compete, cooperate and change during targeted therapy.

Glycocalyx and stromal resistance

We investigate how stromal contact, glycoproteins and the cancer-cell glycocalyx shield HER2 signalling from targeted therapy.

Metastatic cascade and organ adaptation

We identify the programmes that enable dissemination, tissue entry and growth at distant metastatic sites.

Therapeutic vulnerability mapping

We combine multi-omic profiling and functional screening to find dependencies shared by resistant subclones or created during adaptation.