Tracking clonal diversity during breast cancer development

• PhD

Breast cancer is a heterogeneous disease, with a high degree of diversity between and within tumours. Although breast cancer can be stratified into different subtypes, the clonogenicity and invasive potential of various cellular subsets within the tumour remain to be determined. Primary tumours are hierarchically organised entities, sustained by a highly tumorigenic population of cancer-initiating cells. This project aims to determine the clonal diversity within breast tumours, and to understand how a single cell contributes to tumour progression by determining its expression profile. This study will involve three-dimensional imaging of tagged cells (Rios, Cancer Cell 2019 35(4); Merino, Nat Comms 2019 10 (766)) during the different stages of breast carcinogenesis to investigate clonal evolution in the context of tumour behaviour.

The Visvader/Lindeman Laboratory (ACRF Cancer Biology and Stem Cells Division) has a strong background in mammary gland biology and translational breast cancer research that has led to clinical trials. Our group’s contributions to the field include definition of the mammary gland hierarchy (eg Nature 2006, 2010, 2014; Nature Cell Biol 2007, 2020; Nature Comms 2016, 2017; Cancer Cell 2019; EMBO J 2021); identification of the cell-of-origin of breast cancer (Nature Medicine 2009, 2016); establishment of pre-clinical models and clinical trials (Cancer Cell 2013; Cancer Discovery 2019; Clin Cancer Res 2020, 2022). We routinely exploit in vivo models (including lineage tracing and patient-derived xenograft models), single-cell studies, flow cytometry, CRISPR-Cas9 genomic editing and screens, high resolution 3D imaging and genomics.