Karsten Bach

Department of Pharmacology

With funding from the Cambridge Cancer Centre I have recently completed an interdisciplinary PhD project between the Marioni and Khaled lab at the University of Cambridge. During my PhD I utilized single-cell RNA sequencing to study how breast tissue changes during tumour development in genetically engineered mouse models. This has allowed me to identify the earliest cellular changes that occur before a visible tumour forms. We found that during tumourigenesis, a cell type referred to as alveolar cells, expands. In normal physiology, alveolar cells produce and secrete the constituents of milk during pregnancy and lactation. Thus, they only exist when induced by the presence of pregnancy hormones. However, we found that upon the loss-of-function of a gene called BRCA1, progenitor cells aberrantly give rise (i.e. differentiate) to these cells.

This work offers an explanation as to why the breast is particularly susceptible to tumour development in women with pathologic variants of BRCA1. We are currently investigating the utility of these findings in monitoring and preventing tumour development in these women.