Sarah Aitken, MBChB, PhD

Among the most critical - and yet least understood - stages of cancer formation are the earliest. To address this, our lab seeks to understand the causes and consequences of DNA damage in human health and disease, and how the resultant mutations and genome instability contribute to tumourigenesis.

We recently discovered a phenomenon termed “DNA lesion segregation” (Aitken et al, Nature 2020) which explains how the persistence of DNA lesions though mitosis acts as an engine for genetic diversity and the creation of multiallelic variation in daughter cells. We found persistent DNA lesions in human cancer genomes, which are also ubiquitously present in human cell lines treated with a breadth of common environmental mutagens, including ultraviolet light, tobacco smoke (benzopyrene), and chemotherapeutics (temozolomide). More recently, it was shown that such DNA lesions can also persist in normal tissues for months to years. Understanding the resultant ubiquity of somatic mosaicism across our tissues has wide-reaching implications for normal embryonic development, healthy ageing, chronic disease, and cancer initiation and promotion.

Our multidisciplinary team of computational, experimental, and clinical scientists and collaborators is now applying genomic pathology approaches (combining molecular biology, genomics, and spatial transcriptomics) to model systems and primary human tissues.

Current projects include:

• How does the spatial distribution of mutations vary within tissues in patients with colorectal cancer?
• Can we predict genotype (mutation) from phenotype (histology)?
• How do DNA repair enzymes interact following chemotherapy exposure?
• How does genetic background influence tumourigenesis?
• Can we develop human-relevant models to test potential mutagens?