Researchers in Conversation: Ifigeneia Kalampouka and Khalid Akram/ Aysha Ali and Yumeng Yang

Breast Cancer is the most diagnosed malignancy worldwide and the leading cause of mortality in women. Large-scale genomic studies have revealed significant chromosomal changes in breast cancer, importantly copy number variation and point mutations that drive tumourigenesis and alter therapeutic responses. However, the mechanisms by which exogenous genotoxic stressors induce vulnerabilities at distinctive genomic landscapes are not fully understood.

Utilizing a unique gene-edited model created at the Genome Engineering Laboratory at Westminster, we have attempted to analyse the mutation patterns underlying genomic instability, mutational processes linked to DNA replication stress using the DNA polymerase inhibitor, aphidicolin. Using language models trained on DNA sequencing data, we have obtained unique genome-wide variant and mutation patterns across chromosomes, including known fragile sites. This bioinformatics-powered approach enables a deeper understanding of mutational signatures, uncovering patterns that traditional pipelines may overlook. By analysing these mutational footprints across both wild-type and CRISPR-engineered MCF-7 cells, we reveal for the first time how external replication stressors reshape the genomic landscape, uncovering gene-specific susceptibilities that are amplified in the absence of key regulatory proteins such as ZFP36L1. Our study demonstrates how integrating CRISPR functional genomics with next-generation sequencing and computational biology tools can critically challenge static views of cancer progression, revealing hidden vulnerabilities that could shape future therapeutic strategies. In doing so, we advocate for a research paradigm that embraces complexity, questions reductionist interpretations, and envisions a more inclusive and dynamic future for cancer research.

Khalid Akram is a PhD researcher in Biotechnology at the University of Westminster, investigating the role of in genomic instability in breast cancer. His research focuses on CRISPR/Cas9 gene editing of cells, studying the effects of replication stress using, and analysing whole genome sequencing (WGS) data to identify mutations, fragile sites, and structural variations. Khalid integrates bioinformatics, cell culture, and mutation visualisation tools to explore cancer vulnerability and therapeutic targets. Passionate about accessible science, he also shares insights on CRISPR and cancer genomics through public engagement, aiming to bridge lab research with real-world impact.