Imperial College London


Faculty of Natural SciencesDepartment of Life Sciences




kirsten.mcewen Website




316Sir Ernst Chain BuildingSouth Kensington Campus





Transcriptional heterogeneity

Heterogeneity is emerging as a key determinant of health and disease. The proposed functions of heterogeneity range from controlling cell fate decisions, disease penetrance, drug resistance, and cancer metastasis. However, the molecular mechanisms regulating such processes remain unknown. Our research aims to identify the mechanisms and consequences of transcriptional heterogeneity to learn how to improve disease outcomes.

Genetics and disease

Genetics is a significant determinant of human health and disease, yet it remains a major challenge to define the molecular processes linking genotype to phenotype. By starting with a simple genetic system, we can address this challenge and apply the knowledge gained to understand more complex genetic mutations.

Part of our research focuses on a class of recessive genetic mutations that result in the loss of one gene copy. In special cases, the remaining gene copy is insufficient and this leads to disease. These ‘haploinsufficient’ mutations can arise before birth and cause congenital disorders, or they can appear throughout our lifetime and contribute to the development of cancer. Discovering the molecular consequences of haploinsufficiency is critical for the development of successful treatments for these severe diseases. Our goal is to identify the molecular changes and discover how to manipulate these to restore a healthy state.

Environmental perturbations

Molecular mechanisms link the genome to phenotypic consequences and are key to interpret biological processes and guide effective therapies. Environmental interactions can modulate these biological processes in unexpected ways.

We use a powerful stem cell model system to discover the molecular mechanisms impacting cell function. Undertaking large-scale molecular profiling of pluripotent stem cells after manipulation of environmental growth conditions has led to new insights in gene regulation. Epigenetic changes are induced by changes to growth media and this has enabled us to discover control mechanisms of dynamic DNA methylation in stem cells. Environmental modulation impacts cellular heterogeneity and we have identified the molecular mechanisms responsible by integrating computational analysis with single-cell transcriptional profiling. These findings have implications for assisted reproductive technologies, regenerative medicine and drug testing.