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Metabolism

The research interests of our group are aimed towards a molecular understanding of how metabolism underpins cellular processes and influences cell-fate decisions in the context of ageing, cellular stress, and disease. In particular, we are interested in how metabolic heterogeneity arises within the same cell type, how metabolic fluxes sustain or remodel cellular identity, and how these processes may drive pathological states such as cancer.

To address these questions, we employ a broad range of metabolic approaches, including mass spectrometry, imaging, and flow cytometry, complemented by emerging biosensor technologies that allow real-time monitoring of metabolite fluxes with high spatiotemporal resolution.

A long-term goal of our research is to identify metabolic pathways that can be leveraged for therapeutic intervention, with the aim of improving tissue homeostasis, disease outcomes, and ultimately, human health-span.

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Picture taken using HYlight vector (FBP sensor)

(Koberstein, J. N., Stewart, M. L., Smith, C. B., Tarasov, A. I., Ashcroft, F. M., Stork, P. J., & Goodman, R. H. (2022). Monitoring glycolytic dynamics in single cells using a fluorescent biosensor for fructose 1, 6-bisphosphate. Proceedings of the National Academy of Sciences, 119(31), e2204407119.)

Epigenetics

Our research on epigenetics aims to understand how dynamic changes in metabolic pathways and metabolites alter gene expression, ultimately shaping processes from development to ageing. A particular focus is on how central metabolites such as acetyl-CoA, NAD⁺, or S-adenosylmethionine act as substrates or cofactors for chromatin modifications, thereby providing a direct mechanistic link between cellular metabolism and the epigenetic landscape.

We primarily employ CUT&RUN and CUT&Tag to interrogate disease models and distinct cell states, such as hypoxia, and ask how the chromatin landscape responds to shifts in metabolic flux. Of particular interest is how metabolic decline with age or under stress leads to measurable epigenetic changes that impair cellular function, and how targeted metabolic interventions might restore homeostasis.

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