Fat tissue differs widely in its ability to store lipids and adapt to metabolic stress. These properties—known as adipocyte plasticity—strongly influence whether individuals with obesity develop complications such as insulin resistance. However, genetic factors alone cannot explain this variability. Growing evidence shows that epigenetic mechanisms, particularly DNA methylation (DNAm), help regulate fat cell function, yet this knowledge has not been translated into targeted therapeutic approaches.

The applicant’s previous research has identified DNAm patterns that vary between fat depots, across degrees of obesity, and before and after weight loss. Her work has also shown that biological aging contributes to changes in body fat regulation and that targeted DNAm modifications may influence lipid storage. Despite these advances, the cell-type-specific role of DNAm in adipocyte and adipose tissue function—and its potential for therapeutic use—remains poorly understood.

The proposed project therefore aims to clarify how DNAm in distinct fat cell types shapes adipocyte plasticity and metabolic health. First, the applicant will generate a detailed cell-specific DNAm atlas of human fat depots to identify epigenetic features linked to metabolic outcomes and age-related dysfunction. She will then apply CRISPR–dCas9-based epigenetic reprogramming to precisely modify DNAm at selected sites in human 2D and 3D adipose models, enabling direct testing of whether such targeted changes improve metabolic responses.

This research will provide essential insights into the epigenetic control of fat cell biology and lay the foundation for future tissue-specific therapeutic strategies to reduce metabolic dysfunction and the health burden of obesity.