Epithelial plasticity, regeneration, and tissue dynamics

This research theme focuses on how epithelial stem cells dynamically adapt their identity, renewal capacity, and differentiation potential during tissue remodelling, regeneration, and early tumorigenesis.

Using integrative approaches combining lineage tracing, single-cell transcriptomics, chromatin accessibility profiling, intravital imaging, organoid systems, and computational modelling, these studies uncovered how mechanical forces, extracellular matrix composition, and regenerative signalling pathways regulate epithelial cell-state transitions in vivo.

A central aspect of this work investigated how tissue mechanics and extracellular matrix stiffness influence epithelial stem cell competence and lineage plasticity. These studies demonstrated that epithelial stem cells transiently acquire regenerative and hybrid cellular states in response to stretching, wound repair, oncogenic stress, and changes in tissue architecture.

Together, these projects reveal how epithelial tissues dynamically transition between stable and plastic states during regeneration and disease, uncovering the molecular and biomechanical mechanisms controlling tissue adaptation and stem cell behaviour.

Selected studies

Mechanisms of stretch-mediated skin expansion at single-cell resolution

Nature (2020)
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Using lineage tracing, quantitative modelling, single-cell RNA sequencing, and chromatin profiling, this study demonstrated how mechanical stretching induces transient changes in epidermal stem cell renewal dynamics to promote tissue expansion in vivo. Stretching generated distinct basal cell populations with differential regenerative behaviours and revealed gene-regulatory networks activated during mechanically induced tissue remodelling.

Dynamic regulation of tissue fluidity controls skin repair during wound healing

Cell (2024)
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This work uncovered how epithelial tissues dynamically transition between solid-like and fluid-like states during wound repair. Combining intravital imaging, lineage tracing, single-cell transcriptomics, and epigenetic profiling, the study identified a regenerative programme controlled by the EGFR/AP1 axis that promotes stem cell activation and tissue remodelling during re-epithelialisation.

Collagen signaling and matrix stiffness regulate multipotency in glandular epithelial stem cells in mice

Nature Communications (2024)
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This study demonstrated that extracellular matrix stiffness and Collagen I signalling regulate the reactivation of multipotency in adult glandular basal stem cells. Using organoid systems and single-cell RNA sequencing, the work identified activation of the β1 integrin/FAK/AP-1 axis as a key regulator of mechanically induced lineage plasticity in mammary gland and prostate epithelia.

Survivin Promotes Stem Cell Competence for Skin Cancer Initiation

Cancer Discovery (2025)
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This study identified Survivin as a key regulator controlling the competence of epidermal stem cells to initiate basal cell carcinoma. Using transcriptional profiling and genetic mouse models, the work demonstrated how Survivin promotes stem cell survival, self-renewal, and resistance to differentiation, thereby enabling oncogene-expressing stem cells to initiate tumour formation.

Highlights

• Mechanical forces dynamically regulate epidermal stem cell renewal and tissue expansion.
• Tissue repair involves transient transitions between solid-like and fluid-like epithelial states.
• Extracellular matrix stiffness and collagen signalling regulate epithelial stem cell multipotency.
• Regenerative programmes are associated with dynamic chromatin and transcriptional state transitions.
• Mechanical and regenerative signalling pathways contribute to lineage plasticity and tumour initiation.
• Single-cell and multi-omics approaches uncover transient hybrid and regenerative epithelial states in vivo.

My contribution

I contributed to the computational analysis of bulk and single-cell transcriptomic datasets, chromatin accessibility profiling, trajectory inference, and regulatory network analyses associated with epithelial plasticity, tissue remodelling, and regenerative cell-state transitions. My work also involved integrating multi-omics datasets to characterise how mechanical stress, extracellular matrix signalling, and regenerative programmes regulate epithelial stem cell behaviour during tissue repair and tumour initiation.