Skin is the largest human organ and contains an intricate variety of cell types that assure proper tissue architecture and function, which includes barrier formation, thermoregulation and hair growth. An imbalance of cell types and/or molecular signalling often results in disease.
With our research – rooted within the fields of skin and stem cell biology – we aim to answer fundamental questions about tissue homeostasis, repair and regeneration. We use modern techniques such as single-cell transcriptomics, in vivo lineage-tracing, spatial mapping in situ and computational biology, to uncover the cellular behaviour and molecular signals of individual cells in skin during health, repair and cancer development, in order to understand skin disorders, improve early cancer detection and uncover new regenerative strategies to restore skin.
Ongoing research projects:
1. Decoding the molecular anatomy of skin. We just completed a molecular (scRNA-seq) and spatial (smRNA-FISH) cell atlas of mouse skin during hair growth and rest (Joost, Annusver et al. 2020), where we defined 56 cell types and states and uncovered how they coordinate hair growth. We also looked at progenitor commitment, lineage differentiation, spatiotemporal fibroblast heterogeneity, and potential epithelial-stromal interactions. Using the expertise and knowledge gained, we are expanding towards human skin analyses with the goal to generate a detailed cell atlas across the human body to propel our molecular understanding of skin in health and disease.
2. Identifying regulatory mechanisms controlling epithelial stem-cell activation and differentiation. We study when stem cells commit (“lock-in”) towards differentiation and if stem-cell activation can be controlled by non-epithelial cell types and cell-extrinsic niche factors, using in vivo lineage tracing and cell depletion, in utero gene knock down and computational analyses.
3. Improving skin restoration by studying wound healing and cancer initiation. We study how wounding or stromal micro-niches promote skin cancer formation. Building on these results we investigate how modulation of signalling pathways in the epithelium and stroma can shift a tumour fate into a developmental program.
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