Molecular Wound Healing Lab
Karolinska Institute
Research profile
Decoding the molecular logic of wound repair and radiation injury to develop next-generation therapies.
We study how human skin repairs itself after injury — and why this process sometimes fails. Wound healing is a fundamental biological program, yet chronic wounds remain a major medical challenge, affecting millions of patients worldwide and lacking effective treatments. Our lab seeks to decode the molecular logic of skin repair, uncover why healing goes awry in chronic wounds and after cancer radiotherapy, and translate these insights into new therapeutic strategies.
Our research spans four interconnected themes:
1. Molecular atlas of human wound healing
We are building the first comprehensive, spatiotemporal molecular map of human skin repair. Through multimodal single-cell and spatial transcriptomics of acute and chronic wounds, we chart how diverse cell types coordinate across the phases of healing — and why this process sometimes fails in chronic conditions such as pressure ulcers. In parallel, we have performed bulk RNA sequencing to profile long non-coding RNA, microRNA, and circular RNA expression in human acute and chronic wound samples. Together, these datasets provide a multi-layered view of gene regulation in wound biology. Our interactive wound atlas (link) makes these data publicly accessible as a community resource, enabling broad exploration of human wound biology.
Related publications: Liu Z, Bian X, Luo L, Björklund ÅK, Li L, Zhang L, Chen Y, Guo L, Gao J, Cao C, Wang J, He W, Xiao Y, Zhu L, Annusver K, Gopee NH, Basurto-Lozada D, Horsfall D, Bennett CL, Kasper M, Haniffa M, Sommar P, Li D, Xu Landén N. Spatiotemporal single-cell roadmap of human skin wound healing, Cell Stem Cell, 2024, PMID: 39729995 Liu Z*, Zhang L*, Toma MA, Li D, Bian X, Pastar I, Tomic-Canic M, Sommar P, Xu Landén N. Integrative small and long RNA omics analysis of human healing and nonhealing wounds discovers cooperating microRNAs as therapeutic targets. eLife, 2022, PMID: 35942686 Toma MA*, Liu Z*†, Wang Q, Zhang L, Li D, Sommar P, Xu Landén N. Circular RNA signatures of human healing and non-healing wounds. Journal of Investigative Dermatology, 2022. PMID: 35429518 Li D, Cheng S, Pei Y, Sommar P, Kärner J, Herter EK, Toma MA, Zhang L, Pham K, Cheung YT, Liu Z, Chen X, Eidsmo L, Deng Q, Landén NX. Single-cell analysis reveals MHCII expressing keratinocytes in pressure ulcers with worse healing outcomes. Journal of Investigative Dermatology, 2021. PMID: 34536485.
2. Regulatory RNAs in skin repair
We focus on non-coding RNAs (ncRNAs) — including microRNAs, long non-coding RNAs, and circular RNAs — as key regulators of wound healing. These molecules are highly cell-type specific and evolve rapidly, making them promising therapeutic targets. Using patient-derived wound tissues, advanced single-cell and spatial transcriptomics, and functional models, we map how ncRNAs control the cellular choreography of repair. Our work has identified multiple ncRNAs with central roles in tissue regeneration, and we have demonstrated their therapeutic potential in preclinical wound models.
Related publications: Niu G, Toma MA, Geara J, Bian X, Chen Y, Luo L, Wang Q, Xiao Y, Vij M, Piipponen M, Liu Z, Oasa S, Zhang L, Schlesinger D, Végvári Á, Li D, Wang A, Vukojević V, Elsässer SJ, Sommar P, Xu Landén N. Collaborative Duality of CircGLIS3(2) RNA and Protein in human Wound Repair, Advanced Science, 2025, PMID: 40279507 Li D, Liu Z, Zhang L, Bian X, Wu J, Li L, Chen Y, Luo L, Pan L, Kong L, Xiao Y, Wang J, Zhang X, Wang W, Toma M, Piipponen M, Sommar P, Xu Landén N. The lncRNA SNHG26 drives the inflammatory-to-proliferative state transition of keratinocyte progenitor cells during wound healing. Nature Communications, 2024, PMID: 39366968 Wang Q, Niu G, Liu Z, Toma MA, Geara J, Bian X, Zhang L, Piipponen M, Li D, Wang A, Sommar P, Xu Landén N. Circular RNA circASH1L(4,5) protects microRNA-129-5p from target-directed microRNA degradation in human skin wound healing. British Journal of Dermatology. PMID: 39422230 Zhang L, Piipponen M, Liu Z, Li D, Bian X, Liu G, Geara J, Toma M, Sommar P & Xu Landén N. Human skin specific long noncoding RNA HOXC13-AS regulates epidermal differentiation by interfering with Golgi-ER retrograde transport. Cell Death & Differentiation, 2023, PMID: 36869179 Li D, Kular L, Vij M, Herter EK, Li X, Wang A, Chu T, Toma M-A, Zhang L, Liapi E, Mota A, Blomqvist L, Gallais Sérézal I, Rollman O, Wikstrom JD, Bienko M, Berglund D, Ståhle M, Sommar P, Jagodic M, Xu Landén N. Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration. Proc Natl Acad Sci U S A, 2019. PMID: 31019085.
3. RNA-based regenerative therapies
Building on our mechanistic discoveries, we are developing therapeutic strategies that integrate molecular pharmacology, RNA biology, and regenerative medicine. Our goal is to translate regulatory RNA discoveries into treatments for hard-to-heal wounds.
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ncRNA-targeted therapies: We design and test antisense oligonucleotides, mimics, and inhibitors in advanced human ex vivo and murine wound models. These preclinical studies aim to correct pathological RNA programs and accelerate wound closure under clinically relevant conditions, such as diabetes and ischemia.
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ncRNA-enhanced cell therapy: We explore how transient modulation of regulatory RNAs can preserve stemness and improve the regenerative capacity of cultured keratinocytes used in skin grafting. This approach has the potential to yield next-generation cell therapies optimized for treating chronic wounds.
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Delivery platforms: In collaboration with bioengineers, we are advancing topical and targeted delivery systems for therapeutic RNAs, ensuring safety, stability, and clinical feasibility.
This line of research aims to deliver RNA-based wound therapies ready for clinical development, bridging fundamental discovery with regenerative medicine applications.
Related publications: Li D*, Wang A*, Liu X, Meisgen F, Grünler J, Botusan IR, Narayanan S, Erikci E, Li X, Blomqvist L, Du L, Pivarcsi A, Sonkoly E, Chowdhury K, Catrina SB, Ståhle M and Xu Landén N. MicroRNA-132 enhances transition from inflammation to proliferation during wound healing. Journal of Clinical Investigation, 2015. PMID: 26121747 Li X*, Li D*, Wang A, Chu T, Lohcharoenkal W, Zheng X, Grünler J, Narayanan S, Eliasson S, Herter EK, Wang Y, Ma Y, Ehrström M, Eidsmo L, Kasper M, Pivarcsi A, Sonkoly E, Catrina S-B, Ståhle M, Xu Landén N.. MicroRNA-132 with therapeutic potential in chronic wounds. Journal of Investigative Dermatology,2017. PMID: 28807666.
4. Radiation memory and late tissue injury
With improved cancer survival, long-term side effects of radiotherapy have emerged as a growing problem. We recently discovered that skin cells retain a long-lasting “radiation memory” — an epigenetic imprint that persists for years after treatment and impairs wound healing in cancer survivors. This breakthrough provides a molecular explanation for why radiotherapy causes late-onset adverse effects such as fibrosis and chronic ulcers. We now use state-of-the-art single-cell multi-omics profiling to dissect how radiation memory is established, maintained, and recalled. Ultimately, we aim to erase maladaptive radiation memory to restore tissue fitness and improve the quality of life for cancer survivors.
Related publications: Bian X, Piipponen M, Liu Z, Luo L, Geara J, Chen Y, Sangsuwan T, Maselli M, Diaz C, Bain CA, Eenjes E, Genander M, Crichton M, Cash JL, Archambault L, Haghdoost S, Fradette J, Sommar P, Halle M, Xu Landén N. Epigenetic memory of radiotherapy in dermal fibroblasts impairs wound repair capacity in cancer survivors. Nature Communications, 2024. PMID: 39468077
Our vision
By building a research platform that integrates molecular biology, advanced genomics, and direct access to patient materials, we bridge basic discovery with clinical need. Our goal is to transform treatments for chronic wounds and radiotherapy side effects by targeting hidden regulators of healing. Harnessing RNA networks and resetting radiation memory could redefine regenerative medicine and improve patients’ lives worldwide.