The Wickström lab combines state-of-the-art scale-bridging technologies from nanoscale atomic force microscopy and next-generation sequencing to novel ex vivo tissue culture methods, the whole organism live imaging and in silico modeling all the way up to analysis of the clinical patient material. The research is highly interdisciplinary and involves collaborations with mathematicians, physicists, and clinical oncologists. Recent work from the Wickström group has uncovered how a generation of cellular forces is important for controlling stem cell fate and coordinating cell fate with cell position within the tissue. Furthermore, the laboratory has discovered how extrinsic forces generated by the tissue impact chromatin structure and epigenetic gene silencing, thereby controlling the transcriptional state and lineage commitment of stem cells. Read more about the ongoing projects below.
Recent Research Highlights
- Identification of mechanisms by which stem cell niche metabolism (Kim et al., Cell Metabolism 2020) and mechanical properties (Koester et al., Nat Cell Biol 2021) control hair follicle stem cell activation and plasticity.
- Discovery of how force induces calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin proximal to the nuclear lamina. The resulting changes in chromatin mobility, viscoelasticity, and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage (Nava, Miroshnikova et al. Cell 2020)
- Identifying the mechanistic principles that allow maintenance of a stratified epithelium through biomechanical coupling of cell division, differentiation and delamination (Miroshnikova et al., Nat Cell Biol 2018)
- Discovery of a novel mechanism by which mechanical force regulates nuclear architecture and chromatin structure, thereby affecting epigenetic silencing of epidermal stem cell lineage commitment genes (Le et al. Nat Cell Biol 2016)