Dr. Kate Miroshnikova
ECM mechanics and nuclear mechanotransduction in genome integrity and cell state regulation
Cell Biology / Molecular Biology
Cell Mechanics
Stem Cell Biology
Mechanobiology
Colorectal cancer
Cells are continuously exposed to a range of biomechanical forces emanating from their dynamic, topologically complex microenvironments. Recent work implicates mechanical forces as critical mediators of several key processes from organogenesis to adult stem cell specification and maintenance, to cancer progression, degenerative diseases, and aging. We aim to uncover the mechanisms by which cells sense and integrate biochemical and biophysical cues from their environments to make decisions with respect to their state/fate. Our work suggests that nuclear deformation and physical and architectural properties of the nuclear periphery play a central role in this process. Using cutting-edge, interdisciplinary approaches we aim to understand the role of forces imposed on the tissue by its microenvironment and nuclear mechanotransduction in modulating genome architecture and gene expression patterns to tune stem cell fate. Our favorite model systems are 3D patient-derived colonic organoids and mouse models of colorectal cancer, 2- and 3D models of human induced pluripotent stem cells, and advanced 2D human epithelial cell monolayer systems which we combine with a number of flow/stretch/compression/confinement bioreactors and microfluidic approaches amenable to quantitative live cell imaging.
Vita
- 2005 - 2009 BS in Engineering, FW Olin College of Engineering, Needham MA USA
- 2009 - 2015 PhD in Biomedical Engineering, UC Berkeley and UC San Francisco CA USA
- 2015 - 2017 Whitaker Postdoctoral Fellow at the Institute for Advanced Biosciences,
in Grenoble, France - 2017 – 2019 EMBO Postdoctoral Fellow at MPI for Biology of Ageing in Cologne, Germany
- 2019 – 2021 HSFP Postdoctoral Fellow at the University of Helsinki, Helsinki, Finland
- 2021 – 2025 Stadtman Tenure Track Investigator at the NIDDK/NIH, Bethesda USA
- 2025 – present Max Planck Research Group Leader (W2) at the Max Planck Institute for
Molecular Biomedicine, Münster, Germany
Selected references
Hervé S, Scelfo A, Bersano-Marchisio G, Grison M, Vaidziulyte K, Deygas M, Nader G, Mace A-S, Gentili M, Williart A, Manel N, Piel M, Miroshnikova YA* (co-last/co-corresponding), Fachinetti*. (2025). Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint. Nat Cell Biol. 2025 Jan;27(1):73-86.
McCreery K, Stubb A, Stephens R, Cook A, Kruse K, Lackmann J, Niessen CM, Biggs LC, Nykänen S, Zou J, Vuoristo S, Miroshnikova YA* (co-last/co-corresponding), and Wickström SA*. (2025) Mechano-osmotic signals control chromatin state and exit from pluripotency. https://www.biorxiv.org/content/10.1101/2024.09.07.611779v1
Koester, J., Miroshnikova YA, Ghatak S, Andrés Chacón-Martínez C, Li X, Atanassov I, Altmüller J, Birk DE, Iglesias M, Wickström SA. (2021)vNiche stiffening compromises hair follicle stem cell potential during ageing by reducing bivalent promoter accessibility. Nat Cell Biol. 2021 Jul;23(7):771-781.
Nava MM and Miroshnikova YA (co-first), Biggs LC, Whitefield DB, Vihinen H, Jokitalo E, García Arcos JM, Hoffmann B, Merkel R, Niessen CM, Noel Dahl K, and Wickström S.A. (2020) Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell 2020 May 14;181(4):800817.
Miroshnikova YA, Le HQ, Schneider, D, Thalheim T, Rübsam M, Bremicker N, Polleux J, Kamprad N, Tarantola M, Wang I, Balland M, Niessen CMN, Galle J, and Wickström SA. A biomechanical network of adhesion forces and cell mechanics couples proliferation and differentiation to drive epidermal stratification. (2018) Nat Cell Biol 2018 Jan;20(1):69-80.
Links
Miroshnikova Lab
The lab is moving to the MPI in summer 2025.