Carien Niessen

FM | Department Cell Biology of the Skin (UHC) & CMMC

Prof. Dr. Carien Niessen CECAD Cologne
Prof. Dr. Carien Niessen

CECAD Scientific Coordinator
Principal Investigator

Research Areas

Cell and Tissue Architecture in health and Disease

The purpose of our research is to understand how cell shape controls the formation and (dys)function of barrier-forming epithelia like the skin epidermis.  Aging reduces skin barrier function and alters the mechanics and architecture of the epidermis.

Research Focus

The multilayered skin epidermis protects organisms from dehydration and against external challenges, such as mechanical insults, sun damage and microbes. To guarantee life-long barrier function, basal proliferation is balanced with tightly controlled suprabasal differentiation and cell shape change programs. Using a combination of genetics, high resolution imaging, proteomics, genomics and biophysical approaches, we address how adhesion, mechanics and signaling coordinate shape, fate and position of cells to make and regenerate a functional barrier. We also ask how uncoupling of these processes affect aging and cause inflammatory skin diseases or cancer.

Understanding how aging reshapes tissue architecture to promote disease may open up novel therapeutic opportunities for aging-associated diseases.

Our Goals

Our long-term goal is to gain a fundamental understanding of the molecular mechanisms that drive polarization in multi-layered epithelia to coordinate cell fate, growth, and innate immunity with cell and tissue architecture. This will be central for understanding how stem cells balance self-renewal with differentiation to maintain proper barrier function during normal tissue turnover, and how this balance is restored upon insults/damage to the tissue to prevent disease.

We aim to understand how the epidermis makes and maintains spatially distinct fate compartments, how single cells overcome these fate boundaries to regenerate a functional barrier, and why these are ignored in disease. We ask how cell adhesion and mechanics control these boundaries. We have shown that local dynamics in adhesion mechanics control cell shape changes necessary to functionally make and renew the barrier, while also protecting it from mechanical stress. We also explore how biochemical signals cooperate with adhesion to coordinate stem cell renewal with differentiation, identifying key roles for lipid homeostasis in barrier maintenance to counteract inflammatory disease. Altered tissue architecture is also a hallmark of cancer. We thus investigate how biomechanical signals affect carcinogenesis. Our work shows that known oncogenes/tumor suppressors synergize with regulators of mechanics to either drive or inhibit skin cancer linked to inflammation. We are now exploring the role of cell shape and fate in inflammation and cancer.

Our group combines mouse models with 2D and 3D cell culture models to explore mechanistic insights into control of cell and tissue structure. With the help of state-of-the-art (life) imaging, these models allow the scientists to address the impact of interfering with the cyto-architecture of cells and tissues on the formation, maintenance and restoration of the epidermal barrier, and follow the individual fate of cells. We combine this with phospho-proteomics and genome-wide analyses to identify downstream mechanisms that in the long run may potentially serve as therapeutic targets.

Our team has provided important contributions to identify external and internal cues that control stem cell fate decisions in the epidermis likely through regulation of oriented cell division that promote either renewal or differentiation. These results not only provide cues for how stem cell behavior is altered in aged or diseased skin, but might open up novel therapeutic possibilities to rejuvenate stem cells in these conditions in the long term. Moreover, the Niessen laboratory has made significant advances in the molecular circuitry through which cadherins control the polarization and integrity of the epidermal barrier. This provides new insight into how interference with adhesion or polarity complex building blocks result in cancer and in autoimmune, genetic, and inflammatory diseases in the skin and other epithelial tissues.

Open Positions

We have open PHD/Post-Doc positions! 
If you are enthusiastic about skin research and interested in joining our laboratory, please contact Prof. Carien Niessen or Dr. Gladiola Goranci-Buzhala.

Key Publications


  1. Kasper JY, Laschke MW, Koch M, Alibardi L, Magin T, Niessen CM, Del Campo A. (2024) Actin-templated Structures: Nature's Way to Hierarchical Surface Patterns (Gecko's Setae as Case Study). Adv Sci 11. doi: 10.1002/advs.202303816.
     
  2. Niessen CM, Manning ML, Wickström, SA. Mechanochemical principles of epidermal tissue dynamics. Cold Spring Harbor Perspectives in biology “Physical forces in biological systems” Jun 10. doi: 10.1101/cshperspect.a041518.
     
  3. Rübsam M, Püllen P, Tellkamp F, Bianco A, Pescoller M, Bloch W, Green KJ, Merkel R, Hoffmann B, Wickström SA, and Niessen CM. (2023) Polarity signaling balances epithelial contractility and mechanical resistance. Scientific Reports May 12;13(1):7743. doi: 10.1038/s41598-023-33485-5.
     
  4. Goranci-Buzhala G, Niessen CM. (2023) Calling long distance: Cell cycle-dependent Ca2+ flows connect stem cells across regeneration tissues. J Cell Biol. 2023 Jul 3;222(7). doi: 10.1083/jcb.202305022. Epub 2023 Jun 14.
     
  5. Koester J, Miroshnikova Y, Ghatak S, Chacón-Martínez C, Morgner J, Li X, Atanassov I, Altmuller J, Birk DE, Koch M, Bloch W, Bartusel M, Niessen CM, Rada-Iglesias A, and Wickström S. (2021) Niche stiffening compromises stem cell potential during aging by reducing chromatin accessibility at bivalent promoters. Nature Cell Biology 23:771-781. doi: 10.1038/s41556-021-00705-x.
     
  6. Peters F*, Tellkamp F*, Brodesser S, Wachmuth E, Tosetti B, Karow U, Bloch W, Utermohlen O, Krönke M, Niessen CM. (2020) Murine epidermal Ceramide Synthase 4 is a key regulator of skin barrier homeostasis. J Investig Derm. doi.org/10.1016/j.jid.2020.02.006.
     
  7. Nava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, Vihinen H, Jokitalo E, García Arcos JM, Hoffmann B, Merkel R, Niessen CM, Dahl KN, and Wickström SA. (2020) Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell 181:800-817.e22. doi: 10.1016/j.cell.2020.03.052.
Prof. Dr. Carien Niessen CECAD Cologne
Prof. Dr. Carien Niessen

CECAD Scientific Coordinator
Principal Investigator

Research Areas