Department of cell biology & CECAD

Research Area

The Niessen laboratory aims at understanding how regulation of cell structure determines the shape and function of epithelial barriers. We ask how regulators of cell architecture integrate with signals that control metabolism, inflammation and growth to control the formation and maintenance of the multilayered epidermal skin barrier and how alterations in these biomechanical networks result in disease.

Research Projects

Top Figure. Rainbow mouse epidermis (Christian Jüngst, Imaging Facility CECAD) Bottom Figure. Multilayered epidermis and layer specific protein expression (Adapted from Rübsam et al., 2017).
Top Figure. Rainbow mouse epidermis (Christian Jüngst, Imaging Facility CECAD) Bottom Figure. Multilayered epidermis and layer specific protein expression (Adapted from Rübsam et al., 2017).

Intercellular adhesion and cell polarity are crucial determinants of tissue morphogenesis and architecture. In contrast to apico-basolateral polarity in simple epithelia, multi-layered epithelia polarizes not within a single cell but across layers. How regulation of cell adhesion and cell shape contributes to the formation and life-long regeneration of multi-layered epithelial barriers, such as the skin epidermal barrier, is only poorly understood. The skin epidermis protects organisms from dehydration and against external challenges such as mechanical insults, UV radiation and micro-organisms. A dysfunctional epidermal barrier is linked to a range of skin diseases.

Using a combination of mouse genetics, high resolution imaging, proteomics and biophysical approaches we address at different scale lengths how regulation of cell shape, cell fate and positioning of cells are coordinated to form, maintain and restore a functional skin epidermal barrier. We also investigate how disturbed coordination of these processes promote barrier dysfuntion and cause diseases such as inflammatory skin diseases as well as skin cancer. 

Ongoing projects in the laboratory are: 
(1) understanding how cell adhesion and cell mechanics regulate epidermal differentiation and barrier formation (2) deciphering the role of polarity signaling in cell division, cell fate, cell mechanics, in epidermal development, homeostasis and skin cancer  (3) address how metabolic pathways, including lipid signaling and insulin/IGF-1 signaling regulate skin barrier function and stem cell dynamics and whether altered metabolic signaling in the skin promotes type II diabetes as well as its associated diseases in the skin.

Our interdisciplinary research profits from fantastic collaborators coming from dermatology, cell biology, mechanobiology, soft matter physics, theoretical physics, chemical engineering, metabolism research, and infectiology.

Group Members

Selected Publikationen

Nava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, Vihinen H, Jokitalo E, Li X, García Arcos YN, Hoffmann B, Merkel R, Niessen CM, Dahl KN, and Wickström SA. Heterochromatin-Driven Nuclear Softening Protectsthe Genome against Mechanical-Stress-Induced Damage. Cell. 2020 Apr 9. 181, 1–18. DOI: 10.1016/j.cell.2020.03.052

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. Invest Dermatol, doi.org/10.1016/j.jid.2020.02.006* shared first authors

Miroshnikova YA, Le HQ, David Schneider D, Thalheim T, Rübsam M, Bremicker N, Polleux J, Kamprad N, Tarantola M, Wang I, Balland M, Niessen CM, Galle J, Wickström  SA (2018) A biomechanical network of adhesion forces and cell mechanics couples proliferation and differentiation to drive epidermal stratification. 
Nature Cell Biology, 20:69-80. doi: 10.1038/s41556-017-0005

Shafraz O*, Rübsam M*, Stahley SN, Caldara AL, Kowalczyk AP, Niessen CM, Sivasankar S (2018) E-cadherin binds to desmoglein to facilitate desmosome formation. Elife, 12;7:e37629. doi: 10.7554/eLife.37629 *shared first authors

Vorhagen S**, Kleefisch D*, Persa, O-D, Graband, A, Schwickert A, Saynisch M, Leitges M, Niessen CM#, and Iden S# (2018) Shared and independent functions of aPKCλ and Par3 in skin tumorigenesis. Oncogene, 37:5136-5146. doi: 10.1038/s41388-018-0313-1 *shared first and #shared corresponding last authors

Wickström SA, and Niessen CM (2018) Cell adhesion and mechanics as drivers of tissue organization and differentiation:  a question of local symmetry breaking. Curr Opin Cell Biol, 54:89-97. doi: 10.1016/j.ceb.2018.05.003.

Rübsam M, Mertz AF, Kubo A, Marg S, Jüngst C, Goranci-Buzhala G, Schauss AC, Horsley V, Dufresne E, Moser M, Ziegler W, Amagai M, Wickström SA and Niessen CM (2017) E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and Tight Junction positioning. Nat Commun, 8:1250. doi: 10.1038/s41467-017-01170-7

Quang Le H, Ghatak S, Yeung CYC, Tellkamp F, Gunschmann C, Dieterich C, Yeroslaviz A, Habermann B, Pombo A, Niessen CM, Wickström S (2016) Mechanical regulation of transcription drives Polycomb mediated gene silence during lineage committment. Nat Cell Biol, 18(8): 864-75. doi: 10.1038/ncb3387.

Peters F, Vorhagen S, Brodesser S, Jacobshagen K, Brüning JC, Niessen CM#, Krönke M# (2015) Ceramide synthase 4 regulates stem cell homeostasis and hair follicle cycling. J Invest Dermatol 135(6): 1501-9. doi: 10.1038/jid.2015.60. *co-corresponding authors

Guenschmann C, Stachelscheid H, Akyüz MD, Schmitz A, Missero C, Brüning JC#, Niessen CM# (2013) Insulin/IGF-1 controls epidermal morphogenesis via regulation of FoxO-mediated p63 inhibition. Dev Cell, 26(07): 176-87. doi: 10.1016/j.devcel.2013.05.017.

Niessen MT, Scott J, Zielinski J, Vorhagen S, Blanpain C, Leitges M, Niessen CM (2013) aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation. J Cell Biol, 16(09) 202: 887-900. doi: 10.1083/jcb.201307001.

*Shared first authorship
#Shared corresponding authorship

Publications Prof. Dr. Carien Niessen (PubMed)

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