50 Years ESDR Anniversary Lecture 2: Cell biology
Title: How to build and regenerate a functional skin barrier
Date: Thursday 23 September 2021, 10.30.10.50
Carien Niessen is a Professor and head of the Department Cell Biology of the Skin at the University of Cologne. She did her PhD at The Netherlands Cancer Institute, Amsterdam and received her PhD in molecular cell biology from the University of Amsterdam in 1996. She received the Dutch Cancer Society fellowship award to do a postdoc at Memorial Sloan Kettering Cancer Center in New York, after which she became a junior group leader at the Center for Molecular Medicine Cologne at the University of Cologne. She then obtained a Cancer Aid professorship, and in 2012 became full professor with a joint appointment at the Department of Dermatology and the excellence cluster CECAD. Since 2015, she is the scientific coordinator of the DFG funded Collaborative Research Center 829 “Molecular mechanisms regulating Skin Homeostasis”, as well as from 2019 coordinates the excellence cluster CECAD on aging and aging-associated diseases. Carien Niessen is a member of the international scientific advisory board of DEBRA International, serves as a section editor of the Journal of Investigative Dermatology, and furthermore serves as an editor of Tissue barriers and the Journal of Cell Biology.
Intercellular adhesion and cell polarity are crucial determinants of tissue architecture and morphogenesis. How regulation of cell adhesion and cell shape contributes to the formation and life-long regeneration of the epidermal barrier is only poorly understood. The Niessen laboratory asks how regulation of cell and tissue architecture controls the formation, maintenance and regeneration of the self-renewing, multi-layered skin epidermis. Using a combination of mouse genetics, high resolution imaging, proteomics and biophysical approaches we address at different scale lengths how cadherin adhesive mechanical signals, polarity complexes and tyrosine receptor kinase activity (a) coordinate cell positioning with cell fate, (b) the positioning and generation of the tight junctional and stratum corneum barrier, and (c) integrate cell architecture and signaling to coordinate tissue organization.
Key recent publications
Guenschmann, C, Stachelscheid H, Akyüz MD, Schmitz A, Missero, C#, Bruning, JC# and Niessen CM# (2013) IGF-1 controls epidermal morphogenesis via regulation of FoxO-mediated p63 inhibition. Developmental Cell, 26: 176-87
Niessen MT, Scott, J, Zielinski, J, Vorhagen S, Blanpain, C, Leitges, M. and Niessen CM (2103) The cell polarity protein aPKC couples asymmetric divisions to cell fate decisions in the epidermal lineage. J. Cell Biol, 202:887-900
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, 135:1501-9
Rübsam M*, Broussard JA*, Wickström SA, Nekrasova O, Green KJ and Niessen CM. (2017) Adherens junctions and Desmosomes coordinate Mechanics and Signaling to orchestrate Tissue morphogenesis and Function: An evolutionary Perspective. Cold Spring Harb Perspect Biol, pii: a029207
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. Nature Communications, 8:1250
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. Nat Cell Biol, 20:69-80.
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: 5136-46
Quang Le H, Ghatak, S., Yeung, C-Y.C., Tellkamp, F., Gunschmann, C., Dieterich, C., Yeroslaviz, A., Habermann, B., Pombo, A., Niessen, CM and Wickström, S. (2016) Mechanical regulation of transcription drives Polycomb mediated gene silence during lineage committment. Nat Cell Biol 18: 864-875
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
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, pii: e37629.
Persa OD, Niessen CM. (2019) Epithelial polarity limits EMT. Nat Cell Biol. 21:299-300
Peters F*, Tellkamp F*, Brodesser S, Wachmuth E, Tosetti B, Karow U, Bloch W, Utermohlen O, Kronke M, Niessen CM Murine epidermal Ceramide Synthase 4 is a key regulator of skin barrier homeostasis. J. Invest. Derm. Accepted
# shared last and corresponding author