Welcome to the Cilia Group
Primary cilia are surface-exposed sensory organelles that regulate a vast number of cellular signaling pathways to control the development and function of multiple tissues and organs. Ciliary defects therefore result in numerous diseases and pleiotropic syndromes called ciliopathies. We employ a variety of different approaches, from biochemistry, molecular biology and proteomics to mammalian cell cultures and zebrafish models, to study the molecular mechanisms by which cilia assemble, disassemble, and function to coordinate cellular signaling networks during development and tissue homeostasis. These studies include the mechanisms by which the balanced activation of ciliary signaling is regulated by microtubule-dependent vesicular trafficking to and from cilia, and how defects in these processes are linked to cancer and developmental disorders, including congenital heart and brain diseases. Recently, we uncovered a series of new pathways and molecules that modulate the ability of primary cilia to respond to specific growth factors and morphogens in Hedgehog, PDGFRα and TGFβ/BMP signaling and to adjust the signaling output of receptor activation. These results provide important molecular insight into the etiology of ciliopathies and identify new candidate disease genes.
The Cilia Group is part of the UCPH Excellence Program for Interdisciplinary Research: Global genes, local concerns: Legal, ethical and scientific challenges in cross-national biobanking exploitation ( http://globalgenes.ku.dk/).
The Cilia Group is a member of the Nordic Cilia and Centrosome Network (www.nordiccilia.org) and organizes the upcoming EMBO Workshop Cilia 2018 in Copenhagen, October 2-5, 2018 (http://meetings.embo.org/event/18-cilia)
Schmid, FM, Schou, KB, Vilhelm, MJ, Holm, MS, Breslin, L, Farinelli, P, Larsen, LA, Andersen, JS, Pedersen, LB and Christensen, ST. IFT20 promotes feedback inhibition of ciliary PDGFRα signaling by regulating stability of Cbl E3 ubiquitin ligases. Journal of Cell Biology (In press).
Schou, KB, Mogensen, JB, Nielsen, BS, Morthorst, SK, Aleliunaite, A, Serra-Marques, AMA, Saunier, S, Bizet, A, Veland, IR, Akhmanova, A, Christensen, ST & Pedersen, LB (2017). KIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signaling. Nature Communications 8, 14177
Christensen, ST, Morthorst, SK, Mogensen, JB & Pedersen, LB (2017) Primary cilia and coordination of receptor tyrosine kinase (RTK) and transforming growth factor β (TGF-β) signaling. Cold Spring Harbor Perspectives in Biology 9(6), a028167
Pedersen, LB, Mogensen, JB & and Christensen, ST (2016) Endocytic Control of Cellular Signaling at the Primary Cilium. Trends in Biochemical Sciences 41, 784-797.
Schou, KB, Pedersen, LB & Christensen, ST (2015) Ins and outs of GPCR signaling in primary cilia. EMBO Reports 16(9), 1099-1113.
Nielsen, BS, Malinda, RR, Schmid, FM, Pedersen, SHF, Christensen, ST & Pedersen, LB (2015) PDGFRβ and oncogenic mutant PDGFRα D842V promote disassembly of primary cilia through a PLCγ- and AURKA-dependent mechanism. Journal of Cell Science 128, 3543-3549.
Clement, CA , Ajbro, KD , Koefoed, K, Vestergaard, ML , Veland, IR , Henriques de Jesus, MPR , Pedersen, LB, Benmerah, A , Andersen, CY , Larsen, LA & Christensen, ST (2013) TGF-β Signaling Is Associated with Endocytosis at the Pocket Region of the Primary Cilium. Cell Reports 3 (6), 1806-1814.
Veland, IR , Montjean, R, Eley, L , Pedersen, LB , Schwab, A, Goodship, J , Kristiansen, K , Pedersen, SHF , Saunier, S & Christensen, ST (2013) Inversin/Nephrocystin-2 is required for fibroblast polarity and directional cell migration. PLoS One 8 (4).
Clement, DL, Mally, S, Stock, C, Lethan, M, Satir, P, Schwab, A, Pedersen, SF & Christensen, ST (2013) PDGFRα signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways. Journal of Cell Science 126 (4): 953-965.
Schrøder, JM , Larsen, J , Komarova, Y, Akhmanova, A , Thorsteinsson, RI , Grigoriev, I, Manguso, R , Christensen, ST , Pedersen, SHF , Geimer, S & Pedersen, LB (2011) EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms. Journal of Cell Science 124, 2539-2551.
Schneider, L, Cammer, M, Lehman, J, Nielsen, SK, Guerra, CF, Veland, IR, Stock, C, Hoffmann, EK, Yoder, BK, Schwab, A, Satir, P & Christensen, ST (2010) Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cell Physiol Biochem, 25, 279-292.
Technicians and scientific assistants
Søren Lek Johansen
Marie Schrøder Holm
Martin Juel Vilhelm
Post docs and students
Dr. Pietro Farinelli
Dr. Zeinab Anvarian
Dr. Loretta Breslin
Stine Kjær Morthorst
Patricia Cherie Sharku
Gustav Peder Mohr Olsen
Christian Ilsøe Svendsgaard