Welcome to the Cilia Group
We study the primary cilium, a surface-exposed sensory organelle that coordinates cellular signaling during development and in tissue homeostasis, and when defective results in numerous diseases and pleiotropic syndromes called ciliopathies that affect most tissues and organs in our body. 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 primary cilia assemble, disassemble, and function to coordinate cellular signaling networks during embryonic development and in tissue homeostasis.
Our laboratories are equipped for:
- culturing of mouse and human cell lines and primary cell cultures, including stem cells, epithelial cells and fibroblasts
- molecular biological methods including
1) PCR, cloning procedures and plasmid construction,
2) transient and stable expression of tagged wild type and mutated proteins,
3) knockdown and knockout strategies in cell cultures,
4) Immunoprecipitation and size exclusion chromatography,
5) SDS-PAGE and quantitative western blotting,
6) quantitative real-time PCR - fluorescence optical methods: epifluorescence (Olympus BX63) and spinning disc confocal microscopy (Olympus IX83) systems for fixed samples (cell cultures and tissues) and live cell imaging
- collaborative work on zebrafish and proteomics
Our research proceeds via several tracks to understand how primary cilia organize spatiotemporal signaling networks and in what way perturbation of these networks contribute to health and disease. One direction focuses on characterization of novel ciliary disease genes, and how mutations in these genes lead to congenital heart and brain disorders. A second track is aimed at understanding vesicular trafficking to and from primary cilia, and how defects in these processes are linked to cancer, developmental syndromes and neurodegenerative disorders. Previously, we uncovered a series of new trafficking pathways and molecules that modulate the ability of primary cilia to respond to specific growth factors and morphogens in PDGFRα, TGFβ/BMP and Hedgehog signaling and to adjust the signaling output of receptor activation. These results provide important molecular insight into the etiology of ciliopathies and identify new disease genes linked to ciliary functions.
Gonçalves, AB, Joensen, BB, Hasselbalch, SK, Martens, P, Ohlsen, SK, Quinodoz, M, Nikopoulos, K, Jeppesen, MPD, Weiss, C, Christensen, ST, Patzke, S, Rivolta, C, Andersen, JS, Farinelli, P, Pedersen, LB (2020) CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels. BioRxiv
Farooq, M, Lindbæk, L, Krogh, N, Doganli, C, Keller, K, Mönnich, M, Gonçalves, AB, Sakthivel, S, Mang, Y, Fatima, A, Andersen, VS, Hussain, MS, Eiberg, H, Hansen, L, Kjaer, KW, Gopalakrishnan, J, Pedersen, LB, Møllgård, K, Nielsen, H, Baig, SH, Tommerup, N, Christensen, ST, Larsen, LA (2020) RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis. Nature Communications 11, 5816. https://doi.org/10.1038/s41467-020-19658-0
Anvarian, Z, Mykytyn, K, Mukhopadhyay, S, Pedersen, LB and Christensen, ST (2019) Cellular signalling by primary cilia in development, organ function and disease. Nature Reviews Nephrology 15, 199-219.
Mönnich, M, Borgeskov, L, Breslin, L, Jakobsen, L, Rogowski, M, Doganli, C, Schrøder, JM, Mogensen, JB, Blinkenkjær, L, Harder, LM, Lundberg, E, Geimer, S, Christensen, ST, Andersen, JS, Larsen, LA and Pedersen, LB (2018) CEP128 localizes to the subdistal appendages of the mother centriole and regulates TGF-β/BMP signaling at the primary cilium. Cell Reports, 22, 2584-2592.
Schmid, FM, Schou, KB, Vilhelm, MJ, Holm, MS, Breslin, L, Farinelli, P, Larsen, LA, Andersen, JS, Pedersen, LB and Christensen, ST (2018) IFT20 promotes feedback inhibition of ciliary PDGFRα signaling by regulating stability of Cbl E3 ubiquitin ligases. Journal of Cell Biology 217, 151-161.
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.
The Cilia Group participated in 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 organized the EMBO Workshop Cilia 2018 in Copenhagen, October 2-5, 2018 (http://meetings.embo.org/event/18-cilia)
Marie Curie Innovative Training Network (ITN)
https://www.scils.eu/
UCPH Programme for Interdisciplinary Research on Ciliopathies
www.globalgenes.ku.dk/
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The primary cilium (Video) (2017) https://www1.bio.ku.dk/nyheder/nyheder/the-primary-cilium/ |
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Rugekasse for fremtidens talenter (2016) http://publikationer.lif.dk/Magasin/med01/ (Pages 20-23) |
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Primære cilier - cellernes ultimative antenner (Video) (2015) |
Coordination of Master courses (Prof. Søren Tvorup Christensen)
Advanced Cell Biology
Cellular Signalling in Health and Disease
Coordination of Bachelor courses (Prof. Lotte Bang Pedersen)
Cellebiologi for biokemikere
Master and Bachelor projects
See under projects and Department of Biology Project database
Members
| Name | Title | Job responsibilities | Phone | |
|---|---|---|---|---|
| Csenge Kata Rezi | PhD Fellow | |||
| Lotte Bang Pedersen | Professor | +4529803551 | ||
| Maria Schrøder Holm | Laboratory Technician | +4535330176 | ||
| Søren L. Johansen | Laboratory Technician | +4535330258 | ||
| Søren Tvorup Christensen | Professor | +4535330255 |
Contact
The Cilia Group
Cell Biology and Physiology
Universitetsparken 13
DK-2100 Copenhagen Ø, Denmark
Professor Lotte Bang Pedersen
Email: lbpedersen@bio.ku.dk
Professor Søren Tvorup Christensen
Email: stchristensen@bio.ku.dk