Dissecting the molecular basis of ciliopathies

Cilia are hair-like structures present on most vertebrate cell types. They are sensory hubs with a profound influence on cell proliferation, polarity and differentiation. Defects in cilia formation or function cause a range of developmental disorders categorized as ciliopathies.

The ciliopathies are multisystem disorders involving all major organs including kidney, brain, eye, airways and limbs, thus emphasizing the important roles that the cilium has in the function of most tissues. Mutations in > 150 genes have been identified as the molecular cause for human ciliopathies, however, the majority of ciliopathy patients remain genetically unexplained.

In our project we study a cohort of ciliopathy patients in which no clinically significant findings were detected on an analysis of a diagnostic panel of genes known to cause ciliopathies when mutated. Putative novel disease genes identified are screened in a ciliopathy patient cohort within our network of international collaborators. We further perform in vitro experiments and study animal models to reveal the effects of the novel mutations on cilia structure and function, and on downstream signal transduction pathways.

National collaborators
Prof. Strømme (Department of Pediatrics, OUS) and Prof. B. Paus, Dr. I-L Mero and Dr. Y. Sejersted (AMG): patient recruitment and clinical investigations.
Dr. S. Patzke (OUS, Radiumhospitalet): in vitro work.
Prof. H. Nilsen (UiO and Ahus): in vitro work.
Prof. C.V. Esguerra (NCMM, UiO): in vivo work. 

International collaborators:
Profs. N. Katsanis and E.E. Davis (Advanced Center for Translational and Genetic Medicine, Children’s Hospital of Chicago, USA): in vivo work and patient cohort.
Prof. C. Bergmann (University of Freiburg, DE): in vivo work and patient cohort.
Profs. B. Isidor and S. Küry (Centre Hospitalier Universitaire de Nantes, France): in vivo work and patient cohort.
Prof. V. Belengeanu (Victor Babes University of Medicine and Pharmacy of Timisoara, Romania): patient cohort. 

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