Søren Tvorup Christensen
Cell Biology and Physiology, University of Copenhagen
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.