Vladimir Katanaev Professeur associé
Vladimir Katanaev received his PhD in 2000 from the Institute of Biochemistry, University of Fribourg, working with Matthias Wymann on signal transduction in leukocyte chemotaxis. From 2000 to 2005 he worked as postdoctoral research fellow and subsequently as associate research scientist at the Department of Genetics and Development of Columbia University, New York, in the lab of Andrew Tomlinson. There he started his research on the Wnt/Frizzled signaling in Drosophila development. He continued to study this signaling cascade in Drosophila and mammalian cells as an independent group leader at the University of Konstanz, where he also completed his Habilitation in 2010. He joined the Department of Pharmacology and Toxicology in April 2011 as associate professor, relocating his laboratory from Konstanz to Lausanne.
Keywords: Wnt; Frizzled; signal transduction, G protein-coupled receptors, Drosophila
Domaine de recherche
Animal development is a tightly regulated process, orchestrated by several types of intracellular signaling pathways, including signaling by the Wnt family of lipoglycoproteins and their G protein-coupled Frizzled receptors. The Wnt/Frizzled pathway is mostly silent in the adult. However, both improper overactivation and underactivation of this pathway can lead to diseases. Insufficient Wnt pathway activity underlies defects in tissue regeneration and the decreased proliferative potential of various stem cells; it may also lead to certain neurodegenerative disorders. On the other hand, misactivation of this signaling, e.g. through overproduction of the Wnt ligands or mutational activation of the downstream components of the pathway, promotes carcinogenesis, especially in the colon and breast.
We study signal transduction in this developmentally and medically important pathway using a combination of approaches, such as Drosophila genetics, mammalian cell culture, protein biochemistry, and systems biology. We are particularly interested by the GPCR properties of Frizzled receptors, as well as identification and characterization of the signaling partners of the heterotrimeric Go protein - an immediate transducer of Frizzled receptors in flies and mammals. Having built a high-throughput in vitro assay monitoring Frizzled GPCR activation, we are also aiming at identification of small-molecule agonists and antagonists of human Frizzled proteins, which may become lead compounds for regenerative and anti-cancer treatments.
Left: Drosophila wing (pink) becomes aberrant and underdeveloped if Axin, the inhibitor of Wnt signaling, is overexpressed (green). This phenotype is partially rescued by co-expression of the heterotrimeric Go protein (yellow), confirming other physical and genetic interactions between Axin and Gαo (Egger-Adam and Katanaev, Dev. Dyn. 2010).
Right: Frizzled receptors, as well as the heterotrimeric Go protein, can both activate Rab5 and stimulate endocytosis, leading to formation of giant endosomes (arrows) in Drosophila hemocytes. Rab5 emerges as a general interaction partner of Gαo and amplifier of Wnt/Frizzled signaling (Purvanov, Koval, Katanaev, Sci. Signal. 2010).