Research Group Molecular Embryology

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Research

Overview

How cells communicate with their environment via cell-cell interactions and by growth factors is a key question in the molecular life sciences, including tumor biology. Among them, Wnt signaling plays an important role in embryonic development and cancer. Our work on Wnt signaling investigates the biochemical mechanism and physiological role of signal transduction by Wnt glycoproteins in mediating cell growth and differentiation, processes essential for embryonic development and cancer progression. We also study R-spondins, a family of secreted proteins that play a critical role in the regulation of the Wnt signaling pathway, which is involved in various developmental processes and in cancer. Additionally, our research explores the interactions between DEAD box RNA helicases (DDX proteins) and protein kinases, revealing their potential to stimulate kinase activity, which has broad implications in RNA biology and signal transduction. Furthermore, we have introduced ROTACs, bispecific WNT- and BMP-signaling-disabled R-spondin chimeras, which leverage the specificity of these stem cell growth factors for targeted protein degradation, offering new insights and therapeutic approaches for cancer. Our comprehensive research efforts enhance the understanding of the molecular mechanisms underlying cell differentiation, tissue homeostasis, and tumorigenesis.

We currently pursue four main lines of research. (1) We described that all cilia classes (flagella, primary cilia, multi-cilia) are Wnt-signaling organelles and we currently investigate the physiological importance of this signaling in mouse physiology. (2) We showed that DEAD box RNA helicases (DDX proteins) are a new class of regulators of protein kinases. We investigate the mechanism of action, notably in protein condensates during Wnt signaling and the biological role of the DDX-kinase interactions. (3) We study the role and biochemical mechanism of action of R-spondins, a class of Wnt agonist that play an important role in development as well as oncogenes and tumor suppressors. (4) We develop ROTACs as a novel class of protein targeting chimeras in cancer therapy.

We are part of � and funded by the CRC 1324: Mechanisms and functions of Wnt signaling�