Main Fields of Research, Abstract
The development of multicellular organisms is governed by cell-cell communication and it is a surprisingly small set of conserved signaling cascades that mediate this communication. These regulators of animal development, which are conserved from Cnidarians to mammals, include the Wnt, Hedgehog, TGFβ/BMP, and Hippo pathways. Our goal is to understand how these signaling proteins control growth and patterning during animal development. The insights gained will help us to understand and intervene in situations of miscommunication that lead to diseases, such as cancer.
One focus is the Wnt pathway. Here we are examining various aspects of the processes underpinning this cascade: from the control of the secretion of the Wnt proteins themselves to the genetic program activated in the responding cells. The key to understanding the elicited genetic program is to figure out how the two key nuclear effectors - β-catenin and TCF - act. We have developed animal models (both mouse and Drosophila) that enable, for the first time, the dissection of the signaling and structural functions of β-catenin in vivo. In a related subproject we are using these and other tools to explore the connection between Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT), cancer “stemness”, and metastasis. In particular, we are delineating the contribution of the nuclear co-factors of β-catenin - Bcl9, Bcl9L and Pygopus - to the transcriptional reprogramming occurring during tumorigenesis and metastasis.
A second relevant focus is our use of Drosophila to study growth control. As an example, we have recently developed a Drosophila tumor model that we can use to identify genes, which are specifically required for tumor growth. With this model we can use the power and speed of Drosophila genetics to reveal weak points of tumor progression We found that reduction of phosphoinositide 3-kinase (PI3K) activity resulted in very small tumors while only slightly affecting growth of wild-type tissue. Hence showing that the tumor cells have become dependent on PI3K function and that reduction of PI3K activity synthetically interferes with tumor growth. Our ongoing work is helping to elucidate the intricate mechanisms underlying tumorigenesis.
Main Fields of Research, Keywords
In vivo animal models (mouse, Drosophila melanogaster), Drosophila melanogaster, colon cancer, breast cancer, signal transduction, developmental biology, Wnt signaling, β-catenin
Special Techniques and Equipment
Unique animal models for Wnt pathway analysis (mouse and Drosophila), Drosophila genetics, systems biology level analysis of pathway activity: proteomics, transcriptomics
Education and Training
We have opportunities for Master’s students, PhD students, and postdoctoral fellows. The Institute hosts regular seminars with international speakers. We also hold regular journal clubs, data clubs and group meetings.