Our research focuses on two main themes: detailed understanding of Wnt/β-catenin signaling via discovery of new pathway modulators and exploring the role of Wnt/β-catenin signaling in regeneration of the adult central nervous system by using zebrafish as model.
On one side, our lab is interested in understanding how Wnt/β-catenin signaling pathway activity is finetuned i.e. regulated by a variety of positive and negative modulators. Here we have two main lines of research. First, we aim at understanding the role of membrane rafts, which are the specialized cell surface nanodomains known to have critical functions in regulation of various signaling pathways, in Wnt-receptor complex activation. This is an interdisciplinary study that combines molecular and cellular biology techniques with advanced biophysical methods. Disclosure of the functional role of membrane raft nanodomains in Wnt signal transduction in a broader manner will shed light on the drug discovery studies targeting the pathway proteins preferring rafts.
Second, by exploiting the feedback regulation feature of the Wnt/β-catenin pathway, we aim to characterize novel Wnt targets that might act as pathway modifiers. To identify Wnt target genes, we will apply an RNAsequencing based whole transcriptome analysis and analyze genes that are differentially expressed upon pathway manipulation. Characterization of universally regulated Wnt targets might aid in discovery of novel Wnt pathway modifiers. Drug candidates that will be discovered via screening of small molecules targeting these modifiers will create a perfect option for targeted treatment of cancer and minimize the side effects that might emerge during treatment. Here we may exploit zebrafish embryos to identify small molecules and further validate them in adult fish.
On the other side, we aim to understand the features of Wnt-responsive cells in the highly regenerative zebrafish brain in response to injury. As zebrafish can constitutively produce new neurons throughout their life at numerous zones of stem/progenitor cells all over the brain, it represents the most widespread vertebrate neurogenesis capacity known to date and thus constitutes an ideal platform to study brain regeneration. Here we will utilize an array of molecular and cellular biology techniques including micromanipulation, histological analyses and imaging. The outcome will help us understand how brain regeneration is controlled at the molecular level and why regeneration is very limited in the mammalian brain. Furthermore, by revealing the relationship of Wnt signaling to brain regeneration, this study will pave the way for improving brain regeneration and new approaches for treatment of neurodegenerative diseases or brain injury.