What we do?
Our research interests are in chemical biology and RNA biochemistry. Our goal is to focus on the modulation of disease-related RNAs and to develop novel synthetic molecules that can modulate cellular signaling pathways. To this end, we take a multidisciplinary approach including synthetic organic chemistry, combinatorial chemistry, biochemistry and molecular biology. The discovered modulators will be potential therapeutics as well as chemical probes.
How to modulate RNAs?
We aim to discover novel chemical entities that modulate the function of disease-related RNAs. Our strategy includes i) direct inhibition of RNA structured site, ii) RNA degradation, and iii) RNA modulation with RNA modulating protein.
1) Direct inhibition
We will make compound libraries with various characteristic molecules including small molecules, peptidic molecules, and oligonucleotide-based molecules. Chemical structure of library will be taken from natural architecture in RNA structured site.
2) RNA degradation
We will use hetero-bifunctional molecules which are connected to Rnase recruiter and disease-related RNA binder with linkers. The chimeric molecule induces target RNA degradation by recruiting Rnase in close proximity. This approach has been used for degrading disease-related RNAs or undruggable protein mRNAs by utilizing Rnase L. We will use this "ribonuclease targeting chimera (RiboTAC)" strategy and further develop another class of RiboTAC. We aim to degrade RNA targets of broad range of diseases and messenger RNAs of undruggable proteins.
3) RNA modulation with epitranscriptome
RNA undergoes similar modification to DNA. These RNA base modifications, which are called “epitranscriptome”, play a pivotal role in biological processes such as pre-mRNA splicing, RNA degradation, RNA export, and mRNA translation. We will target the epitranscriptome processes to modulate RNA processing with compound libraries. We aim to destabilize unwanted RNAs and stabilize wanted RNAs.