Our group focuses on areas of organic chemistry and chemical biology in order to provide useful small molecules and tools to facilitate researches in life sciences. For every biologically active small molecule, there are two basic scientific questions we are trying to address. Focus 1: why is the molecule biologically active (mechanism-of-action) and what is the structure-activity relationship? Focus 2: based on our understanding of the first aspect, how could we design and prepare small molecules that better suit our needs? By taking full advantage of the state-of-the-art synthetic organic chemistry and chemical biology technologies, we are working on a wide range of projects, including:

1. Anti-cancer compounds of clinical value with identified mechanism of action; potent cytotoxic natural products with high selectivity against genetically defined cancer cells

2. Promising antimicrobial natural products without elucidated mechanism of action; clinically used antibiotics

3. Small-molecule modulators of various ion channels pertaining to the neurological system; neurotrophic natural products

4. Compounds regulating cell fate with potential application in regenerative medicine, such as in the area of differentiation and reprogramming, especially the generation of chemically induced pluripotent stem cells

5. Pheromones and quorum sensing molecules important for intra- or inter-species chemical communication; hormones and primary metabolites important for delivering signals between different organs and tissues

De novo syntheses of complex small molecules, especially natural products, not only provide sufficient quantities of compounds that suffer from problems of purification or abundance, but also endow us the unique ability to accurately modify the targeted chemotypes. Factors of efficiency, modularity, robustness and scalability are considered and balanced in our synthetic routes, which, if successful, would enable efficient preparation of the targeted small-molecule library and exploration of the associated chemical biology. We are keen on developing novel cascade chemistry by harnessing the reactive intermediates, which often involve the rearrangement of molecular skeletons.

We are also particularly interested in organic reactions that could take place in live cells. The in vivo chemistry could be implemented in developing small-molecule probes that is turned “on” or “off“ by certain means, such as light of a particular wavelength. These activatable small-molecule probes would allow us to precisely manipulate biological system with exceptional temporal and spatial resolution. On the other hand, we work on the design and syntheses of compounds that specifically react with the endogenous amino acid residues under physiological conditions to interrogate the protein of interest from a new angle.

Tailored according to the specific needs in different biology fields, our projects focus upon the investigation and utilization of the interaction of small molecules and biomolecules, in which the innovations in chemistry would play a vital role.