Assistant Professor, BIO5 Institute
Assistant Professor, Medicinal Chemistry-Pharmacology & Toxicology
The Wang laboratory is interested in developing novel chemical tools, including small molecules and miniproteins, to help better us understand biology, and in turn use that knowledge to design better drugs to fulfill unmet medical needs. The Wang laboratory consolidates expertise ranging from organic synthesis, peptide chemistry, rational drug design, molecular biology, electrophysiology, virology, to cell imaging, all in the same laboratory. This multi-disciplinary environment enables researchers in the Wang laboratory to explore various aspects of lead discovery. We are engaged in both rational drug design and high-throughput screening to discover the first-in-class chemical probes/drug candidates. As a practical application, we are interested in designing broad-spectrum antivirals targeting influenza viruses, especially multi-drug-resistant influenza viruses. Currently, we are exploring both viral proteins and host factors as antiviral drug targets. As an example, we have designed the first-in-class M2-S31N inhibitors, and these compounds have shown potent antiviral activity against multiple human influenza A strains, including the ones that are resistant to oseltamivir. In another example, we have identified several hits from a high-throughput screening campaign, and they have shown broad-spectrum antiviral activity against both influenza A and B strains with mechanisms distinct from that of known antiviral drugs. We believe that these novel hits will not only lead us to discover novel viral replication signaling pathways and open new opportunities for antiviral drug design, but also help us better understand the mechanism of drug resistance. In terms of combating antiviral drug resistance, we have no bias towards direct-acting antivirals versus host-targeting antivirals. We believe each class of antivirals has certain advantages and the ultimate solution to drug resistance might be combination therapy. We are also interested in designing inhibitors targeting ion channels and use them as tools to understand their structures, functions, and dynamics. Towards this goal, we are developing novel functional assays suitable for high-throughput screening of ion channel blockers. As an example, we have developed the yeast-growth restoration assay and have identified several novel chemotypes for the M2 proton channel from a high-throughput screening. We are now adapting this assay for the BM2 proton channel. In parallel, we are also designing channel blockers using computational methods, such as molecular dynamics simulation and molecular docking. Other targets of interest include voltage-gated proton channel, acid-sensing ion channel, and chloride ion channel.