Welcome to the Wang Lab

Modulate RNA processes and immune responses

Drug discovery | Medicinal Chemistry | Chemical biology

 

Research

Modulation of RNA splicing by small molecules

The human genome contains ~30,000 genes but only <14% were conventionally considered “druggable”. The major reasons for the low ratio include lack of proper small molecule binding site or low selectivity. However, the definition of druggable and undruggable genes is based on an assumption that a reasonable design of small molecule drug is through the specific interaction between the small molecule and the gene encoding protein. Targeting nucleic acids, one or two steps back in the central dogma, can potentially solve the undruggable problem but historically suffered from critics of lack of selectivity.
In recent years, RNA-targeting small molecules have been developed and optimized to overcome the specificity problem. Especially, two RNA-binding small molecule splicing regulators, RG-7916 and LMI-070, has been evaluated in clinical trials for the treatment of spinal muscular atrophy and demonstrated promising results. Our group is focused on this new pharmacological modality and aims at the discovery of splice site-specific RNA-targeting small molecules as biological probes or medicine.

Exploring new methods to regulate innate immune response in mammalian cells

In the recent years, immuno-oncology has become a major direction for anti-cancer research, including the development of PD-1/PD-L1 monoclonal antibodies as checkpoint inhibitors. However, concerns have been raised regarding the low response rates (20-30%) for these therapies in solid tumor treatment, including blockbuster drugs Keytruda and Opdivo. One of the major reasons for the low response is the lack of activated T cell in the tumor microenvironment. Since the 1960’s, myriads of immune response agonists have been used to treat cancer, including BCG vaccines, IL-2 and TLR agonists, etc. Due to complexity of the innate immune response and the lack of true understanding of the mechanism of action, none of these methods can activate T cells in a safe, potent but controllable manner across larger numbers of patients.
Our group is interested in exploring innate immune response pathways in a chemical biology approach and uncovering new biological mechanisms and chemical space as immunotherapies.

 

Group News

07/21/2020

The group is awarded by BioNexus KC for the treatment of spinal muscular atrophy! Click "Read More" for the press release.

 

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