Hui Sun Laboratory

Many highly impactful medicines target membrane receptors (e.g., weight loss drug Ozempic and cancer drug anti-PD1). The Sun lab has devoted its efforts to the discovery, mechanistic study and identification of chemical modulators of novel membrane receptors that play important roles in physiology and diseases. The first endeavor is to elucidate the receptor mechanism that mediates cellular uptake of vitamin A, a multitasking chemical that is essential for human vision and human survival. We discovered this elusive membrane receptor using a novel technique and developed novel real-time monitoring techniques to study its molecular mechanism. We further identified potent small molecule modulators can potentially be used in treating human diseases caused by insufficient or excessive retinoid level (relevant disease areas include ophthalmology, dermatology, and oncology).

The second endeavor is to elucidate the molecular mechanism and to identify novel chemical agonists for a new type of membrane receptors highly enriched in pathogenic blood vessels. After several years of unbiased and large-scale screening, we identified the receptors of the most potent endogenous anti-angiogenic factor. These are the only proteins in the human genome that are known to confer cell-surface binding to the factor and to transduce its signal into the cells. Their highly specific expression in pathogenic blood vessels in vision diseases and tumors matches the therapeutic targets of the endogenous factor. By developing a novel fluorescence-based technique, we identified potent chemical compounds that target this receptor to specifically kill pathogenic blood vessels in vision disease and also tumor blood vessels to lead to effective tumor killing in vivo. In addition, we also developed a novel technique to screen for receptor-activating antibodies and successfully identified antibody drug candidates after large-scale screening 10 billion antibody clones. They are candidate drugs that can be used to treat a wide range of human diseases driven by pathogenic angiogenesis including major blinding diseases and diverse types of cancer.