We use state-of-the-art tools to build small organic molecules and study their functions in biological systems. Our lab started in 2004, focusing on addressing standing issues in natural product synthesis, and has expanded since to include using chemical biology approaches to improve our understanding of protein functions.

In early years, we exploited single-electron transfer chemistry and photochemistry to construct strategic C-C bonds of the target molecules in synthesis. This effort accumulated to the completion of the synthesis of nakiterpiosin, dibromophakellstatin, sceptrin, ageliferin, massadine and axinellamine. We also developed new transition metal-catalyzed and photochemical reactions to enable C-C and C-X bond formations in challenging settings. Our current focus is the design and synthesis of functional molecules.
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Our interest in the Wnt signaling pathway started in 2005 when Lawrence Lum (Department of Cell Biology) demonstrated for the first time that the Wnt pathway is druggable (Feng Cong at Novartis made the same discovery concurrently). Our lab has since developed a series of small-molecule PORCN inhibitors that suppress the secretion of Wnt proteins and TNKS inhibitors that promote the degradation of β-catenin. Currently, we are using a combination of chemical and biological tools to study how TNKS controls Wnt/β-catenin signaling.
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Our lab also has a longstanding interest in drugging the cGAS-STING signaling pathway. We worked with James Zhijian Chen (Department of Molecular Biology) who discovered the long-sought cytosolic DNA sensor cGAS to determine the chemical structure of cGAMP in 2012. We have subsequently elucidated the molecular basis of its specific recognition by STING and developed an investigational drug for cancer based on cGAMP. We are now seeking innovative solutions to modulating cGAS/STING signaling to benefit cancer and autoimmune diseases patients.
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