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Dr. Shi Liu's Lab
Pharmacology, Enzymology, and Beyond 

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Research

We are a chemical biology research group in the Department of Pharmacy and Pharmaceutical Sciences at the National University of Singapore. Our lab is broadly interested in mechanistic exploration and functional engineering of molecular interactions that are essential to physiological processes or important to synthetic biology applications. To help uncover fundamental insights for important biology questions, we integrate expertise from diverse disciplines, including but not limited to synthetic organic chemistry, molecular biology, cell biology, and computationally guided molecular design, to create molecular probes or biosensors with tailored activities. Guided by our mechanistic understanding, we are developing novel high-throughput assays for lead discovery and inventing robust synthetic platforms for lead optimization. These efforts are expected to enable new strategies in molecular pharmacology and ultimately lead to therapeutics with improved efficacy.

Latest Publications

GPCR Chemical Biology and Pharmacology

1. Liu, S.; Daley, E. J.; Tran, L. M. L.; Yu, Z.; Reyes, M.; Dean, T.; Khatri, A.; Levine, P. M.; Balana, A. T.; Pratt, M. R.; Juppner, H.; Gellman, S. H.; Gardella, T. J. Backbone Modification Provides a Long-Acting Inverse Agonist of Pathogenic, Constitutively Active PTH1R Variants. J. Am. Chem. Soc. 2024, 146, 6522-6529.

2. Liu, S.#; Yu, Z.#; Daley, E. J.; Bingman, C. A.; Bruchs, A. T.; Gardella, T. J.; Gellman, S. H. Altered Signaling at the PTH Receptor via Modified Agonist Contacts with the Extracellular Domain Provides a Path to Prolonged Agonism In Vivo. Proc. Natl. Acad. Sci. U.S.A. 2022, 119, e2212736119 (Direct Submission, #equal contribution)

3. Liu, S.; Jean-Alphonse, F. G.; White, A. D.; Wootten, D.; Sexton, P. M.; Gardella, T. J.; Vilardaga, J. P.; Gellman, S. H., Use of Backbone Modification to Enlarge the Spatiotemporal Diversity of Parathyroid Hormone Receptor-1 Signaling via Biased Agonism. J. Am. Chem. Soc. 2019, 141, 14486-14490. 

4. White, A. D.; Pena, K. A.; Clark, L. J.; Maria, C. S.; Liu, S.; Jean-Alphonse F. G.; Lee, J. Y.;Lei, S. F.; Cheng, Z; Tu, C. L.; Fang, F.; Szeto, N.; Gardella, T. J.; Xiao, K.; Gellman, S. H.; Bahar, I.; Sutkeviciute, I.; Chang, W; Vilardaga, J. P. Decoding location bias information of cAMP signaling in a class B GPCR. Sci. Signal. 2021, 14, eabc5944

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