Chemical Biology; Fluorescence and Bioluminescence Imaging; Protein Engineering

Our lab uses interdisciplinary approaches in biophysics, chemical biology, bioengineering, and electrophysiology to study and manipulate complex biological systems, with a focus on the development of novel molecular biosensors to peer into cells and organisms to understand communications. We use a collection of technologies, such as protein engineering, fluorescence imaging, bioluminescence imaging, synthetic chemistry, and electrophysiology to dissect biological pathways related to metabolism, redox signaling, and neurotransmission. Our immediate goal is to monitor biological signaling in real time with excellent spatial resolution and molecular precision in physiologically relevant environments. Our long-term goal is to apply these new probes to live cells and rodent models to understand communications relevant to diabetes, cognition and behavior, and neurological disorders. Moreover, our basic research efforts are actively being translated to develop novel protein-based diagnostics and therapeutics.

Recent publications:

H.W Yeh, and H-w. Ai*, “Development and Applications of Bioluminescent and Chemiluminescent Reporters and Biosensors”, Annu. Rev. Anal. Chem., 12: Doi: 10.1146/annurev- anchem-061318-115027.

H.W. Yeh, Y. Xiong, T. Wu, M. Chen, A. Ji, X. Li, and H-w. Ai*, “ATP-independent bioluminescent reporter variants to improve in vivo imaging”, ACS Chemical Biology, 2019, 14 (5): 959-965.

H.W. Yeh, O. Karmach, M. Martins-Green, and H-w. Ai*, “Red-shifted luciferase-luciferin pairs enhance bioluminescence in vitro and in vivo”, Nature Methods, 2017, 14: 971–974.

Y. Fan, and H-w. Ai*, “Monitoring thioredoxin redox with a genetically encoded red fluorescent biosensor”, Nat. Chem. Biol., 2017, 13: 1045-1052.

W. Ren, A. Ji, and H-w. Ai*, “Light Activation of Protein Splicing with a Photocaged Fast Intein”, J. Am. Chem. Soc., 2015, 137: 2155–2158.

A. Ji, W. Ren, and H-w. Ai*, “A Highly Efficient Oxidative Condensation Reaction for Selective Protein conjugation”, Chem. Commun., 2014, 50: 7469-7472

Z. Chen, W. Ren, Q.E. Wright and H-w. Ai*, “Genetically Encoded Fluorescent Probe for the Selective Detection of Peroxynitrite”, J. Am. Chem. Soc., 2013, 135: 14940-14943.