Protein Engineering: Advancing Imaging, Therapeutics, and Diagnostics

The Ai lab specializes in protein engineering and employs interdisciplinary approaches, including biophysics, bioanalytical chemistry, chemical biology, synthetic biology, and optical imaging. One of our main areas of focus is the development of molecular biosensors that provide insights into cellular and organismal signaling. We employ state-of-the-art techniques such as directed evolution, fluorescence imaging, bioluminescence imaging, synthetic chemistry, genetic screening, and mass spectrometry to unravel complex biological pathways related to redox biology, metabolism, and neuronal activity. Furthermore, we explore the application of protein-based tools in live cells and rodent models to better understand pathophysiology and develop innovative therapies for conditions like diabetes, Alzheimer’s disease, and cancer. As an emerging direction, we are also working on the development of biosensors that can serve as self-wellness alert devices or diagnostics in resource-limited settings.

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.