Redox & Metabolism

Redox signaling and metabolism

Redox chemical reactions have been identified for broad uses in and between cells to generate and relay signals. Research in this field is greatly hindered by the lack of available methods to detect redox-signaling molecules and protein redox states in cells and cell subdomains. One focus of our research is to engineer fluorescent protein-based redox biosensors.

Fan Y, Makar M, Wang MX, Ai HW*. Monitoring thioredoxin redox with a genetically encoded red fluorescent biosensor. Nat Chem Biol. 2017 Sep;13(9):1045-1052. PMID: 28671680; PMCID: PMC5605834.

Youssef S, Ren W, Ai HW*. A Genetically Encoded FRET Sensor for Hypoxia and Prolyl Hydroxylases. ACS Chem Biol. 2016 Sep 16;11(9):2492-8. PMID: 27385075; PMCID: PMC5026574.

Pang Y, Zhang H, Ai HW*, Genetically Encoded Fluorescent Redox Indicators for Unveiling Redox Signaling and Oxidative Toxicity, Chemical Research in Toxicology 34 (8), 1826-1845, 2021

Our lab expanded the strategies for creating fluorescent redox probes, by introducing noncanonical amino acid (ncAAs) using a genetic code expansion technology into circularly permuted fluorescent proteins to derive novel biosensors.

Chen ZJ, Tian Z, Kallio K, Oleson AL, Ji A, Borchardt D, Jiang DE, Remington SJ, Ai HW*. The N-B Interaction through a Water Bridge: Understanding the Chemoselectivity of a Fluorescent Protein Based Probe for Peroxynitrite. J Am Chem Soc. 2016 Apr 13;138(14):4900-7. PMID: 27019313; PMCID: PMC4958459.

Chen ZJ, Ren W, Wright QE, Ai HW*. Genetically encoded fluorescent probe for the selective detection of peroxynitrite. J Am Chem Soc. 2013 Oct 9;135(40):14940-3. PMID: 24059533.

Chen S, Chen ZJ, Ren W, Ai HW*. Reaction-based genetically encoded fluorescent hydrogen sulfide sensors. J Am Chem Soc. 2012 Jun 13;134(23):9589-92. PMID: 22642566.

Chen ZJ, Zhang S, Li X, Ai HW*. A high-performance genetically encoded fluorescent biosensor for imaging physiological peroxynitrite. Cell Chem Biol. 2021 Jan 27; S2451-9456(21)00013-1. PMID: 33581056.

Nucleotide sugars are used by glycosyltransferases to synthesize glycoproteins, glycosaminoglycans, glycolipids, and glycoRNA. UDP-GlcNAc also serves as the donor substrate for forming O-GlcNAc, a dynamic intracellular protein modification involved in diverse signaling and disease processes. Nucleotide sugars are thus important cell metabolites connecting nutrition, metabolism, signaling, and disease.

Li Z, Zhang J, Ai HW*. Genetically Encoded Green Fluorescent Biosensors for Monitoring UDP-GlcNAc in Live Cells, ACS Central Science 2021, 2021 Oct 27;7(10):1763-1770. PMID: 34729420; PMCID: PMC8554846