Science in the Aye Lab
The Aye lab focuses on chemistry-driven methods development in Chemical Biology, with the goals to understand biochemistry and cellular biology of electrophile signaling pathways and molecular regulation of redox-sensitive and electrophile-responsive proteins of importance in human pathophysiology. In a parallel program distinct from redox regulation, the Aye lab studies proteins and pathways involved in mammalian genome maintenance, including the mechanisms of anticancer agents in clinical use that tap into DNA biogenesis.
Our Research Arena
- Synthetic Methodology
- Chemical Biology
- Molecular and Cell Biology
- and more recently, C. elegans and zebrafish in vivo research models
1) T-REX On-Demand Redox Targeting
We are exploiting T-REX, the target-specific redox perturbation platform that our lab has recently developed, to deconstruct individual oxidative and electrophilic signaling events in living systems, specifically, cultured mammalian cells, zebrafish, and C. elegans.
Fang & Fu et al., J Am Chem Soc (2013) 135 14496
Parvez & Fu et al., J Am Chem Soc (2015) 137 10
Lin et al., J Am Chem Soc (2015) 137 6232
Long et al., J Am Chem Soc (2016) 138 3610 – Selected by the JACS Editors as a JACS SpotsLight Article
Parvez & Long et al., Nature Protocols (2016) 11 2328
Long et al. ACS CRT (2016) (in honor of ACS CRT Young Investigator Award) – Selected as an ACS Editors’ Choice Article; Selected for Journal Cover Art
Long & Parvez et al. Nature Chemical Biology (2017) 13 333
[News & Views in the same journal (2017) Nature Chemical Biology 13 244]
Long et al. ACS Chemical Biology (2017) 12 586
Long et al. Cell Chemical Biology (2017) (Perspective) Just Accepted
Long & Lin et al. (2017) Revised and Resubmitted (original research)
Zhao et al. (2017) Under Peer Review (original research)
Long et al. (2017) In Revision (original research)
2) Novel Functions of Protein Multimers in Nucleotide Signaling, DNA regulation, and Genome Maintenance
We are seeking to advance mechanistic understanding of nucleotide drugs-driven protein oligomeric regulation and functional consequences in DNA replication and genome integrity through approaches that combine in vitro studies, cell culture, and mouse models.
Fu et al., Biochemistry (2013) 52 7050
Fu et al., ChemBioChem (2014) 15 2598
Aye and Weiss labs, Oncogene (2015) 34 2011
Wisitpitthaya et al., ACS Chem Bio (2016) 11 2021
Fu & Long et al. (2017) Under Peer Review (original research)
3) Biophysics and Biochemical Regulation of Redox-Dependent Metalloenzymes
We are investigating the mechanism and regulation of redox-dependent metalloenzymes in isolated systems and in intact mammalian cells.
4) A Chemical Approach to Modulate Protein Trafficking
We are developing a new chemical platform for manipulating intracellular protein trafficking.
Specific Opportunities for Training & Experience in-House
synthetic methodology and new reaction discovery, protein expression/purification, mammalian tissue culture, cloning and gene delivery, lentiviral vector-mediated transduction of short-hairpin RNAs, live-cell imaging (confocal fluorescence & multiphoton excitation microscopy), flow cytometry, immunoprecipitation, quantitative real-time PCR, proteomics analyses, and analogous chemical biology techniques in zebrafish and C. elegans including microinjection techniques.
chemical and chemoenzymatic synthesis, protein expression/purification, enzyme inhibition kinetics, oligomeric state analyses, fluorescence assays (using both synthetic dyes & fluorescent proteins): fluorescence resonance energy transfer (FRET) and fluorescence anisotropy, stopped-flow kinetics, mammalian tissue culture, cloning and gene delivery, fluorescence-activated cell sorting (FACS) analysis, live-cell imaging (confocal fluorescence microscopy), cell-based DNA damage assays, single DNA fiber staining method, RNA-seq analysis, and high-throughput drug discovery.
anaerobic techniques in metalloenzymology, in vitro and whole-cell electron paramagnetic resonance spectroscopy, mammalian tissue culture, cloning, generation and maintenance of stable cell lines, microscopy.
analogous to Program 1.
Additional Training Opportunities through Research Collaborations
- Single particle electron microscopy
- Macromolecular X-ray crystallography
- Animal model studies in mice