My lab studies biological consequences of oxidative stress spanning multiple scales of complexity from individual molecules to whole cells. Conditions such as neurodegeneration, ionizing radiation exposure, chemical exposures, and desiccation have complex impacts on biomolecules and cells, often challenging viability by affecting multiple loci and processes. We seek to elucidate mechanisms of toxicity, resistance, and response to oxidative stress and engineer translational protein and metabolic interventions. We approach these problems through: 1) protein-structure-resolved, genome-scale metabolic network modeling and multi-omics measurements of microenvironmental stress phenotypes, 2) machine learning of modifications to protein structure caused by stress exposures, and 3) engineering proteins to alter how they are impacted by stress. Gaining understanding and control over biological stability under stress has far-reaching implications, such as prognostic markers and improved cancer treatment, systems-level understanding of neurodegeneration, engineering industrial and therapeutic microbes, developing drought resistant crops, and broadly developing biotechnologies tailored to specific environmental conditions.

For a complete list see: https://scholar.google.com/citations?user=y2BA7ToAAAAJ&hl=en 

† corresponding author | * contributed equally 

Veling MT*, Nguyen DT*, Thadani NN, Oster ME, Rollins NJ, Brock KP, Bethel NP, Lim S, Baker D, Way JC, Marks DS, Chang RL†, Silver PA†. Natural and designed proteins inspired by extremotolerant organisms can form condensates and attenuate apoptosis in human cells. ACS Synth Biol. 2022 Mar 18;11(3):1292-1302. doi: https://doi.org/10.1021/acssynbio.1c00572

Chang RL†, Stanley JA, Robinson MC, Sher JW, Li Z, Chan YA, Omdahl AR, Wattiez R, Godzik A, Matallana-Surget S†. Protein structure, amino acid composition and sequence determine proteome vulnerability to oxidation-induced damage. EMBO J. 2020, Oct 19; e104523. doi: https://doi.org/10.15252/embj.2020104523

Brunk E, Chang RL, Xia J, Hefzi H, Yurkovich JT, Kim D, Buckmiller E, Wang HH, Cho BK, Yang C, Palsson BO, Church GM†, Lewis NE†. Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow. Proc Natl Acad Sci U S A. 2018, Oct 23; 115(43):11096-11101. doi: https://doi.org/10.1073/pnas.1811971115

Chang RL, Xie L, Bourne PE, Palsson B؆. Antibacterial mechanisms identified through structural systems pharmacology. BMC Syst Biol. 2013, Oct 10; 7:102. doi: https://doi.org/10.1186/1752-0509-7-102

Chang RL, Andrews K, Kim D, Li Z, Godzik A, Palsson B؆. Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli. Science. 2013, Jun 7; 340(6137):1220-1223. doi: https://doi.org/10.1126/science.1234012

Chang RL, Ghamsari L, Manichaikul A, Hom EF, Balaji S, Fu W, Shen Y, Hao T, Palsson BØ, Salehi-Ashtiani K†, Papin JA†. Metabolic network reconstruction of Chlamydomonas offers insight into light-driven algal metabolism. Mol Syst Biol. 2011, Aug 2; 7:518. doi: https://doi.org/10.1038/msb.2011.52

Chang RL, Xie L, Xie L, Bourne PE, Palsson B؆. Drug off-target effects predicted using structural analysis in the context of a metabolic network model. PLoS Comput Biol. 2010, Sep 23; 6(9):e1000938. doi: https://doi.org/10.1371/journal.pcbi.1000938