How do chemical imbalances make the brain vulnerable in Alzheimer’s disease and other disorders?
My research investigates how redox and metabolic imbalance contributes to brain vulnerability. I develop nucleic acid–based sensors and sequencing strategies that measure metal ions and metabolites in living systems with cellular precision. Using these tools, I revealed oxidation state–specific changes in iron near amyloid pathology and their association with neuroinflammation and memory decline. Building on this foundation, my independent program will integrate chemical biology, bioinformatics, and advanced imaging to define how redox imbalance drives protein aggregation and selective neuronal and glial vulnerability. By bridging molecular innovation with neuroscience, I aim to transform precise chemical measurements into biological insight, stage-specific biomarkers, and therapeutic opportunities.
Research Highlights
Iron Redox in Alzheimer’s Disease
How does iron imbalance drive selective neuronal vulnerability?
Sequencing Chemistry and Gene Regulation
How can metal ions and metabolites be linked to gene regulation?
Nucleic Acid Sensors Across Biology
How can nucleic acids be engineered as molecular sensors?
Selected Publications
Wu, Y.*; Torabi, S.-F.*; Lake, R. J.*; Hong, S.; Yu, Z.; Wu, P.; Yang, Z.; Nelson, K.; Guo, W.; Pawel, G. T.; Van Stappen, J.; Shao, X.; Mirica, L. M.; Lu, Y. Simultaneous Fe2+/Fe3+ Imaging Shows Fe3+ over Fe2+ Enrichment in Alzheimer’s Disease Mouse Brain. Science Advances 2023, 9 (16), eade7622.
Wu, Y.; Kong, W.; Van Stappen, J.; Kong, L.; Huang, Z.; Yang, Z.; Kuo, Y.-A.; Chen, Y.-I.; He, Y., Yeh, H.-C.; Lu, T.; Lu, Y. Genetically Encoded Fluorogenic DNA Aptamers for Imaging Metabolite in Living Cells. J. Am. Chem. Soc. 2025, 147, 2, 1529–1541.
Xiong, M.*; Wu, Y.*; Kong, G.; Lewis, W.; Yang, Z.; Zhang, H.; Xu, L.; Liu, Y.; Liu, Q.; Zhao, X.; Zhang, X.B.; Lu Y. A Semisynthetic Bioluminescence Sensor for Ratiometric Imaging of Metal Ions In Vivo Using DNAzymes Conjugated to An Engineered Nano-Luciferase. Angew. Chem., Int. Ed. 2023, e202308086.
Wu, Y.*; Lewis, W.*; Wai, J.L.*; Xiong, M.; Zheng, J.; Yang, Z.; Gordon, C.; Lu, Y.; New, S.Y.; Zhang, X.B.; Lu, Y. Ratiometric Detection of Zn2+ Using DNAzyme-Based Bioluminescence Resonance Energy Transfer Sensors. Chemistry 2023, 5(3), 1745-1759.
Remesal, L.; Sucharov-Costa, J.; Wu, Y.; Pratt, K. J.B.; Bieri, G.; Philp, A.; Phan, M.; Aghayev, T.; White, C. W.; Wheatley, E. G.; Zou, B.; Desousa, B. R.; Couthouis, J.; Jian, I. H.; Xie, X. S.; Lu, Y.; Maynard, J. C.; Burlingame, A. L.; Villeda, S. A. Targeting Iron-Associated Protein FTL1 in the Brain of Old Mice Improves Age-Related Cognitive Impairment. Nat. Aging. 2025.
Banik, M.; Ledray, A.P.; Wu, Y.; Lu, Y. Delivering DNA Aptamers Across the Blood–Brain Barrier Reveals Heterogeneous Decreased ATP in Different Brain Regions of Alzheimer’s Disease Mouse Models. ACS Cent. Sci. 2024.
McGhee, C. E.*; Yang, Z.*; Guo, W.*; Wu, Y.; Lyu, M.; DeLong, C. J.; Hong, S.; Ma, Y.; McInnis, M. G.; O’Shea, K. S.; Lu, Y. DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons. ACS Cent. Sci. 2021, 7 (11), 1809–1820.
Wang, J.*; Wu, Y.*; Zhao, F.*; Wu, Y.; Dong, W.; Zhao, J.; Zhu, Z.; Liu, D. Fgf-Signaling-Dependent Sox9a and Atoh1a Regulate Otic Neural Development in Zebrafish. J. Neurosci. 2015, 35 (1), 234–244.