The Lu group research interests lie at the interface between chemistry and biology. We are developing innovative chemical approaches to gain deeper insight into biological structures and functions, while also taking advantage of recently developed biological tools to advance all areas in chemistry, including analytic, inorganic, organic, physical and materials chemistry.

Specific areas of current interests include

1) Computational design and directed evolution of artificial metalloenzymes as environmentally benign biocatalysts for renewable energy generation and pharmaceutical drug syntheses;

2) Engineer biocatalysts to address challenges in synthetic inorganic and organic chemistry and applications of novel biocatalysts in synthetic biology for biomass conversion, valuable products generation;

3) Design and selection of sensors and imaging agents for metal ions, metabolites and glycoRNAs to advance metallomics, metabolomics and glycomics for medical diagnosis, imaging and therapy in neurodegenerative and infectious diseases, and cancers;

4) Employing principles from biology for directed assembly of nanomaterials with controlled morphologies and its applications in imaging and nanomedicine;

5) Developing novel gene-editing methods to improve sequence fidelity and gene target accessibility.

Yuan Ma, Weijie Guo, Quanbing Mou, Xiangli Shao, Mingkuan Lyu, Valeria Garcia, Linggen Kong, Whitney Lewis, Carson Ward, Zhenglin Yang, Xingxin Pan, S. Stephen Yi, Yi Lu, “Spatial imaging of glycoRNA in single cells with ARPLA",” Nature Biotech (https://doi.org/10.1038/s41587-023-01801-z).

Yuting Wu, Seyed-Fakhreddin Torabi, Ryan J. Lake, Shanni Hong, Zhengxin Yu, Peiwen Wu, Zhenglin Yang, Kevin Nelson, Weijie Guo, Gregory T. Pawel, Jacqueline Van Stappen, Xiangli Shao, Liviu M. Mirica, and Yi Lu. “Simultaneous Fe²⁺/Fe³⁺ imaging shows Fe³⁺ over Fe²⁺ enrichment in Alzheimer’s disease mouse brain,” Science Adv. 9, https://www.science.org/doi/10.1126/sciadv.ade7622 (2023).

Yunling Deng, Sudharsan Dwaraknath, Wenhao O. Ouyang, Cory J. Matsumoto, Stephanie Ouchida, and Yi Lu, “Engineering an Oxygen-Binding Protein for Photocatalytic CO₂ Reductions in Water,” Angew. Chem. Int. Ed. e202215719  (https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202215719) (2023).

Yu Zhou, Dr. Evan N. Mirts, Sangdo Yook, Dr. Matthew Waugh, Rachel Martini, Yong-Su Jin, Yi Lu, “Reshaping the 2-Pyrone Synthase Active Site for Chemoselective Biosynthesis of Polyketides,” Angew Chemie Int. Ed.  62,  e2022124 (https://doi.org/10.1002/anie.202212440) (2023).

Casey Van Stappen, Yunling Deng, Yiwei Liu, Hirbod Heidari, Jing-Xiang Wang, Yu Zhou, Aaron P. Ledray, Yi Lu, "Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere,” Chem. Rev. 122, 14, 11974–12045 (2022).

Quanbing Mou, Xueyi Xue, Yuan Ma, Mandira Banik, Valeria Garcia, Weijie Guo, Jiang Wang, Tingjie Song, Li-Qing Chen, and Yi Lu, “Efficient delivery of a DNA aptamer-based biosensor into plant cells for glucose sensing through thiol-mediated uptake,” Science Adv. 8, DOI: 10.1126/sciadv.abo0902 (2022).

Xiaojing Wang, Gun Kim, James L. Chu, Tingjie Song, Zhenglin Yang, Weijie Guo, Xiangli Shao, Michael L. Oelze, King C. Li and Yi Lu, “Noninvasive and Spatiotemporal Control of DNAzyme-Based Imaging of Metal Ions In Vivo Using High-Intensity Focused Ultrasound,” J. Am. Chem. Soc. 144, 5812–5819 (2022).

JingJing Zhang, Tian Lan, and Yi Lu, “Overcoming Major Barriers to Developing Successful Sensors for Practical Applications Using Functional Nucleic Acids,” Ann. Rev. Anal. Chem. 15, 151-171 (2022).

Yiming Wang, Nitya sai Reddy Satyavolu, Hong Yang, Yi Lu, Kinetic Reconstruction of DNA-Programmed Plasmonic Metal Nanostructures with Predictable Shapes and Optical Properties, J. Am. Chem. Soc. 144, 4410–4421 (2022).

Ana S. Peinetti, Ryan J. Lake, Wen Cong, Laura Cooper, Yuting Wu, Yuan Ma, Gregory T. Pawel, María Eugenia Toimil-Molares, Christina Trautmann, Lijun Rong, Benito Mariñas, Omar Azzaroni, and Yi Lu, “Direct detection of human adenovirus and SARS-CoV-2 with ability to inform infectivity using a DNA aptamer-nanopore sensor,” Science Adv. 7, eabh2848; DOI: 10.1126/sciadv.abh2848 (2021).

Mingkuan Lyu, Linggen Kong, Zhenglin Yang, Yuting Wu, Claire E. McGhee, and Yi Lu, “PNA-Assisted DNAzymes to Cleave Double-Stranded DNA for Genetic Engineering with High Sequence Fidelity,” J. Am. Chem. Soc. 143, 9724–9728 (2021).

Claire E. McGhee, Zhenglin Yang, Weijie Guo, Yuting Wu, Mingkuan Lyu, Cynthia J. DeLong, Shanni Hong, Yuan Ma, Melvin G. McInnis, K. Sue O’Shea, and Yi Lu, “DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons,” ACS Central Science 7, 1809–1820 (2021).

Matthew W. Waugh, Sudharsan Dwaraknath and Yi Lu, “Advances in Metalloprotein Design and Engineering: Strategies Employed and Insights Gained,” In Section 8 (Biocoordination Chemistry) Lawrence Que, Jr. and Yi Lu, eds., Comprehensive Coordination Chemistry III, Edwin C. Constable, Gerard Parkin, Lawrence Que Jr., eds., pp 900-928 (2021).

Ruo-Can Qian, Ze-Rui Zhou, Weijie Guo, Yuting Wu, Zhenglin Yang, and Yi Lu, “Cell Surface Engineering using DNAzymes: Metal Ion-mediated Control of Cell-Cell Interactions,” J. Am. Chem. Soc. 143, 5737–5744 (2021).

Christopher J. Reed, Quan N. Lam,   Evan N. Mirts  and  Yi Lu, “Molecular understanding of heteronuclear active sites in heme–copper oxidases, nitric oxide reductases, and sulfite reductases through biomimetic modelling,” Chem. Soc. Rev. 50, 2486-2539 (2021).

Yuting Wu, Zhenglin Yang and Yi Lu, Photocaged functional nucleic acids for spatiotemporal imaging in biology, Curr. Opin. Chem. Biol. 57, 95-104 (2020).

Ying Xiong, Jingjing Zhang, Zhenglin Yang, Quanbing Mou, Yuan Ma, Yonghua Xiong, and Yi Lu, “Functional DNA Regulated CRISPR-Cas12a Sensors for Point-of-Care Diagnostics of Non-Nucleic Acid Targets,” J. Am. Chem. Soc. 142, 207-213 (2020).

JingJing Zhang, Tian Lan, and Yi Lu, “Translating in vitro Diagnostics from Centralized Laboratories to Point-of-Cares using Commercially-Available Handheld Meters,” Trac-Trends Anal. Chem. 124, 115782 (2020).

Mengyi Xiong, Zhenglin Yang, Ryan J. Lake, Junjie Li, Shanni Hong, Huanhuan Fan, Xiao-Bing Zhang and Yi Lu, “DNAzyme-Mediated Genetically Encoded Sensors for Ratiometric Imaging of Metal Ions in Living Cells, Angew. Chemie Int. Ed. 132, 1907-1912 (2020).

Ryan J. Lake, Zhenglin Yang, JingJing Zhang, Yi Lu, “DNAzymes as Activity-Based Sensors for Metal Ions: Recent Applications, Demonstrated Advantages, Current Challenges, and Future Directions,” Acc. Chem. Res. 52, 3275-3286 (2019).

Lele Li, Hang Xing, Jingjing Zhang, and Yi Lu, “Functional DNA Molecules Enable Selective and Stimuli-Responsive Nanoparticles for Biomedical Applications,” Acc. Chem. Res. (special issue “Nanomedicine and Beyond”), 52, 2415-2426 (2019).

Evan N. Mirts, Ambika Bhagi-Damodaran, and Yi Lu, “Understanding and Modulating Metalloenzymes with Unnatural Amino Acids, Non-Native Metal Ions, and Non-Native Metallocofactors,” Acc. Chem. Res. (Special Issue on “Artificial Metalloenzymes and Abiological Catalysis of Metalloenzymes”) 52, 935–944 (2019).

Zhenglin Yang, Kang Yong Loh, Yueh-Te Chu, Ruopei Feng, Nitya Sai Reddy Satyavolu, Mengyi Xiong, Stephanie M. Nakamata Huynh, Kevin Hwang, Lele Li, Hang Xing, Xiaobing Zhang, Yann R. Chemla, Martin Gruebele, and Yi Lu, “Optical Control of Metal Ion Probes in Cells and Zebrafish Using Highly Selective DNAzymes Conjugated to Upconversion Nanoparticles, J. Am. Chem. Soc. 140, 17656–17665 (2018).

Evan N. Mirts, Igor D. Petrik, Parisa Hosseinzadeh, Mark J. Nilges, and Yi Lu, “A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme,” Science 361, 1098-1101 (2018).

Dr. Lu has received many research and teaching awards, including the Howard Hughes Medical Institute Professors Award (2002), Fellow of American Association for the Advancement of Science (2007), Fellow of the Royal Society of Chemistry (2015), Royal Society of Chemistry Applied Inorganic Chemistry Award (2015), Joseph Chatt Award (2020) and Fellow of the National Academy of Inventors (2021) and Allen Distinguished Investigators (2022).

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