Ying Lu
Harvard Medical School
Systems Biology Department
200 Longwood Avenue, WAB 524
Boston, MA 02145
Email: ying_lu@hms.harvard.edu
Website: projects.iq.harvard.edu/yinglu
Summary
Accuracy is a remarkable feature of a large number of biological processes. To maintain homeostasis, cellular protein degradation must be carried out with no less efficiency or precision than transcription and translation. My lab is trying to understand how the cell achieves accurate control of protein degradation and how its failure may lead to neurodegeneration and aging. Using modern enzymological techniques, namely single-molecule fluorescence/force spectroscopy and cryo-electron microscopy, we are investigating how the information in ubiquitin configurations is decoded by the proteasome, a universal protein machine in eukaryotic species, to command an accurate rate of protein degradation.
Publications
Ying Lu, Byung-hoon Lee, Randall King, Daniel Finley and Marc W. Kirschner (2015). Substrate Degradation by the Proteasome: A Single-Molecule Kinetic Analysis. Science, 348:1250834.
Rui Fang, Jason Hon, Mengying Zhou and Ying Lu* (2022). An empirical energy landscape reveals the mechanism of proteasome in polypeptide translocation. eLife. 10.7554/eLife.71911
Donghoon Lee, Yanan Zhu, Louis Colson, Xiaorong Wang, Siyi Chen, Emre Tkacik, Lan Huang, Qi Ouyang, Alfred L. Goldberg* and Ying Lu* (2023) Molecular mechanisms for activation of the 26S proteasome. Molecular Cell Aug 17;83(16):2959-2975.e7
Mengying Zhou, Rui Fang, Louis Colson, Katherine A. Donovan, Moritz Hunkeler, Yuyu Song, Can Zhang, Siyi Chen, Dong-hoon Lee, Gary A. Bradshaw, Robyn Eisert, Yihong Ye, Marian Kalocsay, Alfred Goldberg, Eric S. Fischer, Ying Lu* (2023) HUWE1 Amplifies Ubiquitin Modifications to Broadly Stimulate Clearance of Proteins and Aggregates. BioRxiv 542886 [Preprint]. May 30, 2023. doi.org/10.1101/2023.05.30.542866
Rui Fang*, Luolan Bai, Boyan Li, Kevin Dong, Joao A Paulo, Mengying Zhou, Yi-Chi Chu, Yuyu Song, Michael Sherman, Christine Field, Timothy Mitchison*, Ying Lu* (2024) Episodic Transport of Protein Aggregates Achieves a Positive Size Selectivity in Aggresome Formation. BioRxiv 606767. [Preprint]. Aug. 07, 2024. doi.org/10.1101/2024.08.06.606767
*Co-corresponding author