CIMR-Shan Lu

Research Group

Shan Lu

lushan(at)cimrbj.ac.cn

Assistant Investigator

Amyotrophic Lateral Sclerosis (ALS),

Frontotemporal Dementia (FTD), Parkinson's Disease (PD),

Gene and Cell Therapy, RNA Binding Protein Phase Separation

lushan(at)cimrbj.ac.cn

B.C., Biology, Nankai University, China

Ph.D., Biochemistry and Molecular Biology, National Institute of Biological Science, Beijing, China

Work Experience

2026-Present

Assistant Investigator, Chinese Institute for Molecular and Cellular Therapeutics, Chinese Institutes for Medical Research, Beijing, China

2022-2026

Senior Scientist, Altos Labs Inc, San Diego, USA

2017-2022

Postdoctoral Researcher, Neuroscience and Cell Biology, University of California, San Diego, USA

Research Interests

The Lu laboratory at CIMR works on neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD). Lu lab aims at elucidating the mechanism of neurodegenerative diseases, developing new therapies and identifying biomarkers for disease diagnosis. Lu lab is focusing on the following directions:

1. Identifying the mechanisms ofhow abnormal RNA binding protein aggregation leads to neurodegeneration;

2. Developing gene therapy and cell therapy-basedmethods to treat neurodegenerative diseases;

3. Identifying novel biomarkers for early disease diagnosis and precision medicine.

Major Contributions

1. Established cellular models that recapitulate TDP-43 pathology found in ALS and FTD patients (Neuron, 2019; Science, 2021)

2. Identifed the mechanisms regulating the formation of TDP-43 pathological inclusions, with the discovery of crucial modulators of TDP-43 de-mixing and toxicity (Nature Cell Biology, 2022; Nature Cell Biology, 2025)

3. Developed proteomic analysis techniques for sensitive identification of therapeutic targets and disease-specific biomarkers (Nature Methods, 2015; Biophysics Reports, 2018; Journal of Proteome Research, 2024)

Representative Publications *：Co-first author; #：Co-corresponding author

Lu, S^#., Zhang S., Oung S., Zhang K., Yates, J.R., and Cleveland, D.W^#. TDP-43 skein-like inclusions are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins. Nature Cell Biology, 2025, 27: 1925–1937. DOI: 10.1038/s41556-025-01789-5

Lu, S., Hu, J. Aladesuyi, B., Goginashvili, A. Vazquez-Sanchez, S., Diedrich, J., Gu, J., Blum, J., Oung, S., Yu, H., Ravits, J., Liu, C., Yates, J.R., and Cleveland, D.W. Heat shock chaperone HSPB1 regulation of cytoplasmic TDP-43 de-mixing and liquid-to-gel transition. Nature Cell Biology, 2022, 24: 1378-1393. DOI: 10.1038/s41556-022-00988-8

Lu, S., Ye, Q., Singh, D., …, Villa, E., Cleveland, D. W., & Corbett, K. D. The SARS-CoV-2 Nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nature Communications, 2021, 12: 1-15. DOI: 10.1038/s41467-020-20768-y

Gasset-Rosa, F.*, Lu, S.*, Yu, H. Y.*, Chen, C.*, Melamed, Z., Guo, L., Shorter, J., Da Cruz, S., Cleveland, D. W. Cytoplasmic TDP-43 de-mixing independent of stress granules drives inhibition of nuclear import, loss of nuclear TDP-43, and cell death. Neuron, 2019, 102: 339-357. DOI: 10.1016/j.neuron.2019.02.038

Yu, H., Lu, S., Gasior, K., Singh, D., Vazquez-Sanchez, S., Tapia, O., ... & Cleveland, D. W. HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science, 2020, 371: eabb4309. DOI: 10.1126/science.abb4309

Lu, S., Fan, S.-B., Yang, B., Li, Y.-X., Meng, J.-M., Wu, L., Li, P., Zhang, K., Zhang, M.-J., and Fu, Y. Mapping native disulfide bonds at a proteome scale. Nature Methods, 2015, 12: 329-331. DOI: 10.1038/nmeth.3283

Lu, S., Cao, Y., Fan, S.B., Chen, Z.L., Fang, R.Q., He, S.M. and Dong, M.Q. Mapping disulfide bonds from sub-micrograms of purified proteins or micrograms of complex protein mixtures. Biophysics Reports, 2018, 4: 68-81. DOI: 10.1007/s41048-018-0050-6

Ye, J.-B., He, X.-N., Wang, S.-J., Dong, M.-Q., Feng, W., Lu, S.^#, and Feng, F.-L.^# Test-time training for deep MS/MS spectrum prediction improves peptide identification. Journal of Proteome Research, 2024, 23: 550-559. DOI: 10.1021/acs.jproteome.3c00229

Zhu, X., Lu, J., Hu, X., Jin, T., Lu, S., & Feng, F. Hierarchical progressive learning for zero-shot peptide-HLA binding prediction and automated antigenic peptide design. Cell Reports, 2025, 44: 115763. DOI: 10.1016/j.celrep.2025.115763

Wu, J., Yan, Z., Li, Z., Qian, X., Lu, S., Dong, M., Zhou, Q., and Yan, N. Structure of the voltage-gated calcium channel Cav1. 1 at 3.6 Å resolution. Nature, 2016, 537: 191–196. DOI: 10.1038/nature19321