1992.09 - 1996.06 Beijing Normal University, BS in Biochemistry

1996.07 - 1998.09 Institute of Biophysics CAS, Research Assistant

1998.09 - 2003.07 Institute of Biophysics CAS, PhD in Biochemistry & Molecular Biology

2002.10 - 2003.01 INSERM U-128 France, Research collaboration

2003.12 - 2009.06 UT Southwestern Medical Center at Dallas, Postdoctoral Fellow

2009.07 - 2014.12 Institute of Biophysics CAS, Associate Investigator

2015.01 - 2019.12 Institute of Biophysics CAS, Project Investigator

2016.09 - present University of Chinese Academy of Science, Professor

2020.01 - present Institute of Biophysics CAS, Principal Investigator

2007 Postdoctoral fellow nominee by UT Southwestern Graduate School of Biomedical Sciences for participation in the AAAS/Science Program for Excellence in Science

2006 Dystonia Medical Research Foundation Cure Dystonia Initiative Fellowship

2001 "Liu Yongling" Awards of CAS

1996 Outstanding Graduate Award of Beijing

With the dramatic increase in the aging population and social life pressure worldwide, neurodegenerative diseases and neuropsychiatric disorders are becoming major public health crises. Neurodegenerative diseases include a large group of neurologic syndromes caused by the progressive loss of structure or function of neurons in the brain or peripheral nervous system, ultimately leading to cell death. Neurodegenerative diseases are often classified into two categories, one affects cognition and memory, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), and the other involves movements, such as Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). In addition, neuropsychiatric disorders, such as depression, schizophrenia, and bipolar disorder, promote the development of cognitive impairment, even causing AD. Cognitive impairments and movement disorders are often co-morbid. Thus, studying the common mechanism underlying these two groups of brain disorders is the key to understanding neurodegenerative diseases.

We have focused on understanding molecular and cellular mechanisms underlying cognitive impairments, movement disorders, and related brain diseases. Current research includes three directions: (1) Aiming to explore the common mechanism underlying cognitive impairments and movement disorders, we have systematically investigated the involvement of RNA-binding proteins (TDP-43 and FUS) in neurodegeneration using the transgenic fly model we established and mouse models along with multi-disciplinary approaches, mainly focusing on the mitochondrial impairment resulting from the disease-associated mutations ultimately causing neuronal death. (2) Through collaborations with clinical hospitals, we are developing non-invasive/mini-invasive detection methods based on the specific biomarkers of various neurodegenerative diseases from different patient samples, including the central nervous system and peripheral tissues. (3) We are screening for compound/drug candidates that postpone disease progression using the microfluidic chamber and animal models for these brain diseases. Such studies will provide new insights into pathogenic mechanisms underlying these brain disorders and fundamental information for developing early diagnostic tools and therapeutic approaches.

1. Ma J, Wu JY*,Zhu L*. Detection of orthologous exons and isoforms using EGIO.Bioinformatics. 2022 Sep 30; 38(19):4474-4480.

2. Luan M, Sun Y, Chen J, Jiang Y, Li F, Wei L, Sun W, Ma J, Song L, Liu J, Liu B, Pei Y, Wang Z*,Zhu L*, Deng J*. Diagnostic value of salivary real-time quaking-induced conversion in Parkinson's disease and multiple system atrophy.Mov Disord. 2022 May; 37(5):1059-1063.

3. Chen P, Liu Z, Zhang Q, Lin D, Song L, Liu J, Jiao H, Lai X, Zou S, Wang S, Zhou T, Li B,Zhu L*, Pan B*, Fei E*. DSCAM deficiency leads to premature spine maturation and autism-like behaviors.J Neurosci. 2022 Jan 26; 42(4):532-551.

4. Shi L, Xu A,Zhu L*. Protein aggregation and phase separation in TDP-43 associated neurodegenerative diseases.Prog Biochem Biophys. 2022 Jan; 49(1):8-22.

5. Wang F, Chen X, Cheng H, Song L, Liu J, Caplan S,Zhu L*, Wu JY*. MICAL2PV suppresses the formation of tunneling nanotubes and modulates mitochondrial trafficking.EMBO Rep. 2021 Jul 5; 22(7):e52006.

6. Wang F, Zhang Y,Zhu L*. Tunneling nanotube: a novel type of signal transmission in nervous system.Prog Biochem Biophys. 2021 Jan; 48(1):54-63.

7. Wang P^#, Deng J^#, Jie Dong, Jianghong Liu, Eileen Bigio, Marsel Mesulam, Warren McGee, Xiaoping Chen, Kazuo Fushimi,Zhu L*, Wu JY*. TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response.PLoS Genet. 2019 May 17; 15(5):e1007947.

8. Deng J^#, Wang P^#, Chen X, Cheng H, Liu J, Fushimi K,Zhu L*, Wu JY*. FUS interacts with ATP synthase beta subunit and induces mitochondrial unfolded protein response in cellular and animal models.Proc Natl Acad Sci USA. 2018 Oct 9; 115(41):E9678-86.

9. Zhang Y, Chen M, Qiu Z, Hu K, McGee W, Chen X, Liu J,Zhu L*, Wu JY*. MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2.Protein Cell. 2016 Jul; 7(7):489-500.

10.Zhu L*, Deng J, Wang P, Liu J, Wu JY*. 2016 Mitochondrial damage induced by RNA binding proteins which are associated with neurodegenerative diseases.Prog Biochem Biophys. 2016, 43(4):374-382.

11. Kong R^#, Yi F^#, Wen P, Liu J, Chen X, Ren J, Li X, Shang Y, Nie Y, Wu K, Fan D,Zhu L*, Feng W*, Wu JY*. Myo9b is a key player in SLIT/ROBO-mediated lung tumor suppression.J Clin Invest. 2015 Nov 3; 125(12):4407-4420.

12. Deng J, Yang M, Chen Y, Chen X, Liu J, Sun S, Cheng H, Li Y, Bigio EH, Mesulam M, Xu Q, Du S, Fushimi K,Zhu L*, Wu JY*. FUS Interacts with HSP60 to Promote Mitochondrial Damage.PLoS Genet. 2015 Sep 3; 11(9): e1005357.

13.Zhu L^#, Xu M^#, Yang M, Yang Y, Li Y, Deng J, Ruan L, Liu J, Du S, Liu X, Feng W, Fushimi K, Bigio EH, Mesulam M, Wang C*, Wu JY*. An ALS-mutant TDP-43 neurotoxic peptide adopts an anti-parallel b-structure and induces TDP-43 redistribution.Hum Mol Genet. 2014 Dec 20; 23(25):6863-6877.

14. Zhu K, Chen X, Liu J, Ye H,Zhu L*, Wu JY*. AMPK interacts with DSCAM and plays an important role in Netrin-1 induced neurite outgrowth.Protein Cell. 2013 Feb; 4(2):155-161.

15. Chen M, Deng J, Yang M, Kuo D, Zhu K, Liu J,Zhu L*, Wu JY*. Noncoding RNAs, neurodevelopment, and neurodegeneration. In Posttranscriptional Gene Regulation: RNA Processing in Eukaryotes (Wu JY eds), 1. Edition 2013 Jun; ISBN 978-3-527-32202-2 Wiley-VCH, Weinheim.

16.Zhu L*, Liu J, Wu JY. Impaired post-transcriptional regulation in Alzheimer's disease.Prog Biochem Biophys. 2012, 39:703-708.

17.Zhu L*, Millen L, Mendoza JL, Thomas PJ*. A unique redox-sensing sensor-II motif in torsinA plays a critical role in nucleotide and partner binding.J Biol Chem. 2010 Nov 26; 285:37271-37280.

18.Zhu L, Wrabl JO, Hayashi AP, Rose LS, Thomas PJ*. The torsinA-family AAA+ protein OOC-5 contains a critical disulfide adjacent to sensor-II that couples redox state and nucleotide binding.Mol Biol Cell. 2008 Aug; 19(8):3599-3612.

19.Zhu L, Qin ZJ, Zhou JM*, Kihara H*. Unfolding kinetics of dimeric creatine kinase measured by stopped-flow small angle X-ray scattering.Biochimie. 2004 Feb; 86(2):127-132.

20.Zhu L, Zhang XJ, Wang LY, Zhou JM*, Perrett S*. Relationship between stability of folding intermediates and amyloid formation for the yeast prion Ure2p.J Mol Biol. 2003 Apr 18; 328(1):235-254.

21.Zhu L, Kihara H, Kojima M, Zhou JM*, Perrett S*. Small angle X-ray scattering study of the yeast prion Ure2p.Biochem Biophys Res Commun. 2003 Nov 14; 311(2):525-532.

22.Zhu L, Fan YX, Zhou JM*. Identification of equilibrium and kinetic intermediates involved in folding of urea-denatured creatine kinase.Biochim Biophys Acta. 2001 Jan 12; 1544(1-2):320-332.

(From Li Zhu, April 4, 2023)