Personal Profile

Li Mingtao, a second-level professor in the Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, is a doctoral supervisor. He serves as the director of the Guangdong Key Laboratory of Brain Function and Brain Diseases, the director of the Proteomics Research Center of Zhongshan School of Medicine, and the director of the Guangdong Provincial Key Laboratory of Proteomics in Translational Medicine in Ordinary Universities. He obtained his Ph.D. in Pharmacology from Sun Yat-sen University in 1996 and conducted two years of postdoctoral research at the University of Colorado, USA in 1999.

Professor Li has long been engaged in pharmacology and molecular neurobiology research. His main research areas include neuronal apoptosis and its signal transduction, the mechanisms and new therapeutic targets of Parkinson's disease, and proteomics. His research findings are of great significance for revealing the essence of the occurrence of neurodegenerative diseases, finding and establishing drug targets, and further effectively preventing and treating neurodegenerative diseases.

After returning to China in 2001, Professor Li received a total of more than 13 million yuan in funding from the 985 and 211 discipline construction projects. He established a well-equipped, highly efficient, and rationally structured molecular neurobiology laboratory (located at Room 1044, West 10th Floor, Science and Technology Building, Zhongshan School of Medicine). The laboratory is equipped with advanced instruments necessary for molecular biology experiments and research on new therapeutic targets for Parkinson's disease.

Focusing on the research of the mechanisms and new targets of Parkinson's disease, Professor Li has obtained funding for more than twenty projects as the principal investigator, including key projects of the National Natural Science Foundation of China, major special projects for "Significant New Drug Development" in science and technology, the "973" Program, the Class B Outstanding Young Scholars Project of the National Natural Science Foundation of China, jointly funded projects of the National Natural Science Foundation of China and the Guangdong Provincial Government, key area R & D programs of the Guangdong Provincial Department of Science and Technology, and key team projects of the Guangdong Provincial Natural Science Foundation. Among them, in 2018, he received two major projects: the Integrated Project of the National Natural Science Foundation of China - Guangdong Joint Fund (U1801681, 11.8 million yuan) and the Special Project on "Brain Science and Brain-like Research" of the Key Area R & D Program of the Guangdong Provincial Department of Science and Technology (2018B030337001, 44.8 million yuan).

In addition, Professor Li established the first proteomics research center in Guangdong Province as the principal investigator and has been conducting translational medicine research for a long time, benefiting more than 180 clinical projects. Based on this platform, he applied for and obtained the "Guangdong Provincial Key Laboratory of Proteomics in Translational Medicine in Ordinary Universities" in 2011, thus filling the gap that there has been no key laboratory in the national key discipline of pharmacology at Sun Yat-sen University. The proteomics research center is located on the 10th floor of the How Mother Building. For more details, please visit http://proteomics.sysu.edu.cn/.

In recent years, Professor Li's research group has published more than 40 SCI papers. Among them, as the first author or corresponding author, he has published more than 30 papers in international core journals such as J Neurosci, Mol Cell Biol, J Biol Chem, Cell Death Differ, Proteomics, and Neuropharmacology. He also published relevant review articles in Drug News Perspect.

Based on the above research achievements, as the first completer, Professor Li won the First Prize of the Excellent Scientific Research Achievements Award of Higher Education Institutions (Ministry of Education) in 2011 and the First Prize of the Guangdong Science and Technology Awards in 2011.

Academic Achievements

Important Academic Research Achievements and Contributions

Professor Li's work mainly focuses on elucidating the signal transduction pathways of neuronal apoptosis, revealing the pathogenesis of Parkinson's disease (PD) and establishing new drug targets. He was the first to confirm that JNK is a new therapeutic target for PD (Wang et al., 2004, Neurosci Res; Wang et al., 2004, Drug News Perspect). He searched from the source, screened, and established that dp5, ATF3, and caspase-3 are pro-apoptotic target genes of JNK/c-Jun (Ma et al., 2007, J Biol Chem; Mei et al., 2008, Neuroscience; Song et al., 2011, Neurosci Lett). Moreover, he revealed the rule that "the dimer of c-Jun/ATF2 binds to the ATF site to activate the expression of pro-apoptotic target genes" (Yuan et al., 2009, Mol Cell Biol). This provides a theoretical basis for further research on the mechanism by which the JNK-c-Jun pathway mediates the occurrence of PD and a scientific basis for establishing new therapeutic targets for PD.

Professor Li was the first to discover that PKA and CaMKII mediate the phosphorylation of Ser9 of GSK-3β in different models respectively (Li et al., 2000, Mol Cell Biol; Song et al., 2010, J Biol Chem), thereby promoting neuronal survival. Recently, he also reported that phosphorylation at Ser9/Ser389 inhibits the cleavage of GSK-3β by the protease Calpain during neuronal death (Ma et al., 2012, J Biol Chem). In addition, he was the first to confirm that GSK-3 is a new therapeutic target for PD (Wang et al., 2007, Neuropharmacology). He proposed a new idea of "targeting JNK/GSK-3 for the treatment of PD", and further proposed a "two-birds-with-one-stone" treatment strategy of simultaneously blocking these two key pro-apoptotic proteins with a single drug. He also found compounds that can effectively inhibit both JNK/c-Jun and GSK-3 simultaneously (Xie et al., 2004, Neurosci Lett), pointing out a new direction for the research and development of PD drugs.

Furthermore, Professor Li was the first to use proteomics methods to search for new substrates of Calpain from the source when neurons undergo apoptosis. He successfully identified 12 already reported and 7 newly reported new Calpain substrate proteins. Among them, the products of CRMP-3 and CRMP-4 cleaved by Calpain have pro-apoptotic effects on neurons (Liu et al., 2009, Proteomics), laying the foundation for establishing Calpain as a therapeutic target for neurodegenerative diseases.

Recently, Professor Li reported that the transcriptional upregulation of the BH3-only pro-apoptotic transcription factor Bim is not mediated by c-Jun, FOXO1/3a, B/C-Myb, etc., which have been reported, but is directly transcriptionally activated by the transcription factor Egr-1, thus triggering neuronal apoptosis (Xie et al., 2011, J Neurosci). This new discovery immediately solved the mystery of why GC-rich DNA inhibitors such as Mithramycin A and Chromomycin can protect neurons, namely: these drugs play a neuroprotective role by directly inhibiting the transcriptional activation of the Bim gene by Egr-1. This achievement not only provides more sufficient scientific evidence for establishing Egr-1/Bim as a therapeutic target for neurodegenerative diseases but also has very important guiding significance for exploring the treatment of neurodegenerative diseases with GC-rich DNA inhibitors.

Publications as the First/Corresponding Author (SCI Papers)

Corresponding Author

1. Chen W, Huang Q, Ma S#, Li M#: Progress in dopaminergic cell-replacement and regenerative strategies for Parkinson’s disease. ACS Chem Neurosci 2018 in press.
2. Yu Q, Huang Q, Du X, Xu S, Li M# and Ma S#. Early activation of Egr-1 promotes neuroinflammation and dopaminergic neurodegeneration in an experimental model of Parkinson's disease. Exp Neurol. 2018, 302:145-154.
3. Huang Q, Du X, He X, Yu Q, Hu K, Breitwieser W, Shen Q, Ma S#, Li M#. Jnk-mediated activation of atf2 contributes to dopaminergic neurodegeneration in the mptp mouse model of parkinson's disease. Exp Neurol. 2016, 277:296-304.
4. Wu R, Chen H, Ma J, He Q, Huang Q, Liu Q, Li M#, Yuan Z#. C-abl-p38alpha signaling plays an important role in mptp-induced neuronal death. Cell Death Differ. 2016, 23(3):542-552.
5. Ma S, Liu S, Huang Q, Xie B, Lai B, Wang C, Song B, and Li M#. Site-specific phosphorylation protects GSK-3β from calpain-mediated truncation of its N- and C-termini. J Biol Chem. 2012;287:22521-32
6. Xie B, Wang C, Zheng Z, Song B, Ma C, Thiel G, and Li M#. Egr-1 transactivates Bim gene expression to promote neuronal apoptosis. J Neurosci.2011; 31:5032-5044
7. Song B, Lai B, Zheng Z, Zhang Y, Luo J, Wang C, Chen Y, Woodgett J, and Li M#. Inhibitory phosphorylation of GSK-3 by CaMKII couples depolarization to neuronal survival. J Biol Chem.2010;285:41122-34.
8. Yuan Z, Gong S, Luo J, Zheng Z, Song B, Ma S, Guo J, Hu C, Thiel G, Vinson C, Hu CD, Wang Y, Li M#. Opposing roles for ATF2 and c-Fos in c-Jun-mediated neuronal apoptosis. Mol Cell Biol. 2009;29:2431-2442.
9. Liu W, Zhou XW, Liu S, Hu K, Wang C, He Q, Li M#. Calpain-truncated CRMP-3 and -4 contribute to potassium deprivation-induced apoptosis of cerebellar granule neurons. Proteomics. 2009;9:3712-3728.
10. Ma C, Ying C, Yuan Z, Song B, Li D, Liu Y, Lai B, Li W, Chen R, Ching YP, Li M#. dp5/HRK is a c-Jun target gene and required for apoptosis induced by potassium deprivation in cerebellar granule neurons. J Biol Chem. 2007;282:30901-30909.
11. Song B, Xie B, Wang C, Li M#. c-Jun induction is independent of Egr during cerebellar granule neuron apoptosis. Neuroreport. 2012; 23:67-72.
12. Song B, Xie B, Wang C, Li M#. Caspase-3 is a target gene of c-Jun:ATF2 heterodimers during apoptosis induced by activity deprivation in cerebellar granule neurons. Neurosci Lett. 2011; 505:76-81.
13. Mei Y, Yuan Z, Song B, Li D, Ma C, Hu C, Ching YP, Li M#. Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons. Neuroscience. 2008;151:771-779.
14. Wang W, Yang Y, Ying C, Li W, Ruan H, Zhu X, You Y, Han Y, Chen R, Wang Y, Li M#. Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. Neuropharmacology. 2007;52:1678-1684.
15. Yuan Z, Mei Y, Zhou J, Tan M, Song B, Ma C, Ying C, Li D, Ching YP, Li M#. E2F1 is not essential for apoptosis induced by potassium deprivation in cerebellar granule neurons. Neurosci Lett. 2007;424:155-159.
16. Song B, Ma C, Gong S, Yuan Z, Li D, Liu W, Li W, Chen R, Zhu X, Zeng J, Han Y, Li M#. Extracellular signal-regulated kinases are not involved in activity-dependent survival or apoptosis in cerebellar granule neurons. Neurosci Lett. 2006;407:214-218.
17. Yang LL, Liu XQ, Liu W, Cheng B, Li M#. Comparative analysis of whole saliva proteomes for the screening of biomarkers for oral lichen planus. Inflamm Res. 2006;55:405-407.
18. Shi L, Gong S, Yuan Z, Ma C, Liu Y, Wang C, Li W, Pi R, Huang S, Chen R, Han Y, Mao Z, Li M#. Activity deprivation-dependent induction of the proapoptotic BH3-only protein Bim is independent of JNK/c-Jun activation during apoptosis in cerebellar granule neurons. Neurosci Lett. 2005;375:7-12.
19. Xie Y, Liu Y, Ma C, Yuan Z, Wang W, Zhu Z, Gao G, Liu X, Yuan H, Chen R, Huang S, Wang X, Zhu X, Mao Z, Li M#. Indirubin-3'-oxime inhibits c-Jun NH2-terminal kinase: anti-apoptotic effect in cerebellar granule neurons. Neurosci Lett. 2004;367:355-359.
20. Wang W, Shi L, Xie Y, Ma C, Li W, Su X, Huang S, Chen R, Zhu Z, Mao Z, Han Y, Li M#. SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease. Neurosci Res. 2004;48:195-202.
21. Wang W, Ma C, Mao Z, Li M#. JNK inhibition as a potential strategy in treating Parkinson's disease. Drug News Perspect. 2004;17:646-654.
22. Li M, Linseman DA, Allen MP, Meintzer MK, Wang X, Laessig T, Wierman ME, Heidenreich KA. Myocyte enhancer factor 2A and 2D undergo phosphorylation and caspase-mediated degradation during apoptosis of rat cerebellar granule neurons. J Neurosci. 2001;21:6544-6552.
23. Li M, Wang X, Meintzer MK, Laessig T, Birnbaum MJ, Heidenreich KA. Cyclic AMP promotes neuronal survival by phosphorylation of glycogen synthase kinase 3beta. Mol Cell Biol. 2000;20:9356-9363.

Awards and Honors

1. As the first completer, won the First Prize of the Excellent Scientific Research Achievements Award of Higher Education Institutions (Ministry of Education) in 2011.
2. As the first completer, won the First Prize of the Guangdong Science and Technology Awards in 2011.

Academic Part-time Positions

1. Member of the 12th Expert Review Panel of the National Natural Science Foundation of China.
2. Chairman of the Professional Committee of Neuropharmacology, Guangdong Pharmacological Society.