个人简介

        王金凯是中山大学引进的教授，博士生导师。2005年毕业于武汉大学生命科学学院获得理学学士学位。2010年毕业于中国科学院昆明动物研究所获得遗传学博士学位（师从宿兵研究员）。2010年至2016年分别在美国爱荷华大学（2010~2012）和加州大学洛杉矶分校（2013~2016）邢毅教授实验室从事生物信息学方向博士后研究。2016年获聘中山大学引进人才。2018年入选广东省珠江人才计划“青年拔尖人才”。       
       实验室成立以来已经以通讯作者身份在Molecular Cell （2篇）、Nature Chemical Biology、 Nature Communications, Nucleic Acids Research（2篇）、Genome Biology等杂志发表论文11篇。

       实验室主要研究兴趣是利用第二代以及第三代高通量测序技术结合生物信息学、基因组学和分子生物学的方法开发m6A修饰的检测技术和算法、研究m6A RNA修饰的调控模式和机理，及其在干细胞、肿瘤等重大生理病理过程中的作用。实验室采用“干湿结合”的方式开展研究，通过算法开发、实验技术和组学技术开发从新的维度解析RNA修饰的模式，从新的角度提出前沿科学问题，并通过严谨的生化实验和组学分析深入阐明科学问题。

学术成果

      m6A RNA修饰是mRNA上最普遍的内源性修饰，在发育、免疫、肿瘤发生等多种生理或者病理过程中发挥重要作用。为了响应外界环境刺激并维持细胞内环境的稳态，m6A修饰展现出高度的选择性和时空特异性。然而，由于m6A功能广泛，整体干预m6A的策略在临床转化中面临困境，而选择性干预m6A的策略非常匮乏，主要原因是m6A的选择性调控机制尚不明确。

      实验室围绕“m6A如何选择性地标记不同的RNA特异性调控干细胞、肿瘤等重大生理病理过程”这一核心科学问题开展了一系列工作，主要成绩包括：

（1）针对m6A如何选择性地标记不同染色质区域的RNA，揭示了p300由于主要在H3K27ac的染色质上乙酰化METTL3，从而选择性地调控H3K27ac关联的染色质RNA的 m6A修饰，并介导PAK2激酶对肿瘤细胞铁死亡逃逸的促进作用。阐明了一种通过不同蛋白在细胞内亚空间上共同发生翻译后修饰介导m6A选择性调控的新型调控模式（Molecular Cell 2025a, 唯一通讯; Nature Chemical Biology，in press，共同通讯；Molecular Therapy 2024, 唯一通讯）。

（2）针对m6A如何选择性地标记相同基因的不同RNA异构体，通过建立在纳米孔直接RNA测序的单分子水平检测m6A修饰的深度学习模型，发现不同异构体在相同m6A位点也能形成差异的m6A修饰。在上皮-间质转化（EMT）中，激活的转录因子通过选择性促进同一基因中特定启动子驱动的RNA异构体的m6A修饰，实现对不同启动子来源RNA异构体的精细调控。揭示了一种全新的m6A修饰调控层次，开辟了异构体的表观转录组学新领域（Molecular Cell 2025b, 唯一通讯；Genome Biology2021, 唯一通讯）。
（3）针对m6A如何建立细胞特异性修饰模式，揭示大量细胞特异性表达的RNA结合蛋白（RBP）参与建立细胞特异性m6A模式。开发基于单碱基编辑的m6A位点功能筛选技术，发现在胚胎干细胞分化中不同m6A位点促进不同的分化方向。为理解m6A修饰的细胞特异性奠定了理论基础（Nature Communications 2022, 最后通讯；Nucleic Acids Research 2020, 唯一通讯; Genomics Proteomics and Bioinformatics 2023, 共同通讯）。

发表论文

 * 共同第一作者； # 通讯作者  本课题组成员或客座人员加粗显示

1. Huang X*, Zhang J*, Cun Y*, Ye M*, Ren Z*, Guo W, Ma X, Liu J, Luo W, Sun X, Shao J, Wu Z, Zhu X, Wang J# (2025a). Spatial control of m6A deposition on enhancer and promoter RNAs through co-acetylation of METTL3 and H3K27 on chromatin.Molecular Cell  (Online publication on 2025)（BioArt 报道）. （IF=14.5）
2. Guo W*, Ren Z*, Huang X*, Liu J, Shao J, Ma X, Wei C, Cun Y, He J, Zhang J, Wu Z, Guo Y, Zhang Z, Feng Z, He J, Wang J#(2025b). Single-molecule m6A detection empowered by endogenous labeling unveils complexities across RNA isoforms. Molecular Cell (Online publication on 2025) （BioArt 报道）. (IF=14.5）
3. Cun Y, Guo W, Ma B, Okuno Y, and Wang J# (2024). Decoding the specificity of m6A RNA methylation and its implication in cancer therapy. Molecular Therapy 32(8):2461-2469. （Invited review). （IF=12.4）
4. Yu P*, Zhou S*, Gao Y, Liang Y, Guo W, Wang DO, Ding S, Lin S#, Wang J#, Cun Y# (2022), Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues. Genomics, Proteomics & Bioinformatics S1672-0229(22)00092-4 (IF=11.5)
5. Sun X#, Wang DO, Wang J# (2022). Targeted manipulation of m6A RNA modification through CRISPR-Cas-based strategies. Methods 203:56-61（Invited review).
6. Cheng W*, Liu F*, Ren Z, Chen W, Chen Y, Liu T, Ma Y, Cao N #, Wang J # (2022), Parallel functional assessment of m6A sites in human endodermal differentiation with base editor screens, Nature Communications 13:478 (IF=17.7) (BioArt 报道)
7. Cun Y*, An S*, Zheng H*, Lan J, Chen W, Luo W, Yao C, Li X, Huang X, Sun X, Wu Z, Hu Y, Li Z, Zhang S, Wu G, Yang M, Tang M, Yu R, Liao X, Gao G, Zhao W, Wang J#, Li J# (2021), Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma. Genomics, Proteomics & Bioinformatics S1672-0229(21)00252-7. (IF=11.5) 
8. Tan L*, Cheng W *, Liu F, Wang DO, Wu L, Cao N, Wang J # (2021) Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes. Genome Biology, 22:180. (IF=17.9) （BioArt 报道）
9. Wang J (2021). Integrative analyses of transcriptome data reveal the mechanisms of post-transcriptional regulation. Briefings in Functional Genomics elab004 (Invited review)
10. Xia TL, Li X, Wang X, Zhu YJ, Zhang H, Cheng W, Chen ML, Ye Y, Li Y, Zhang A, Dai DL, Zhu QY, Yuan L, Zheng J, Huang H, Chen SQ, Xiao ZW, Wang HB, Roy G, Zhong Q, Lin D, Zeng YX, Wang J, Zhao B, Gewurz BE, Chen J, Zuo Z, and Zeng MS (2021). N(6)-methyladenosine-binding protein YTHDF1 suppresses EBV replication and promotes EBV RNA decay. EMBO Reports e50128.
11. Sun X*, Ren Z*, Cun Y, Zhao C, Huang X, Zhou J, Hu R, Su X, Ji L, Li P, Mak KLK, Gao F, Yang Y, Xu H, Ding J, Cao N, Li S, Zhang W, Lan P, Sun H, Wang J #, Yuan P # (2020). Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cells through modulating the formation of super-enhancers. Nucleic Acids Research 48(13):7182-7196. (IF=19.2)
12. An S*, Huang W*, Huang X*, Cun Y, Cheng W, Sun X, Ren Z, Chen Y, Chen W, Wang J#. (2020). Integrative network analysis identifies cell-specific trans regulators of m6A. Nucleic Acids Research  48(4):1715-1729. (IF=19.2) (BioArtMED 报道）
13. Shi J, Deng Y, Huang S, Huang C, Wang J, Xiang AP, and Yao C (2019). Suboptimal RNA-RNA interaction limits U1 snRNP inhibition of canonical mRNA 3' processing. RNA Biology 16(10): 1448-1460.
14. Li F, Yi Y, Miao Y, Long W, Long T, Chen S, Cheng W, Zou C, Zheng Y, Wu X, Ding J, Zhu K, Chen D, Xu Q, Wang J, Liu Q, Zhi F, Ren J, Cao Q, and Zhao W (2019). N(6)-Methyladenosine Modulates Nonsense-Mediated mRNA Decay in Human Glioblastoma. Cancer Research 79(22): 5785-5798.
15. Zhou C*, Molinie B*, Daneshvar K, Pondick JV, Wang J, Wittenberghe NV, Xing Y, Giallourakis CC#, Mullen AC#. (2017). Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs. Cell Reports, 20(9), 2262–2276.  (IF=9.4)
16. Wang J, Pan Y, Shen S, Lin L, Xing Y#. (2017). rMATS-DVR: rMATS discovery of Differential Variants in RNA. Bioinformatics 33(14), 2216-2217.  (IF=6.9)
17. Molinie B*, Wang J*, Lim KS, Hillebrand R, Lu ZX, Wittenberghe NV, Howard BD, Daneshvar K, Mullen AC, Dedon P, Xing Y#, Giallourakis CC#. (2016) m6A-LAIC-seq reveals the census and complexity of the m6A epitranscriptome. Nature Methods, 13(8):692-698. (IF=28.5)  
18. Batista PJ*, Molinie B*, Wang J*, Qu K, Zhang J, Li L, Bouley DM, Lujan E, Haddad B, Daneshvar K, Carter AC, Flynn RA, Zhou C, Lim KS, Dedon P, Wernig M, Mullen AC, Xing Y#, Giallourakis CC#, Chang HY# (2014) m6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15(6): 707–719. (IF=24.6)
19. Wang J*, Lu ZX*, Tokheim C, Miller SE, Xing Y#. (2015) Species-specific exon loss in human transcriptomes. Molecular Biology and Evolution 32(2): 481-94. (IF=16.2)
20. Lin L*#, Jiang P*, Park JW*, Wang J*, Lu ZX, Lam MPY, Ping P, Xing Y#. (2016) The contribution of Alu exons to the human proteome.Genome Biology 28;17(1):15  (IF=13.6) 
21. Wang J*, Ma MCJ*, Mennie AK*, Pettus JM, Xu Y, Lin L, Traxler MG, Jakoubek J, Atanur SS, Aitman TJ, Xing Y#, Kwitek AE#. (2015) Systems biology with high-throughput sequencing reveals genetic mechanisms underlying the metabolic syndrome in the Lyon hypertensive rat. Circulation: Cardiovascular Genetics 8(2):316-326.
22. Zhao Y*, Ji S*, Wang J*, Huang J#, Zheng P# (2014) mRNA-Seq and microRNA-Seq whole-transcriptome analyses of rhesus monkey embryonic stem cell neural differentiation revealed the potential regulators of rosette neural stem cells. DNA Research 21(5): 541–554. 
23. Li M*, Huang L*, Wang J*, Su B#, Luo X-J# (2016) No association between schizophrenia susceptibility variants and macroscopic structural brain volume variation in healthy subjects. Am J Med Genet B Neuropsychiatr Genet.  171B(2):160-8. 
24. Wang J*, Cao X*, Zhang Y, Su B#. (2012) Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates. BMC evolutionary biology 12(1): 144.
25. Wang J, Li Y, Su B#. (2008) A common SNP of MCPH1 is associated with cranial volume variation in Chinese population. Human Molecular Genetics 17(9): 1329-1335. 
26. Li M, Huang L, Li K, Huo Y, Chen C, Wang J, Liu J, Luo Z, Chen C, Dong Q, Yao YG, Su B, Luo XJ#. (2016) Adaptive evolution of interleukin-3 (IL3), a gene associated with brain volume variation in general human populations.  Human Genetics. 135(4):377-92. 
27. Luo X-J, Li M, Huang L, Nho K, Deng M, ... Wang J, … Su B#. (2012) The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors. PLoS ONE 7: e50375.
28. Kim J, Zhao K, Jiang P, Lu ZX, Wang J, Murray JC, Xing Y#. (2012) Transcriptome landscape of the human placenta. BMC genomics 13: 115. 
29. Niu AL, Wang YQ, Zhang H, Liao CH, Wang J, Zhang R, Che J, Su B#. (2011) Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function. BMC evolutionary biology 11: 298. 
30. Luo XJ, Diao HB, Wang J, Zhang H, Zhao ZM and Su B#. (2008) Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with schizophrenia in Han Chinese. J Med Genet, 45(12), 818-826.
31. Zhou L, Wang J, Yi Q, Wang YZ, Zhu YG and Zhang ZH#. (2007) Quantitative trait loci for seedling vigor in rice under field conditions. Field Crop Res 100: 294-301.