1989年，beat365正版唯一官网植物学专业，学士学位；
1995年，中山大学遗传学专业，硕士学位；
1999年，中国科学院微生物研究所微生物学，博士学位；
1999-2007年，美国科罗拉多大学博德分校生化系，博士后/访问学者；
2006-2008年，美国南加州大学分子与计算生物系，访问学者；
2008年至今，beat365正版唯一官网，教授。
B.S. 1989, Nanjing University, Botany;
M.S. 1995, Sun Yat-Sen University, Genetics;
Ph.D. 1999, Institute of Microbiology, Chinese Academy of Sciences, Microbiology;
Postdoctoral Follow/Visiting Scholars, University of Colorado at Boulder, 1999-2007;
Senior Research Associate, University of Southern California, 2006-2008;
Professor, School of Life Sciences, Xiamen University, 2008 to Present.

        课题组以结构生物学为主要的研究手段，揭示细胞的信号转导、物质运输、蛋白质翻译后修饰、以及微生物与宿主相互作用等生理活动的分子机制。 在真核细胞中，蛋白质的乙酰化修饰通常发生在N末端和赖氨酸侧链上，是细胞转录的表观遗传调控，以及蛋白质功能，稳定性和细胞内定位调控的重要手段。N末端乙酰转移酶(NAT)负责蛋白质N末端乙酰化修饰(图1)。组蛋白乙酰转移酶(HAT)和组蛋白去乙酰化酶(HDAC)负责赖氨酸侧链的乙酰化修饰。我们也研究蛋白质的其它修饰，如tau蛋白的磷酸化修饰在胞内物质转运以及在神经退行性疾病中的作用机制等。微生物还通过分泌型效应因子（Effector）的方法调控胞内的物质运输，如军团菌利用其LegA15的GTPase活性操控宿主细胞的物质转运活动(图2)。
        在原核细胞中，组氨酸激酶(Sensor histidine kinase, HK)负责刺激依赖的组氨酸磷酸化，并将信号传导至相连的调节蛋白(Response regulator, RR)，以调控各种生物学过程。这一调控系统被称为双组分系统(Two-component system, TCS)。基因表达的转录调控是TCS的一个主要功能 。一些常见的革兰氏阳性细菌，如金黄色葡萄球菌，肺炎链球菌等，引起脑膜炎、皮肤炎、鼻竇炎、肺炎等感染性疾病，更容易产生抗生素的耐药性。WalRK, 也叫VicRK或YycFG是这些细菌中关键的TCS。课题组解析了完整的胞内WalK的晶体结构(图3)，正试图解析带有细胞外感应结构域的全长WalRK复合体结构，以探索HAMP和PAS等结构域介导的信号转导和激酶活性调控机制，并积极研发靶向特异的新型抗生素。我们对革兰氏阴性细菌中的TCS也感兴趣，比如钾离子感应系统KdpDE（图4），并试图解析信号感应特异性KdpD的冷冻电镜结构。
My lab is interested in understanding molecular mechanisms of several key biological processes, including transmembrane signal transduction, intracellular trafficking, protein post-translational modification (PTM), and microbe-host interactions. Protein acetylation, one of important PTMs, regulates protein function, stability and cellular localizations in eukaryotic cells. Proteins can be acetylated at the amine group of peptidic N-terminus and lysine side chain. A group of proteins called N-terminal acetyltransferases (NAT), such as NatB (Fig. 1), acetylate protein N-terminus. The lysine acetylation as one of important means for epigenetic regulations in transcription is carried out reversibly by histone acetyltransferases (HAT) and histone deacetylases (HDAC), which often form high-order regulatory complexes. It is well known that protein PTMs are often combined with other PTM, such as phosphorylation by a variety of protein kinases in broader biological processes. The tau phosphorylation, for example, is important for its spreading and therefore in neurodegenerative diseases. In addition, intracellular microbial pathogens are able to secret effector proteins to regulate intracellular trafficking. We found that LegA15 as GTPase of Legionella hijacks a general vescular factor p115 of the host cells (Fig. 2).
In prokaryotic cells, two-component system (TCS), including histidine kinase (SK) and response regulator (RR), is responsible for a diverse of biological processes, one of which is stimuli induced transcription. Our lab uses WalRK, also called VicRK or YycFG, an essential TCS in several Gram-positive bacteria as a model system to understand how intra/extracellular signals regulate the gene transcription for bacterial survival under stress environments. With crystal or CroEM structures (Fig. 3), we hope to develop leading compounds for new antibiotics that may overcome the rapidly progressing antibiotic resistance in these pathogenic bacteria. We are also interested in several important TCSs in Gram-negative bacteria. As an example, we recently determined a complex structure of potassium sensing system KdpDE, revealing a unique model for specific recognition and signal transduction of a TCS (Fig. 4).

代表性论文(^# co-first author, ^* Corresponding author):

1.Chen, TT, Lin, Y, Zhang, S, Liu, S, Song, L, Zhong, W, Luo, ZQ and Han, A (2022). Atypical Legionella GTPase effector hijacks host vesicular transport factor p115 to regulate host lipid droplet.Science Advances 8, eadd7945
2.Kong, L, Su, M, Sang, J, Huang, S, Wang, M, Cai, Y, Xie, M, Wu, J, Wang, S, Foster, SJ, Zhang, J, and Han, A (2022). The W-Acidic Motif of Histidine Kinase WalK Is Required for Signaling and Transcriptional Regulation in Streptococcus mutans. Frontier in Microbiology 13, 820089
3.Salamaga, B, Kong, L, Pasquina-Lemonche, L, Lafage, L, Muhlen, M, Gibson, J, Grybchuk, D, Tooke, A, Panchal, V, Culp, E, Tatham, E, O'Kane, M, Catley, T, Renshaw, S, Wright, G, Plevka, P, Bullough, P, Han, A*, Hobbs, J* and Foster, S*. (2021). Demonstration of the rol e of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics. PNAS 118 (44): e2106022118
4.Liu, W, Li, X, Qi, H, Wu, Y, Qu, J, Yin, Z, Gao, X, Han, A* and Shuai, J* (2021). Biphasic regulation of transcriptional surge generated by the gene feedback loop in a two-component system, Bioinformatics 37 (17): 2682-2690
5.Xie, M, Wu, M, Han, A (2020). Structural insights into the signal transduction mechanism of the K+-sensing two-component system KdpDE. Science Signaling 13: eaaz2970.
6.Cai, Y, Su M, Ahmad, A, Hu, X, Sang, J, Kong, L, Chen, X, Wang, C, Shuai, J, Han, A (2017). Conformational dynamics of the essential sensor histidine kinase WalK. Acta Crystallography D Structure Biololgy 73 (Pt 10):793-803.
7.Hong, H, Cai, Y, Zhang, S, Ding, H, Wang, H and Han, A (2017). “Molecular basis of substrate specific acetylation by N-terminal acetyltransferase NatB.” Structure 25 (4): 641-9.
8.Shi, S, Liu, K., Chen, Y, Zhang, S, Lin, J, Gong, C, Jin, Q, Yang, X, Chen, R, Ji, Z and Han, A (2016). “Competitive inhibition of lysine acetyltransferase 2B by a small motif of the adenoviral oncoprotein E1A.” Journal of Biological Chemistry 291 (27): 14363-72.
9.Ahmad, A, Cai, Y, Chen, X, Shuai, J and Han, A (2015). "Conformational dynamics of response regulator regx3 from Mycobacterium tuberculosis." PLoS One 10 (7): e0133389.
10.Wang, C, Sang, J, Wang, J, Su, M, Downey, JS, Wu, Q, Wang, S, Cai, Y, Xu, X, Wu, J, Senadheera, DB, Cvitkovitch, DG, Chen, L, Goodman, SD and Han, A (2013). "Mechanistic insights revealed by the crystal structure of a histidine kinase with signal transducer and sensor domains." PLoS Biology 11 (2): e1001493.
11.Jayathilaka, N, Han, A, Gaffney, KJ, Dey, R, Jarusiewicz, JA, Noridomi, K, Philips, MA, Lei, X, He, J, Ye, J, Gao, T, Petasis, NA and Chen, L (2012). "Inhibition of the function of class IIa HDACs by blocking their interaction with Mef2." Nucleic Acids Research 40(12): 5378-5388.
12.Mao, Y, Lin, J, Zhou, A, Ji, K, Downey, JS, Chen, R and Han, A (2011). "Quikgene: A gene synthesis method integrated with ligation-free cloning." Analytical Biochemistry 415 (1): 21-26.
13.He, J, Ye, J, Cai, Y, Riquelme, C, Liu, JO, Liu, X, Han, A and Chen, L (2011). "Structure of p300 bound to Mef2 on DNA reveals a mechanism of enhanceosome assembly." Nucleic Acids Research 39 (10): 4464-4474.
14.Guo, L, Han, A, Bates, DL, Cao, J and Chen, L (2007). "Crystal structure of a conserved n-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains." Proceedings of the National Academy of Science USA 104 (11): 4297-4302.
15.Han, A, He, J, Wu, Y, Liu, JO and Chen, L (2005). "Mechanism of recruitment of class ii histone deacetylases by myocyte enhancer factor-2." Journal of Molecular Biology 345 (1): 91-102.
16.Han, A, Pan, F, Stroud, JC, Youn, HD, Liu, JO and Chen, L (2003). "Sequence-specific recruitment of transcriptional co-repressor cabin1 by myocyte enhancer factor-2." Nature 422 (6933): 730-734.

荣誉、奖励及参加学术团体的情况: