先后主持國家自然科學(xué)基金6項(xiàng)、973項(xiàng)目課題1項(xiàng)。在國際期刊發(fā)表SCI論文160余篇,SCI他引3000余次。1篇論文被Thomson Scientific評為Top 1%論文,1篇論文入選Faculty of 1000 Biology,1篇論文入選ScienceDirect Top 25 熱點(diǎn)論文。取得的主要科研進(jìn)展如下:
1.蛋白質(zhì)起源:基于小分子的保守性,使用小分子作為分子化石追溯了蛋白質(zhì)的起源歷程,提出“蛋白質(zhì)起源的小分子誘導(dǎo)/選擇模型”,得到初步實(shí)驗(yàn)結(jié)果的支持(Ji et al. 2007)。
2.代謝進(jìn)化:根據(jù)代謝物分子化石的地質(zhì)年代,標(biāo)定了蛋白質(zhì)結(jié)構(gòu)的分子鐘,追溯了有氧代謝起源等重要進(jìn)化事件,深化了對生物化學(xué)與地球化學(xué)共進(jìn)化的認(rèn)識(shí)(Wang et al. 2011;Kim et al. 2012);用化學(xué)信息學(xué)方法探討了代謝產(chǎn)物在化學(xué)空間中的進(jìn)化規(guī)律,揭示了代謝網(wǎng)絡(luò)組織與進(jìn)化的化學(xué)基礎(chǔ),解釋了氧氣促進(jìn)代謝進(jìn)化的分子機(jī)制(Zhu et al. 2011;Jiang et al. 2012)。
3.系統(tǒng)調(diào)控與進(jìn)化:用藥物作為分子探針,結(jié)合其作用靶標(biāo)信息,鑒別出12個(gè)轉(zhuǎn)錄因子與基因模塊之間的調(diào)控網(wǎng)絡(luò)(Xiong et al. 2014);將3D基因組學(xué)引入進(jìn)化領(lǐng)域,從染色質(zhì)空間組織的角度探討了重復(fù)基因維持劑量平衡的機(jī)制(Xie et al. 2016)。
4.藥物發(fā)現(xiàn):將進(jìn)化生物學(xué)的概念和方法引入藥物發(fā)現(xiàn)領(lǐng)域,揭示了藥物靶標(biāo)的進(jìn)化特征和天然產(chǎn)物多靶標(biāo)作用的進(jìn)化起源(Ji et al. 2009;Zhang et al. 2010);從靶標(biāo)遺傳學(xué)角度揭示了藥物活性的決定機(jī)制,建立了藥物活性預(yù)測的系統(tǒng)化學(xué)遺傳學(xué)方法(Wang and Zhang 2013)。
代表性論文:
1. Xie T., Yang Q.-Y., Wang X.-T., McLysaght A.*,Zhang H.-Y.* (2016) Spatial colocalization of human ohnolog pairs acts to maintain dosage-balance. Mol. Biol. Evol. 33: 2368-2375. (*corresponding authors)
2. Xiong M., Li B., Zhu Q., Wang Y.-X.,Zhang H.-Y.* (2014) Identification of transcription factors for drug-associated gene modules and biomedical implications. Bioinformatics 30: 305-309. (*corresponding author)
3. Peng C.*, Fu L.-Y., Dong P.-F., Deng Z.-L., Li J.-X., Wang X.-T.,Zhang H.-Y.* (2013) The sequencing bias relaxed characteristics of Hi-C derived data and implications for chromatin 3D modeling. Nucleic Acids Res. 41: e183. (*corresponding authors)
4. Wang Z.-Y.,Zhang H.-Y.* (2013) Rational drug repositioning by medical genetics. Nat. Biotechnol. 31: 1080-1082. (*corresponding author)
5. Jiang Y.-Y., Kong D.-X., Qin T., Li X., Caetano-Anollés G.,Zhang H.-Y.* (2012) The impact of oxygen on metabolic evolution: a chemoinformatic investigation. PLoS Comput. Biol. 8: e1002426. (*corresponding author)
6. Kim K. M., Qin T., Jiang Y.-Y., Chen L.-L., Xiong M., Caetano-Anollés D.,Zhang H.-Y.*, Caetano-Anollés G.* (2012) Protein domain structure uncovers the origin of aerobic metabolism and the rise of planetary oxygen. Structure 20: 67-76. (*corresponding authors) (Preview: Saito, M. A. Structure 2012, 20: 1-2) (Featured by Science News: http://news.sciencemag.org/sciencenow/2012/01/the-first-oxygen-users.html)
7. Wang M., Jiang Y.-Y., Kim K. M., Qu G., Ji H.-F., Mittenthal J. E.,Zhang H.-Y.*, Caetano-Anollés G.* (2011) A universal molecular clock of protein folds and its power in tracing the early history of aerobic metabolism and planet oxygenation. Mol. Biol. Evol. 28: 567-582. (*corresponding authors)
8. Zhu Q., Qin T., Jiang Y.-Y., Ji C., Kong D.-X., Ma B.-G.,Zhang H.-Y.* (2011) Chemical basis of metabolic network organization. PLoS Comput. Biol. 7: e1002214. (*corresponding author)
9.Zhang H.-Y.*, Chen L.-L., Li, X.-J., Zhang J. (2010) Evolutionary inspirations for drug discovery. Trends Pharmacol. Sci. 31: 443-448. (*corresponding author)
10. Ji H.-F., Li X.-J.,Zhang H.-Y.* (2009) Natural products and drug discovery. EMBO Rep. 10: 194-200. (*corresponding author)
11. Ji H.-F., Kong D.-X., Shen L., Chen L.-L., Ma B.-G.,Zhang H.-Y.* (2007) Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery. Genome Biol. 8: R176. (*corresponding author)
12.Zhang H.-Y.*, Sun Y.-M., Wang X.-L. (2003) Substituent effects on O-H bond dissociation enthalpies and ionization potentials of catechols: a DFT study and its implications in rational design of phenolic antioxidants and elucidation of structure-activity relationships for flavonoid antioxidants. Chem. Eur. J. 9: 502-508. (*corresponding author) (ESI Top 1% paper)