先后主持國家自然科學基金6項、973項目課題1項。在國際期刊發表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 熱點論文。取得的主要科研進展如下:
1.蛋白質起源: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的起源歷程,提出“蛋白質起源的小分子誘導/選擇模型”,得到初步實驗結果的支持(Ji et al. 2007)。
2.代謝進化:根據代謝物分子化石的地質年代,標定了蛋白質結構的分子鐘,追溯了有氧代謝起源等重要進化事件,深化了對生物化學與地球化學共進化的認識(Wang et al. 2011;Kim et al. 2012);用化學信息學方法探討了代謝產物在化學空間中的進化規律,揭示了代謝網絡組織與進化的化學基礎,解釋了氧氣促進代謝進化的分子機制(Zhu et al. 2011;Jiang et al. 2012)。
3.系統調控與進化:用藥物作為分子探針,結合其作用靶標信息,鑒別出12個轉錄因子與基因模塊之間的調控網絡(Xiong et al. 2014);將3D基因組學引入進化領域,從染色質空間組織的角度探討了重復基因維持劑量平衡的機制(Xie et al. 2016)。
4.藥物發現:將進化生物學的概念和方法引入藥物發現領域,揭示了藥物靶標的進化特征和天然產物多靶標作用的進化起源(Ji et al. 2009;Zhang et al. 2010);從靶標遺傳學角度揭示了藥物活性的決定機制,建立了藥物活性預測的系統化學遺傳學方法(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)