申请人聚焦免疫信号通路JNK/p38参与炎症消退的调控机制进行研究。1)发现RACK1在炎性微环境中过量表达、介导MAP2K-JNK/p38-BAD活性紊乱、阻断炎症消退的新分子机制；2)揭示cAMP和neddylation分别通过不同分子途径负向调节JNK/p38；3)发现生理浓度的RACK1在体内不影响JNK/p38活化，通过激活自噬促进炎症消退。系列研究为炎症消退障碍提供新理论、为特异阻断JNK/38病理效应提供靶点；应邀在Trends Pharmacol Sci上发表综述，提出诱导炎症消退的新策略；成功制备特异阻断p38病理效应的新型抑制因子，进入临床前研究。共发表SCI文章46篇，累积影响因子255，他引557次。近5年作为唯一或合作通讯作者在Cell Rep,Hepatology,Oncogene,MBC,Mol Ther等杂志发表SCI论文16篇。申请发明专利5项，获批2项。

Dr. Zhang focuses on understanding the regulation of JNK/p38 immune signaling pathways in inflammation resolution. The major academic achievements in recent years include: 1) Disclosure of the cell-intrinsic defects which lead to the persistent activation of JNK/p38 in chronic inflammation. For the first time, Dr. Zhang has reported that adaptor RACK1, which exhibits elevated expression in chronic inflammation, could engage in a direct interaction with MAP2Ks and thereby enhancing their activity. Meanwhile, Dr. Zhang has revealed the pro-survival role of JNK and the substrate, the isoform, and the subcellular localization involved. These findings promote a new starting point for our continuous efforts to understand the pathogenesis underlying the failure of resolution. 2) Identification of the mechanisms by which cAMP and neddylation inhibit the activation of JNK and/or p38. The findings emphasize the importance of protein-protein interaction in the regulation of JNK/p38 activity and thereby propose a novel strategy for intervention. 3) Identification of a novel mechanism underlying autophagy induction and a pivotal role for RACK1 in postnatal mammalian physiology. As the activation of JNK/p38 during liver regeneration and fasting is not affected by RACK1 deficiency, it is relatively safe to target RACK1/MAP2K interaction to inactivate JNK/p38 to alleviate inflammation. Dr. Zhang’s invited review published in the prestigious journal "Trends Pharmacol Sci" has proposed novel strategies to induce inflammation resolution. Furthermore, Dr. Zhang has designed and characterized the first "non-ATP-competitive" p38 inhibitor. The patented inhibitor blocks TAB1/p38 interaction with selectivity and induces inflammation resolution in vivo. In the past five years, she has published 16 articles in SCI journals including Cell Rep, Hepatology, Oncogene, Mol Biol Cell, Mol Ther, Cell Death Dis, Sci Rep, and Oncotarget as the last author.