Cuishuang

1、Educational Experience

2017/09-2012/06, School of Pharmacy, China Pharmaceutical University, Ph.D

2014/09-2017/06, School of Pharmacy, China Pharmaceutical University, Master

2010/09-2014/06, College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Bachelor

2、Working Experience

2021/07-present, School of Pharmacy, China Pharmaceutical University, Post-doctoral

(1) Shuang Cui; Huijian Hu; An Chen; Ming Cui; Xiaojie Pan; Pengfei Zhang; Guangji Wang; Hong Wang; Haiping Hao; SIRT1 activation synergizes with FXR agonism in hepatoprotection via governing nucleocytoplasmic shuttling and degradation of FXR, Acta Pharmaceutica Sinica B, 2023, 13(2): 559-576. (IF: 14.903)

(2) Shuang Cui; Xiaojie Pan; Chaoliang Ge; Yitong Guo; Pengfei Zhang; Tingting Yan; Jiyu Zhou; Qingxian He; Longhao Cheng; Guangji Wang; Haiping Hao; Hong Wang; Silybin alleviates hepatic lipid accumulation in methionine-choline deficient diet-induced nonalcoholic fatty liver disease in mice via peroxisome proliferator-activated receptor a, Chinese Journal of Natural Medicines, 2021, 19(6): 401-411. (IF: 3.887)

      (3) Jiyu Zhou; Shuang Cui; Qingxian He; Yitong Guo; Xiaojie Pan; Pengfei Zhang; Ningning Huang; Chaoliang Ge; Guangji Wang; Frank J. Gonzalez; Hong Wang; Haiping Hao; SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis, Nature Communications, 2020,11(1): 240. (IF: 17.694)

1. Nuclear receptor dynamic regulation process and targeted drugs in liver diseases

2. Therapeutic agents and strategies related to nonalcoholic fatty liver disease

3. Metabolic regulation and drug targets and confirmation

1、Research Projects

National Natural Science Foundation of China, Youth Science Fund Project, 82204512, Molecular target and mechanism of hepatotoxicity induced by FXR agonists off-target effects in liver injury, 2023-01-01 - 2025-12-31, in research, host.

2、Academic Awards

3、Representative Research Achievements

Farnesoid X receptor (FXR) is widely accepted as a promising target for various liver diseases; however, panels of ligands in drug development show limited clinical benefits, without a clear mechanism. We reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury, which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases. Upon inflammatory and apoptotic stimulation, enhanced FXR acetylation at K217, closed to the nuclear location signal, blocks its recognition by importin KPNA3, thereby preventing its nuclear import. Concomitantly, reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1, and thereby facilitating FXR export to the cytosol. Acetylation governs nucleocytoplasmic shuttling of FXR, resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP. SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation. More importantly, SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries. In conclusion, these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.