教育经历

2014-2020  武汉大学，博士

2014-2014  中科院上海生命科学研究院生物化学与细胞生物学研究所，科研实习

2009-2013  信阳师范学院，学士

工作经历

2021/01-至今  武汉大学生命科学学院

社会兼职

中国生物物理学会代谢生物学分会青年委员

奖励荣誉

2020年“中国生命科学十大进展”

2021年“武汉大学研究生学术创新奖”特等奖（研究生学术创新校长奖）

2021年“武汉大学研究生学术之星特别奖”

承担项目

1）国家自然科学基金委重大研究计划培育项目（2022-2024） 主持

2）国家自然科学基金委面上项目（2023-2026） 主持

3）科技部国家重点研发计划“青年科学家项目”（2022-2027） 项目骨干

4）武汉大学自主科研青年教师资助项目（2022-2023） 主持

研究概述

　　胆固醇是生命活动必需的脂类物质，能够调节细胞膜功能，作为胆汁酸和类固醇激素的前体，并共价修Hedgehog及Smoothened蛋白。人体所需胆固醇中，约1/3从食物中摄取，2/3依靠内源合成，其中肝脏是胆固醇合成最主要器官。高水平的胆固醇和其他脂质是心血管疾病、非酒精性脂肪肝、肥胖和糖尿病等的主要危险因素。在哺乳动物中，喂食后胆固醇的生物合成增加，并且在禁食条件下受到抑制。研究发现进食后胰岛素和葡萄糖信号通路激活mTORC1，后者磷酸化USP20，促进HMGCR去泛素化而提高其稳定性，进而增加胆固醇合成。抑制该通路导致机体能量损耗，以产热形式释放，抵抗食物诱导的体重增加，改善血脂、胰岛素敏感性等代谢综合征表型，为该类疾病的治疗提供了新的重要思路（Nature，2020，588：479-484）。发现IDOL基因G51S 突变增强LDLR 蛋白泛素化降解，导致血液LDL-C水平升高（ATVB, 2019, 39: 2468-2479）。

Cholesterol is an essential lipid. It regulates cell membrane function, acts as a precursor of bile acids and steroid hormones, and covalently modifies the Hedgehog and Smoothened proteins. However, high levels of cholesterol and other lipids are major risk factors for cardiovascular disease, non-alcoholic fatty liver, obesity and diabetes. In mammals, cholesterol biosynthesis increases after feeding and is inhibited in fasting condition. I am interested in understanding the mechanisms of cholesterol metabolism in different nutrient conditions. Our studies have found that insulin and glucose signaling pathways activate mTORC1 after feeding. The mTORC1 then phosphorylates USP20, promotes HMGCR deubiquitination and improves its stability, thereby increasing cholesterol synthesis. Inhibition of this pathway increases energy expenditure, decreases lipid levels and improves insulin sensitivity (Nature,2020,588:479-484). In addition, we found that the IDOL(G51S) mutation causes high blood cholesterol by promoting the degradation of low-density lipoprotein receptor（ATVB, 2019, 39: 2468-2479)

代表性学术论文/ Selected Publications （#: co-first author）

1. Xiao-Yi Lu^#, Xiong-Jie Shi^#, Ao Hu^#, Ju-Qiong Wang^#, YiDing,Wei Jiang, Ming Sun, Xiaolu Zhao, Jie Luo, Wei Qi, Bao-Liang Song*. Feeding induces cholesterol biosynthesis via the mTORC1–USP20–HMGCR axis, Nature, 588(7838): 479-484, 2020

2. Dilare Adi^#, Xiao-Yi Lu^#, Zhen-Yan Fu^#, Jian Wei, Gulinaer Baituola, Ya-Jie Meng, Yu-Xia Zhou, Ao Hu, Jin-Kai Wang, Xiang-Feng Lu, Yan Wang, Bao-Liang Song, Yi-Tong Ma, Jie Luo. IDOL G51S Variant Is Associated With High Blood Cholesterol and Increases Low-Density Lipoprotein Receptor Degradation. Arterioscler Thromb Vasc Biol, 39: 2468-2479. 2019

3. Ju-Qiong Wang^#, Liang-Liang Li, Ao Hu, Gang Deng, Jian Wei, Yun-Feng Li, Yuan-Bin Liu, Xiao-Yi Lu, Zhi-Ping Qiu, Xiong-Jie Shi, Xiaolu Zhao, Jie Luo & Bao-Liang Song*. Inhibition of ASGR1 decreases lipid levels by promoting cholesterol excretion, Nature, 608: 413–420. 2022.

4. Jin-Kai Wang^#, Yang Li, Xiao-Lu Zhao, Yuan-Bin Liu, Jing Tan, Yu-Ying Xing, Dilare Adi, Yong-Tao Wang, Zhen-Yan Fu, Yi-Tong Ma, Song-Mei Liu, Yong Liu, Yan Wang, Xiong-Jie Shi, Xiao-Yi Lu, Bao-Liang Song, Jie Luo*Ablation of Plasma Prekallikrein Decreases LDL Cholesterol by Stabilizing LDL Receptor and Protects Against Atherosclerosis. Circulation, 145(9):675-687, 2022.