Biography

2023.09-now    PI, Taikang Center for Life and Medical Sciences of Wuhan University

2023.02-now    Professor, School of Pharmaceutical Sciences, Wuhan University

2019.09-2023.01  Postdoc, Department of Molecular Biology, Princeton University

2014.09-2019.06  Ph.D. School of Pharmaceutical Sciences, Tsinghua University

2010.09-2014.06  B.S. School of Pharmaceutical Sciences, Shandong University

Research

Ion channels, widely distributed throughout the human body, form the foundation of bioelectric activities and play crucial roles in fundamental life processes such as heartbeats, muscle contractions, and neurotransmitter release. Abnormalities in ion channel will lead to severe congenital or acquired diseases affecting vital organs including muscles, heart, and kidneys. Notably, ion channels represent an important class of drug targets. Drugs targeting ion channels have proven effective in treating common clinical conditions like hypertension, arrhythmias, epilepsy, chronic pain, and parasitic infections.

Our research team employs interdisciplinary methods, encompassing structural biology, cell biology, and medicinal chemistry, to unravel the molecular basis of channelopathies and explore diverse modes of action for drugs targeting ion channels. Our ultimate objective is to develop novel, effective, and safe drug candidates for treating severe channelopathies.

Our specific research directions are listed below.

1. Elucidating the pharmacological effects and resistance mechanisms of commonly used clinical ion channel drugs. We will apply structure-based drug discovery method to optimize the activity and selectivity of the reported drugs, developing more effective and safer ion channel drugs.

2. Investigating the dynamic regulation of ion channels using structural analysis, single-molecule fluorescence, and molecular dynamics simulations, which will help to uncover the potential specific allosteric sites in proteins and develop highly selective ion channel allosteric modulators.

3. Exploring novel regulatory mechanisms of ion channels, identifying unknown regulatory proteins and developing regulators targeting protein-protein interactions.

Developing innovative technologies and methods for high-throughput screening of ion channel drugs.

Representative  Publications

1. Xia Yao^#, Shuai Gao^#*, Jixin Wang, Zhangqiang Li, Jian Huang, Yan Wang, Zhifei Wang, Jiaofeng Chen, Xiao Fan, Weipeng Wang, Xueqin Jin, Xiaojing Pan, Yong Yu, Armando Lagrutta, and Nieng Yan^*, Structural basis for the severe adverse interaction of sofosbuvir and amiodarone on L-type Cav channels. Cell, 185，4801-4810 (2022)

2. Shuai Gao^#*, Xia Yao^#, Jiaofeng Chen^#, Gaoxingyu Huang, Xiao Fan, Lingfeng Xue, Zhangqiang Li, Tong Wu, Yupeng Zheng, Jian Huang, Xueqin Jin, Yan Wang, Zhifei Wang, Yong Yu, Lei Liu, Xiaojing Pan, Chen Song^*, and Nieng Yan^*, Structural basis for human Cav1.2 inhibition by multiple drugs and the neurotoxin calciseptine. Cell, In press

3. Shuai Gao^#, Xia Yao^#, Nieng Yan^*, Structure of human Cav2.2 channel blocked by the painkiller ziconotide. Nature, 596, 143-147 (2021)

4. Xia Yao, Yan Wang, Zhifei Wang, Xiao Fan, Di Wu, Jian Huang, Alexander Mueller, Sarah Gao, Miaohui Hu, Carol V. Robinson, Yong Yu, Shuai Gao^*, Nieng Yan^*, Structures of the R-type human Cav2.3 channel reveal conformational crosstalk of the intracellular segments. Nature Communications, 13, 7358 (2022)

5. Xia Yao^#*, Shuai Gao^#, Nieng Yan^*, Structural basis for pore blockade of human voltage-gated calcium channel Cav1.3 by motion sickness drug cinnarizine. Cell Research, 32, 946-948 (2022)

6. Xia Yao^#, Xiao Fan^#*, Nieng Yan^*, Cryo-EM analysis of a membrane protein embedded in the liposome. PNAS, 117, 18497-18503 (2020)

7. Xia Yao^#, Xiuyun Sun^#, Shuyu. Jin, Ling Yang, Hongjiang Xu, Yu Rao^*, Discovery of 4-aminoquinoline-3- carboxamide derivatives as potent reversible bruton’s tyrosine kinase inhibitors for the treatment of rheumatoid arthritis. Journal of Medicinal Chemistry, 62, 6561–6574 (2019)

8. Xiuyun Sun^#, Jun Wang^#, Xia Yao^#, Wen Zheng, Yang Mao, Tianlong Lan, Liguo Wang, Yonghui Sun, Xinyi Zhang, Qiuye Zhao, Jiangguo Zhao, Ruiping, Xiao, Xiuqin Zhang^*, Guangju Ji^*, Yu Rao^*, A chemical approach for global protein knockdown from mice to non-human primates. Cell Discovery, 5:10 (2019)