Biography
Prof. Hailong An
Prof. Hailong An
Hebei University of Technology, China
Title: Identification of the calcium-dependent gating mechanism and drug discovery targeting CaCCs
Abstract: 
 Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Transmembrane protein 16A (TMEM16A) has been confirmed as the molecular counterpart of CaCCs which greatly pushes the molecular insights of CaCCs forward. However, the detailed mechanism of Ca2+ binding and activating the channel is still obscure. To identify the calcium binding site, the authors presented a computational approach which combined the fragment homology modeling with molecular dynamics simulation. Our data show that the first intracellular loop serves as a Ca2+ binding site including D439, E444 and E447. The experimental results indicate that a novel residue, E447, plays key role in Ca2+ binding. Compared with WT TMEM16A, E447Y produces a 30-fold increase in EC50 of Ca2+ activation and leads to a 100-fold increase in Ca2+ concentrations that is needed to fully activate the channel. 
It is well established that TMEM16A is a drug target in many diseases, including cystic fibrosis, hypertension, asthma, and various tumors. Therefore, identifying potent and specific modulators of the TMEM16A channel is crucial. Here, the authors identified two modulators from the traditional Chinese medicine, an activator, Ginsenoside Rb1 (GRb1) which can directly activate the channel, increase the amplitude and frequency of contractions in an isolated guinea pig ileum assay in vivo and may serve as a lead compound for the development of novel drugs for the treatment of diseases caused by TMEM16A dysfunction, inhibitors, matrine and arctigenin which can dramatically inhibit the growth of lung adenocarcinoma tumors in xenografted mice, and may function as an anti-lung adenocarcinoma drug targeting at TMEM16 channels.
Biography: 
Dr. Hailong An received his Ph.D. degree in Biophysics in Hebei University of Technology in 2005. After that, he was appointed to the faculty in Institute of Biophysics, Hebei University of Technology. Awarded by China Scholarship Council, he has been to Virginia Commonwealth University and Washington University in Saint Louis as a visiting scholar.
Dr. Hailong An focuses on understanding the relationship of structure and function and drug discovery targeting voltage gated potassium channel, Kv10.1 and calcium activated chloride channel, CaCCs, dysfunction of which contribute to a variety of human diseases and may serve as novel drug targets in clinic treatment. Dr. An has published more than 50 articles in journals including, Journal of Biological Chemistry, Biophysical Journal, Pharmacological Research, British Journal of Pharmacology, Journal of Cellular Physiological etc. and has achieved more than 320 citations, H-index=9. He has been funded by more than 20 research projects from the National Natural Science Foundation of China or provincial items.