"If biopharmaceutical industry is still in the ' Stone Age ', I am willing to be a 'drilling wood to make fire'." researcher at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences said.
explores the underlying logic of life science and works hard to make original innovative drugs, which is exactly what he has been doing.
[He made a decision that others couldn't understand and went to Shanghai to work for half a year every year]
There have been two important turning points on Xu Huaqiang's scientific research path. The first time was from enterprises to academic circles. The second time was from the United States to China.
16 was admitted to Tsinghua University from Fujian at the age of 16. Xu Huaqiang originally wanted to learn high-energy physics , but he accidentally entered the nuclear reactor major. He clearly realized that what he liked was scientific research, not engineering technology. He taught himself biophysics , and in , he was admitted to the master's degree in the Department of Biology at Tsinghua University with the first place in 1985.
After graduating from the Department of Plant Genetics at Duke University in the United States, Xu Huaqiang wanted to combine his favorite physics with genetics , so he applied to Professor Carl Pabo of of of at MIT for postdoctoral research. "The first letter, he ignored me, I wrote the second and third letters, and sent my paper to him, and he finally agreed."
Xu Huaqiang, who completed postdoctoral research, went to Glaxo SKP, the world's top five pharmaceutical company. He already had a wife and children at that time, which was a realistic consideration. In just six years, he was promoted to senior fellow. At this moment, he made a decision that outsiders seemed incredible, and came to Wen'ander Institute in , Michigan to build his own laboratory. The reason is actually very simple. There is little freedom to explore in enterprises, while Xu Huaqiang is still persistent in wanting to study scientific problems.
"China is developing very fast, you should go and see it with your own eyes." There is a student from Shanghai in Xu Huaqiang's laboratory, who has been saying this. Xu Huaqiang, who only retains the memory of green trains in Shanghai, really came to Shanghai and felt that it was "very different". By chance, in 2008, Jiang Hualiang, who was then the deputy director of Shanghai Institute of Pharmaceuticals, found Xu Huaqiang, hoping that he would help establish a drug target center and improve the R&D capabilities of original innovative drugs. At that time, Xu Huaqiang's laboratory in the United States was on the rise, and he made another decision that others could not understand. He went to Shanghai to work for half a year every year. The Shanghai Institute of Pharmaceuticals and Wen'ande Institute signed an agreement to jointly build a joint laboratory.
[Update difficulties with "breakthrough" as the keyword]
No matter how the road of life goes around, in July 2010, 46-year-old Xu Huaqiang embarked on a new journey in Shanghai. For him, it is a 12-year breakthrough with the keyword "breakthrough". For the research and development of original innovative drugs in Shanghai, the research level of the structure and function of drug targets has been improved.
Xu Huaqiang won the Hans Neurath Award from the International Protein Society. Shanghai Institute of Pharmaceuticals provides
fragrance of flowers makes people happy, darkness makes people frighten... How does the human brain sense changes in the external environment and respond? Previous people discovered that there was an protein on the cell surface, namely the G-protein coupled receptor (GPCR for short), which acted as a "signal force" to send these biological signals to the cells through the downstream G-protein. This discovery later won the Nobel Prize in Chemistry . However, there has been a major issue in the field of GPCR signaling, namely how it activates another signaling pathway, , the repressor protein. Xu Huaqiang led an international team composed of 28 laboratories to analyze the crystal structure of the classic GPCR rhodopsin and repressor protein complex for the first time, and overcome this world-class scientific problem , laying a solid theoretical foundation for the development of more selective drugs.
5-hydroxytryptamine makes people feel happiness and happiness, and is called "happy neurotransmitter", but its disorders can cause depression , schizophrenia , migraine , etc.Xu Huaqiang led the team to analyze the near-atomic resolution GPCR structure of three 5-hydroxytryptamine receptors for the first time in the world, providing clear ideas for drug design and development of related diseases. Over the past 12 years, Xu Huaqiang's team has analyzed the GPCR structures closely related to neural, immune and metabolic diseases of more than .
Xu Huaqiang (second from left) won the "Tan Jiazhen Life Science Achievement Award". Shanghai Institute of Pharmaceuticals provides
"Those who get GPCR will win the world". So far, 40% of the listed drugs target GPCR. The drug target structure and function center of the Shanghai Institute of Pharmaceuticals founded by Xu Huaqiang has now become a leading domestic and international cutting-edge technology platform, cultivating a group of high-level talents for the development of China's biomedical .
"This is probably one of the few platforms in the world. It not only does basic research, but also applies research, and it also encourages the transformation of scientific research results." Xu Huaqiang said. The three new drugs he participated in and led by have entered the clinical trial stage, among which new drugs candidate for steatohepatitis were approved for clinical trials in the United States and China respectively.
["No madness can't survive, scientific research is always for the highest peak"]
In Xu Huaqiang's office, a drug molecular map is updated every year, which lists the 200 most commonly used drugs in the world. "I hope that one day my research will also become part of this picture." Xu Huaqiang told the reporter of Liberation Daily Shangguan News.
"Scientific research is only first, no second." In his opinion, to strive for first place, innovative thinking is the most needed. In the 1990s, parsing the protein structure was a very difficult thing. Because, first, protein molecule needs to be crystallized, and most protein molecules are difficult to crystallize. At that time, this became one of the most troublesome things for Xu Huaqiang. The crystallization conditions of protein are only external factors. Can we start from internal factors? One day, Xu Huaqiang was muttering " internal cause determines external cause" and suddenly came inspiration. Without changing its main properties, if the structure is slightly modified, the protein will indeed be easier to crystallize. The idea of was later "replicated" by many research groups. brought a large number of difficult-to-crystallized protein molecules into the research field, making significant contributions to this field.
The important scientific research results of Xu Huaqiang's research team in recent years. Lai Xinlin Photo
"Luck is very important to scientists, but luck is hard work." Xu Huaqiang said. When he wanted to analyze the structure of rhodopsin and repressor protein complexes, because this "world-class scientific problem" was too difficult, many people were worried for him. He persisted in for 10 years and found the answer.
"Huaqiang is simply not crazy and cannot survive. He always strives to do scientific research for the highest peak." said Xu Wenqing, professor at Shanghai University of Science and Technology, and director of Shanghai Facilities at National Protein Science Research. They have known each other for many years. Once, Xu Wenqing went to the office to visit Xu Huaqiang. He saw that his hair was oily and he had not taken a shower for several days. It turned out that he was solving a problem, so he slept in the office and worked when he woke up.
"Teacher Xu has both passion and determination. He always says that in basic research, you need to have a strong momentum. No matter how many times you fail, you can fight again. " said researcher at the Shanghai Institute of Pharmaceuticals .
Doctoral student Wang Yue still remembers that for the first time, Xu Huaqiang warned students: "It doesn't matter if the experiment failed, you must not fake it. "
Xu Huaqiang (first from right) is guiding students to do experiments. Photo by Lai Xinlin
In the eyes of , director of the Shanghai Institute of Pharmaceuticals, , , Xu Huaqiang is not only a "pure scientist", but also "very responsible" . At the beginning of the COVID-19 outbreak, Xu Huaqiang asked the team members to put the topic at hand first. They lived in the office and sometimes ate instant noodles. After was used for 46 days, and his partners analyzed the separate structure of the RNA replicaase of the new coronavirus and the cryo-electron microscopy structure of the RNA and inhibitor remdesivir complex.In mid-March this year, the epidemic situation in Shanghai was severe. Xu Huaqiang and his team took the initiative to request a blockade in the park, analyzing the high-resolution cryo-electron microscopy structure of the spike protein of the BA.2 variant strain of the new coronavirus, combining with the human receptor ACE2, explaining the molecular mechanism of enhanced infectivity and immune escape from the atomic level, and structurally explaining the immune protection mechanism of the anti-Omickron mutation caused by the first generation of vaccines. provides a theoretical basis for promoting the third dose of the new coronavirus vaccination.
Now, Xu Huaqiang has joined the Shanghai Institute of Pharmaceuticals full-time, and works until 1 a.m. every day. "Life science is full of charm, scientific exploration is my only hobby, and I look forward to the next discovery."
Character introduction: Xu Huaqiang, born in 1964, is an internationally renowned structural pharmacologist. He has published 32 papers in the main journals of "Cell", " Nature " and "Science". His papers have been cited more than 29,000 times and has been rated as a "global high-cited scholar" for many years. His research results were selected as "2014 Top Ten Progress in Chinese Science " and "2015 China's Top Ten Progress in Science and Technology". In 2016, he won the International Protein Society Outstanding Contribution Individual Award, in 2021, he won the "Tan Jiazhen Life Science Achievement Award", and in 2022, he won the "Wu Jieping-Paul Janssen Medical Pharmacy Award".
title image source: Lai Xinlin Photo
Source: Author: Huang Haihua
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