A molecule that has been silent for about two hundred years have suddenly become the "new star" in the immunometabolism. When Samuel Baup discovered itaconate in distilled citric acid, he probably did not expect that this small molecule which was "abandoned" by the tricarboxylic acid cycle is now playing an important role in the immunometabolism. Particularly, itaconate not only fights bacterial infection but also inhibits pathogen-induced inflammation. Itaconate is only one of the treasure troves of metabolites, in which there are still many unknowns worth exploring. Meixin Chen, together with her team, will continue to work in the immunometabolism, take up the challenges and try to discover links between metabolism and immunity, which will provide more possibilities for the treatment of pathogen infection-related diseases.
Institute of Infectious Diseases at Shenzhen Bay Laboratory
Principal Investigator
Research areas:
Our long-term objectives are to decipher the anti-bacterial or anti-viral effect of intracellular metabolism. Our research focused on understanding the pathogenesis of pathogens (bacteria and virus) and how innate immunity or cell-autonomous immunity resists microorganisms.
Some specific research interests of the lab include:
1. Pathogenesis of Salmonella.
2. Immune responses to Salmonella infection.
3.Screening and identification of new antimicrobial metabolites.
There is no easy way for scientific research, but I did not hesitate too much in choosing to embark on the path of the scientific research. In retrospect, I met good teachers with great teaching skills who provided very useful guidance when I was in high school. The one particularly unforgettable is Ms. Su Jianmin, my biology teacher in junior high school. Her teaching style is lively and she is also very knowledgeable. While I was amazed at the mystery of life, she opened the door to life science for me as a child. When I filled in the college application form, I naturally applied for the biology major.
During my master's and doctoral studies, I was lucky enough to enter the laboratory of Professor Cui Jun at Sun Yat-sen University. Cui was a young PI in his early thirties at the time and very energetic. The laboratory atmosphere was also very good. We communicated with each other equally, and the relationship was harmonious. I think I did not have a good scientific foundation at the beginning, but Cui was very patient and would guide us carefully to answer our questions. Cui helped me a lot, and more importantly, I began to gradually build up my confidence in doing scientific research and focus on my research projects without distractions and slackness.
After graduating with a doctor's degree, I came to New Haven on the other side of the ocean and joined the Yale School of Medicine where the academic atmosphere was very strong. I continued my post-doctoral research in the laboratory of Academician Jorge E.Galán. Professor Galán is from a small town in Argentina and has been engaged in the microbe and immunity-related research for more than thirty years. He worked hard for years to take root in the US and has done groundbreaking works. He was famous especially for discovery of the type III secretion system (T3SS) of Salmonella. Jorge E. Galán was elected academician of National Academy of Sciences and academician of the National Academy of Medicine in the US in 2012 and 2019, respectively. When I first arrived in the US and was still trying to adapt to the challenges brought by cultural differences, my advisor had put forward high requirements for the subject and hoped that I could make a breakthrough in a short time. This brought me great pressure at the time. But now I am very glad that I could calm down, withstood the pressure, and quickly kept up with the pace of Professor Galán's laboratory. My topic is mainly to study immune metabolism and anti-infective immune regulation. We found the antibacterial pathway of itaconate from mitochondria in the body. After the efforts from countless days and nights, the results were finally published in Science. Looking back on this learning experience, I think it is especially precious. Although Professor Galán has stepped into his 60s, his enthusiasm for scientific research seems to have only increased. Whether wind or snow, he was the first to arrive at the laboratory almost every day. In our one-to-one "morning meeting" every week, I could see his eyes light up as he talked about scientific research, and sometimes he talked for more than two hours while remaining energetic to carry on. Professor Galán sometimes did experiments with me and discussed a lot of the details of the experiments. I think all of these have had a profound and very positive impact on me. On one hand, I feel the charm of scientific research more deeply; on the other hand, I have gradually begun to look forward to seeing what the laboratory looks like after I become an independent PI. I hope I can keep my original intention in mind, enjoy it, and have more breakthrough results.
The opportunity of joining Shenzhen Bay Laboratory came from a friend's "cloud" recommendation. Before returning to China, I learned about the new research institution in Shenzhen Guangming Science City from a friend, and "cloud"-visited the laboratory's scientific research environment, which left a deep impression on me. I think it is very meaningful to have the opportunity to participate in the growth and construction of a young organization as a young PI. Many energetic and young talented people in the field of life science are gathered here. I hoped to join them and jointly build an internationally recognized scientific research platform. Coming to Shenzhen has another meaning for me. Several decades ago, my parents left their hometown for Shenzhen. Now I also chose this city to start my academic career, which may be a kind of inheritance. Shenzhen is open, inclusive, and fair. I like Shenzhen's attitude and pace, and we have more opportunities to make innovative achievements here.
One of the main interests of our team now is to focus on the functions of host metabolites and metabolic enzymes in the immune system. In the earlier stage, we have found that they cannot only regulate metabolism to provide energy, but also have some antibacterial and antiviral functions. These metabolites are like an exhaustless treasury, and there are still many unknowns to be discovered. We hope that more partners who love research in the field of life science will work with us to build an international first-class laboratory and do the work that is recognized by everyone.
Biography：
Dr. Meixin Chen earned her Ph.D. in Cell Biology from Sun Yat-sen University in 2018. She joined the laboratory of Dr. Jorge E. Galán, a member of the USA National Academy of Science, at Yale University School of Medicine as a postdoctoral researcher, during which she focused on understanding of how pathogens interact with their hosts. Dr. Meixin Chen and her colleagues found that the mitochondria-derived metabolite itaconate targeted Salmonella containing vacuoles. This study placed the intracellular metabolism in the center of cell-autonomous defenses and was published in Science. Dr. Meixin Chen has been studying innate immune responses for many years, and in addition to Salmonella, she has worked on how DNA virus or RNA virus interacts with their hosts. Dr. Meixin Chen, as a first author, has published several articles in Science, Molecular Cell, and Advanced Science.
Meixin Chen, et al. Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella. Science 369.6502 (2020): 450-455.
Meixin Chen, et al. TRIM14 inhibits cGAS degradation mediated by selective autophagy receptor p62 to promote innate immune responses[J]. Molecular cell, 2016, 64(1): 105-119.
