＂Medical scientist＂ Xu Qi： Aiming at the familiar ＂enemy＂ in the field of brain diseases

CCTV News:Xu Qi, a researcher at the Institute of Basic Medicine, China Academy of Medical Sciences, has a cheerful personality, good eloquence and passion for scientific research. She has been engaged in the research on the pathogenesis of severe mental and neurological diseases for a long time. She reveals depression and breaks through the worldwide problems. Xu Qi won the honorary title of "China Young Female Scientist" at the 14th "China Young Female Scientist Award" ceremony jointly organized by All-China Women’s Federation and China Association for Science and Technology.

Xu qi

As the "ultimate territory" for human beings to understand themselves, there are still too many mysterious areas waiting for new cultivation in the field of neuroscience, and the pathogenesis of severe mental illness is one of them. What happens in a person’s brain when he suffers from severe mental and neurological diseases? What is the mechanism that affects the body? For these unsolved mysteries, Xu Qi, a researcher at the Institute of Basic Medicine of China Academy of Medical Sciences, led the team to carry out a series of in-depth research.

I went from clinical medicine to basic research on diseases, and I did it for 20 years — — Talking about the "career change" in that year, Xu Qi recalled, "Due to the limited level of medical development, doctors can only alleviate the progress of diseases for most patients, but can’t really cure them. Many times, doctors will feel deeply powerless in the face of patients who are in deep pain or even dying, so I really wanted to explore and solve some problems at the root of diseases, so I walked into the laboratory."

Because of this, unlike many scientists who do research based on basic problems, Xu Qi defines herself as a "medical scientist" and always aims at solving practical clinical problems. For many years, Xu Qi has been engaged in the research on the pathogenesis of severe mental and neurological diseases, whether it is schizophrenia, depression or epilepsy — — None of her "enemies" can be taken lightly — — Their pathogenesis and causes are extremely complicated. "Genetics is actually applied to brain diseases, and all of them are looking for diseases that may be caused by some defects at the genome level, but there is often a long way to go before clinical treatment. Ultimately, it requires the joint efforts of many disciplines to achieve diagnosis and treatment."

In recent five years, Xu Qi and his team have focused on a special category of epilepsy — — Because conventional antiepileptic drugs are ineffective, this subclass is called "drug-refractory epilepsy" in clinic. "We finally found that the current drugs are ineffective because the pathogenesis of this kind of patients is different from other epilepsy. The problem of patients is not the ion channel of brain neurons, but the Hsp90&beta in astrocytes; The abnormal expression of protein leads to excessive degradation of glutamate transporter, which eventually leads to the accumulation of excitatory neurotransmitter glutamate in the brain. " Xu Qi said.

Only by finding the root cause can we find the drug target. Since then, Xu Qi and her team have found that Hsp90 inhibitor 17AAG combined with another small molecule compound has a remarkable anti-epileptic effect, achieving a 100% control rate in the rodent model of epilepsy, thus taking a solid step on the road to defeating the "enemy" of intractable epilepsy. This not only expands the pathophysiological mechanism of intractable epilepsy, but also provides a new idea for the treatment of intractable epilepsy such as temporal lobe epilepsy. This research result was also named as "the highlight of global new drug discovery in the month" in 2017 by the Nature Reviews Drug Discovery.

Facing another powerful "enemy" — — Xu Qi needs to overcome more obstacles in the work of finding susceptibility genes for depression. Depression is a typical disease with multiple genes and complex traits. Unlike monogenic diseases, we can find out the cause of the disease as long as we find a gene defect. From the perspective of genetic research, the usual way to find the pathogenic genes in polygenic diseases such as depression is to screen among a bunch of possibilities of "A+B", "B+C" and "C+D". "But it often makes ‘ The real murderer ’ At large. " Xu Qi decided to change her previous thinking, but to work hard on the samples first. In the study of heredity, Xu Qi found that it is an extremely important success factor to stratify samples and make them pure. Finally, through genome-wide sequencing technology, in a genetic study on female recurrent major depression, Xu Qi’s team found two "missing" genes related to depression.

In the next research, Xu Qi said that she would still focus on the familiar "enemies" in the field of neurological diseases from the clinical orientation. "The next thing I want to solve is the diagnostic marker of Alzheimer’s disease." Xu Qi revealed, "Although the disease can be diagnosed clinically now, it is too late for the patient’s treatment when it is diagnosed clinically, and the doctor is exhausted. I hope that the diagnostic window of Alzheimer’s disease can be moved forward by scientific means for 5-10 years, giving patients more time for prevention and treatment. "

While solving one brain disease problem after another, Xu Qi never forgets to enjoy exploring the unknown possibilities of science. "At present, I am imagining how to combine wearable devices to prevent diseases, even ‘ Maintenance ’ Brain. For example, as we girls are afraid of aging and love beauty, as a brain, we may consciously go from a young age ‘ Maintenance ’ It may actually prevent the occurrence of various brain diseases. " Xu Qi said, "This is also the next research topic that excites me." (Clue source: Propaganda Department of All-China Women’s Federation)