On July 10, Prof. YIN Shankai and Prof. SHI Haibo’s team from Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) published their research paper in the journal Nature as the first authors and the first corresponding authors, proposing for the first time the core concept that glutamate functions as a positive allosteric modulator for acid-sensing ion channels (ASICs) to exacerbate neurotoxicity, and increases the affinity of ASICs for protons and their open probability, thus aggravating ischaemic brain injury. Their research revealed a unique glutamate - ASIC binding pattern that is proved to cause irreversible damage and death of neuronal cells. And, by leveraging such technologies as computer simulation, high-throughput virtual screening, site-directed mutagenesis, and cell electrophysiology, the research team revealed a bona fide glutamate-binding cavity in the extracellular domain of ASIC. Also, the authors successfully synthesized a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents. Compared to the control group, LK-2 reduces the infarct volume by about 53.6% and improves sensorimotor recovery in a mouse model of ischaemic stroke. This implies that LK-2, as a small molecule that inhibits glutamate - ASIC binding, has the potential to alleviate the neuronal damage in ischemic stroke patients and improve their neurological function. Prof. YIN Shankai and Prof. SHI Haibo from Shanghai Sixth People's Hospital are the co-corresponding authors of the academic paper, while Dr. LAI Ke and Dr. LIU Zhenqi are the co-first authors. Prof. XU Tianle and his team from SJTUSM, as well as scientists and researchers from the University of Toronto in Canada, provided strong support for the research. The research finding marks a new level of collaborative basic and clinical research and interdisciplinary innovator development at SJTUSM.

Back in 2013, SJTUSM proposed to build an “interdisciplinary and innovative education” system for neuroscience graduate students, which spans medicine, science, and engineering horizontally, as well as basic medicine, clinical medicine, and pharmacy vertically. Prof. XU Tianle, then chancellor of Shanghai Jiao Tong University School of Basic Medicine (SJTUSBM), led the implementation of the “Shanghai Program for Graduate Education & Innovation and Pilot Project for Comprehensive Reform of Academic Degree Graduate Education”, aiming to accelerate the system in three aspects. Firstly, efforts were made to build an integrated “Frontiers of Neuroscience” course, and edit or co-edit some teaching materials including “Modern Neurobiology”, a textbook published by Science Press for graduate students in the 14th Five-Year Plan period (as editor in chief), “Nervous System”, a textbook for undergraduate students under the Ministry of Education’s 101 Plan (as deputy editor in chief), and “Introduction to Neurobiology” (as co-editor). Secondly, a new “Shanghai Key Laboratory for Analysis of Emotional Brain Function and Disorder Intervention (Preparatory)” was established to create an interdisciplinary innovator training site. In addition, various forms of interdisciplinary academic exchange activities such as literature reviews, progress reports, and leaderboard presentations were carried out to cultivate students’ ability to think and solve problems across disciplines, fully enhancing their innovative thinking, capabilities, and strengths. These initiatives helped resolve the three major challenges in the training of graduate students in neuroscience: No.1, the lack of interdisciplinary knowledge reserves among graduate students and the failure to update their textbooks prevented them from keeping up with the cutting-edge methods and latest research findings; No.2, the research teams in basic and clinical neuroscience were separated, and there was a lack of communication and cooperation between basic and clinical PIs, resulting in a significant disconnect between biological research and clinical medicine; and No.3, there was a lack of interdisciplinary academic exchange platforms, severely limiting the driving force behind graduate research and innovation.

Based on the system, the Prof. YIN Shankai and Prof. SHI Haibo team from Shanghai Sixth People’s Hospital developed a unique approach to education of medical graduate students: “focusing on the major clinical and scientific issues and combining cutting-edge basic scientific methods to solve them”. Firstly, focus was put on the major scientific issues in clinical practice, by encouraging graduate students to discover the issues through their practical clinical work, which should be of high scientific value and practical significance, like disease mechanisms that have a wide impact and development of new therapies. Secondly, the cutting-edge basic scientific methods were integrated, and the graduate students were encouraged to study the cutting-edge basic sciences such as molecular biology, genetics, and bioinformatics, master the necessary experimental techniques and theoretical knowledge, and apply what they had learned to the research of clinical issues; and mentors with rich clinical experiences and research background were assigned to provide graduate students with personalized guidance and advice. Thirdly, interdisciplinary training between clinical and basic sciences was promoted, encouraging graduate students to participate in multidisciplinary teams, solve complex problems through teamwork, and improve their collaborative abilities and comprehensive qualities. Actually graduate students were requested to participate in clinical practice and laboratory research to enhance their practical skills and problem-solving abilities.

Research Team of the Department of Otolaryngology - Head & Neck Surgery at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Through this series of measures, SJTUSM resolved the three major challenges in the training of graduate students in medicine: No.1, the lack of interdisciplinary knowledge reserves among graduate students and the failure to update their textbooks prevented them from keeping up with the cutting-edge methods and latest research findings; No.2, the research teams in basic and clinical medicine were separated, and there was a lack of communication and cooperation between basic and clinical PIs and between graduate students, resulting in a significant disconnect between biological research and clinical medicine; and No.3, there was a lack of interdisciplinary academic exchange platforms, severely limiting the driving force behind graduate research and innovation. In a nutshell, this unique approach to education of medical graduate students emphasizes the close integration of clinical and basic sciences, focuses on the cultivation of practical and innovative abilities, and is expected to develop a group of talented people in scientific research and clinical practice. While building an integrated, multidisciplinary education system for graduate students in neuroscience, SJTUSM deeply linked itself to the strategic plans of our country and Shanghai in connection with neuroscience. Relying on its profound foundation in basic and clinical medicine, as well as SJTU’s unique interdisciplinary advantages in medicine, pharmacy, science, engineering, and informatics, it launched and accelerated the construction of a “disease oriented platform for interdisciplinary integration of neuroscience” in 2018, aiming to explore new frontiers of neuroscience through interdisciplinary cooperation. At the end of the same year, with the support of the Shanghai Municipal Education Commission’s Local Plan for Construction of High level Universities, SJTUSM successfully set up a total of 20 innovation teams, including those in neuroscience, marking a significant transformation in its research organization model. With the numerous initiatives taken by SJTUSM, the hospitals affiliated to it have achieved many excellent results through interdisciplinary cooperation, trained a large number of clinical medical graduate students with cutting-edge basic research perspectives, and contributed to the publication of a series of high-level articles. Shanghai Sixth People’s Hospital, for example, has trained a large number of such students who independently developed an all-new academic idea from the perspective of bilirubin local ototoxicity induced hypoxic-ischemic brain injury. The first author of the Nature publication, Dr. LAI Ke, a postdoctoral fellow from Shanghai Sixth People’s Hospital (co-supervised by Prof. YIN Shankai), initiated his research on neurological dysfunction caused by ischemia and hypoxia as directed by his doctoral supervisor Prof. SHI Haibo. Inspired by Prof. XU Tianle’s lecture on “Frontiers of Neuroscience”, he developed a strong interest in ASIC related research directions and discovered a new mechanism of ASIC mediated neonatal bilirubin induced neurological damage. This research finding was published in Science Translational Medicine (2020), with Dr. LAI Ke as the first author and Prof. XU Tianle’s doctoral student SONG Xinglei as the co-first author. In addition, LIU Hanwei from Shanghai Sixth People’s Hospital, the first author (supervised by Prof. YIN Shankai) and Dr. LAI Ke, the co-first author, published another research finding in Neuron (2023), unveiling a new mechanism by which bilirubin acts as an agonist to directly activate TRPM2 channels and exacerbate brain damage. The research results were published in Neuron (2023). Prof. YIN Shankai led his team to effectively implement the training model for medical graduate students, convey the new independent academic thoughts, and conduct the SJTUSM philosophy of “interdisciplinary and innovative education”.

Shanghai Jiao Tong University School of Medicine strives to improve the top-level design of “organized scientific research”, strengthen the mission-driven, problem-oriented research, increase the strength of open cooperation in scientific research, and deepen the domestic and international cooperation through joint research institutions, closer exchanges and collaboration among researchers, and enhanced student exchanges and practices, all aiming to develop the medical talents with international perspectives, and contribute Chinese wisdom and strength to the human health community as driven by technological innovation.