Schizophrenia [SZ] and bipolar disorder [BP] are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. In the lab of Dr. Akira Sawa, we showed the miR-124-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered upregulation of miR-124 in biopsied neuronal cells and postmortem prefrontal cortex from patients with SZ and BP. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissection, we generated a mouse model that upregulates miR-124 in the medial prefrontal cortex, which includes brain regions homologous to subregions of the human prefrontal cortex. We demonstrated that upregulation of miR-124 increases GRIA2- lacking calcium permeable-AMPARs and perturbs AMPAR-mediated excitatory synaptic transmission, leading to deficits in the behavioral dimensions shared between SZ and BP.
Questions & Answers
Why did you choose Johns Hopkins for your work? I was initially drawn to The Johns Hopkins University because of its incredible history of scientific and clinical excellence. Upon interacting with the spectacular faculty, staff and students in the biomedical engineering department, I was fully convinced that Hopkins was the place for me to pursue my Ph.D. training. What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received? I feel honored to receive this award and encouraged to pursue an academic career. It is an important recognition of the hard work of many people who contributed to the project. Admiring the pioneering spirit of Dr. David I. Macht, I am honored to be able to carry on his legacy in a small way. What contributed to your project’s success? (Special skills, interests, opportunities, guidance, etc.) I am grateful to my mentors who supported me throughout my graduate career. My thesis adviser, Dr. Akira Sawa, gave me scientific freedom to explore my own ideas, unwavering support and scientific guidance. I also deeply appreciate other mentors including Drs. Richard Huganir, Patricia Janak and Nilanjan Chatterjee for their incredible scientific insights and support. What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Hopkins? I appreciate Hopkins for organizing Young Investigators’ Day. It brings a great motivation/recognition to young investigators at Hopkins and gives them the confidence to continue to tackle challenging scientific questions. It can also be the day for them to share their scientific ideas and challenges with other researchers who might not otherwise hear about their work. What has been your best/most memorable experience while at Hopkins? Other than many joyful experiences in the lab, my best experience at Hopkins was during my first year in the human anatomy lab, which gave me a sense of awe for the complexities of the human body. My most unforgettable experience at Hopkins was when I was mentored by Dr. David T. Yue, until he passed away. He was not only an amazing scientist but also a genuinely caring mentor. What are your plans over the next year or so? Graduating, looking for faculty positions, etc.? I plan to graduate within the next few months, and then join a new lab as a postdoc to see where science takes me next. Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences? Fulfilling my mandatory military service on the forefront was a life-changing experience for me. It gave me clarity to distinguish the most and least important things in my life. Indeed, trivial things just fall away in the face of death, leaving only what is truly important.