Excel High School
Vladimir Tkachev and Nathaniel Goble
Stanley Center for Psychiatric Research | Pan Lab
Matthew understood when he applied to BSSP that biomedical research was a team sport, and he wanted in. In his application, he said, "The collaborative environment will not only enhance my ability to learn but also provide me with the opportunity to work with others and gain new perspectives on different fields." At the Broad, Matthew was matched with researchers at the Stanley Center for Psychiatric Research to conduct cutting-edge research on Schizophrenia. This severe psychiatric disorder affects roughly 24 million people worldwide. While most drugs on the market for Schizophrenia treat symptoms such as hallucinations and delusions, these patients suffer from cognitive impairment and sleep impairment. During sleep, brief bursts of brain activity, known as sleep spindles, occur during stage 2 of non-REM sleep and are essential for memory consolidation and cognitive function. Patients with Schizophrenia show reduced sleep spindle density, which may account for deficits in both sleep and cognitive function. Past research has shown that one of the risk genes that significantly increase a patient's risk of developing Schizophrenia is a loss-of-function mutation, which is the CACNA1I gene, which encodes for Cav.3.3 voltage-gated calcium channels. Cav.3.3 voltage-gated calcium channels are highly abundant in the thalamic reticular nucleus (TRN), which generates sleep spindles positively correlated with learning and memory. Matthew and his partner Sybille aimed to target Cav3.3 channels with novel therapeutics and rescue their deficits in vitro. By the end of the summer, they successfully characterized two compounds capable of modulating the calcium concentration of HEK293 cells. Simultaneously, their mentors showed that these compounds rescued sleep spindle deficits in mice, corroborating the findings made by Matthew and Sybille. Aside from performing novel research, Matthew learned about the importance of science communication. He says “ BSSP taught me the importance of communicating with people in an effective way that they will understand my ideas or thoughts. By the end of the summer, Matthew learned what it meant to be a part of the Broad biomedical research effort and what a career in science could be like for him.