The research in the Song laboratory focuses on understanding mechanisms regulating neural stem cells and neurogenesis in the mammalian brain. Using neural stem cells as tools, the team explores molecular mechanisms underlying mental disorders with the goal of developing novel strategies for treatment of degenerative neurological disorders. The researchers use an integrated approach using molecular biology, biochemistry, epigenetics, genomics, mouse genetics, immunocychochemistry and immunohistology, confocal and electron microscopy, electrophysiology and animal behavior. Dr. Song and his colleagues have made significant contribution to understanding of adult neurogenesis process in rodent models, including demonstration of radial glia like precursors as one type of self-renewing and multipotent adult neural stem cells and their regulation by neuronal activity. Dr. Song and his laboratory have also made significant contributions to understanding of epigenetic DNA modifications in the adult brain, and have established pipeline for high-throughput sequencing analysis, including RNA-seq, Chip-seq and Bisulfite-seq with all bio-informatic analyses built in-house.
The group has also been using adult neurogenesis as an in vivo experimental model system to address the role of risk genes for mental disorders in neuronal development. For the past 10 years, they have focused studies on one gene named Disrupted-in-Schizophrenia 1 (DISC1). Dr. Song and his team have identified multiple role of DISC1 in regulating different aspects of adult hippocampal neurogenesis, including neuronal morphogenesis, axonal targeting and dendritic development and have provided the first experimental evidence to support the critical role of DISC1 in regulating synapse formation in vivo. They have also translated their basic finding on DISC1 signaling from animal models to humans. For example, in collaboration with Danny Weinberger’s laboratory, the Song lab showed interaction between DISC1 and GABA signaling, which they identified to regulate adult neurogenesis in mice, also affects risk for schizophrenia in human cohort from human genetic analyses and affects human hippocampal connectivity and function based on fMRI studies of humans.
Dr. Song has also been using patient-derived iPSCs as models for understanding mechanisms underlying mental disorders and neurological disorders for the past six years. He and his colleagues have published the first report of iPSC lines from schizophrenia patients of Pedigree H. During the past four years, they have generated additional iPSC lines from Pedigree H and more important, generated multiple isogenic lines with genetic editing. In addition to DISC1 studies, Dr. Song’s laboratory has been helping other colleagues at Hopkins for iPSC studies and has generated well over 100 iPSC lines for different disorders. They have also been involved in large consortium for collaborative studies such as the Huntington’s disease iPSC consortium.
Dr. Song has mentored a number of graduate students, postdoctoral fellows, clinical fellows and undergraduate students. The laboratory’s graduate students and postdoctoral fellows have received fellowships from NIH (F31 and K99) and private foundations. Two of Dr. Song’s graduate students have received both Harold M. Weintraub Graduate Student Award and Peter (2009, 2011) and Patricia Gruber International Research Award in Neuroscience from Society for Neuroscience (2012, 2013). He has also co-mentored K08, K03 and R25 awards for clinical fellows, and seven of his previous trainees are now assistant professors in different universities.