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Hongjun Song, Ph.D.

Photo of Dr. Hongjun Song, Ph.D.

Director, Stem Cell Program

Professor of Neurology

Research Interests: Adult neural stem cells, neurogenesis, schizophrenia, bipolar disorder, major depression

Background

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.

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Titles

  • Director, Stem Cell Program
  • Professor of Neurology
  • Professor of Neuroscience

Departments / Divisions

Education

Additional Training

Ph.D., University of California at San Diego, La Jolla, CA, 1998, Biology

M.A./M.Phil, Columbia University, New York, NY, 1995, Biology

B.S., Peking University, Peking, Peoples Republic of China, 1992, Biology

Residency, The Salk Institute for Biological Science, La Jolla, CA, 2002, Neuroscience

Research & Publications

Research Summary

The Song lab studies mechanisms underlying mammalian neurogenesis, especially the cellular and molecular mechanisms that adult neural stem cells and their development in the mature central nervous system. The lab uses an integrated approach to study rodent and human neural stem cells in cell culture and in animal models utilizing technologies in molecular biology, cell biology, biochemistry, epigenetics, virology, histology, in vivo multiphoton confocal imaging, electrophysiology, mouse genetics and animal behaviors.

Current projects include characterizing properties of adult neural stem cells and neurogenesis; investigating intrinsic and extrinsic mechanisms regulating fate choice of adult neural stem cells and development of newborn neurons in the adult brain; characterizing contributions of newborn neurons at multiple levels in the adult brain, including single-cell electrophysiology in acute slices, local neuronal circuitry integration in vivo using optogenetic and multi-electrode recordings, and contribution to specific animal behaviors; exploring epigenetic mechanisms regulating adult neural plasticity.

The Song lab also is interested in understanding how defects in adult neurogenesis and epigenetic mechanisms contribute to mental disorders.

Lab Website: Hongjun Song Laboratory

Selected Publications

View all on Pubmed

Guo, J.U., Su, Y., Shin, J.H., Shin, J., Li, H., Xie, B., Zhong, C., Hu, S., Le, T., Fan, G., Zhu, H., Chang, Q., Gao, Y., Ming, G.L., Song, H. (2014). Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nature Neuroscience 17, 215-22. [PMC in progress]

Song, J., Sun, J., Moss, J., Wen, Z., Sun, G.J., Hsu, D., Zhong, C., Davoudi, H., Christian, K.M., Toni, N., Ming, G.L., and Song, H. (2013). Parvalbumin interneurons mediate neuronal circuitry-neurogenesis coupling in the adult hippocampus. Nature Neuroscience 16, 1728-1730. [PMC in progress]

Jang, M., Bonaguidi, M.A., Kitabatake, Y., Sun, J., Song, J., Kang, E., Jun, H., Zhong, C., Su, Y., Guo, J.U., Wang, M.X., Sailor, K.A., Kim, J.Y., Gao, Y., Christian, K.M., Ming, G-l., and Song, H. (2013). Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. Cell Stem Cell 12, 215-23. [PMC3569732]

Song, J., Zhong, C., Bonaguidi, M.A., Sun, G.J., Hsu, D., Gu, Y., Meletis, K., Huang, Z.J., Ge, S., Enikolopov, G., Deisseroth, K., Luscher, B., Christian, K., Ming, G-l., and Song, H. (2012). Neuronal circuitry mechanism regulating adult quiescent neural stem cell fate decision. Nature 489:150-4. [PMC3438284]

The Huntington's Disease iPSC Consortium. (2012). Induced pluripotent stem cells from patients with Huntington's disease show CAG repeat expansion associated phenotypes. Cell Stem Cell 11, 264-78. [PMC3804072]

Academic Affiliations & Courses

Graduate Program Affiliation

Neuroscience
Cellular and Molecular Medicine
Human Genetics and Molecular Biology

Activities & Honors

Honors

  • Distinguished lecture, German Cancer Research Center (DKFZ), 2012
  • Rising Star Award, International Mental Health Research Organization, 2009
  • Plenary lecture, Presidential Symposium at the 10th ISSCR Annual Meeting, 2012
  • Plenary lecture, Presidential Symposium at the 5th ISSCR Annual Meeting, 2007
  • Young Investigator Award, Society for Neuroscience, 2008
  • Special Lecture, Society for Neuroscience Annual Meeting, 2013
  • Gail F. Beach Memorial Visiting Lectureship, University of Miami Miller, 2013
  • Terrence Doaln Lecture, Waisman Center University of Wisconsin-Madison, 2012
  • Klingenstein Fellowship Awards in the Neuroscience, 2003
  • McKnight Scholar Award, 2006
  • Inaugural Young Investigator Award, Chinese Biological Investigators Society, 2007
  • Independent Investigator Award, NARSAD , 2008
  • Jacob Javits Neuroscience Investigator Award, NINDS, 2013

Memberships

  • Cellular and Molecular Neurobiology, 2011
    Editorial board
  • Faculty of 1000 Biology, 2009
  • Frontiers in Biology, 2012
    Editor in Chief
  • Journal of Biochemistry, 2010 - 2015
    Editorial board
  • Molecular Brain, 2008 - 2010
    Editorial board
  • National Science Review, 2014
    Editorial board
  • Neuroepigenetics, 2014
    Editorial board
  • Neurogenesis, 2014
    Editorial board
  • Neurogenesis and Cell Fate (NCF), 2008 - 2012
    NIH study section standing member
  • NIH study sections (~ 6 ad hoc study sections per year), 2006
  • Society for Neuroscience, 2008 - 2011
    Program Committee Member
  • Stem Cell Policy and Ethics Program (SCOPE) of the Phoebe R. Berman Bioethics Institute at Johns Hopkins University, 2006 - 2009
    Member
  • The Journal of Neuroscience, 2008 - 2013
    Associate Editor

Professional Activities

  • Director, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 2010
    Stem Cell Program
  • Graduate student, Columbia University, 1992 - 1995
  • Graduate student, University of California at San Diego, 1996 - 1998

Videos & Media

The Stem Cell Biology Program at Johns Hopkins’ Institute for Cell Engineering

Hongjun Song | Using Stem Cells in the Brain to Study Mental Disorders

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