Neural stem cells are present in the adult central nervous systems of all mammals, including humans. In the dentate gyrus of the hippocampus these adult neural progenitor cells proliferate and give rise to functionally integrated granule neurons throughout life. Our laboratory is working on the biology of adult neural stem cells and we are interested in the cellular and molecular mechanisms regulating self-renewal and fate specification of adult neural stem cells, and nerve guidance and synaptic integration of their neuronal progeny of adult neural stem cells in the mature CNS environment. Our laboratory is using an integrated approach to investigate rodent and human neural stem cells both in vitro and in animal models utilizing technologies in molecular biology, biochemistry, cell biology, virology, multiphoton confocal imaging and electrophysiology.
Self-renewal of adult neural stem cells: FGF-2 signaling plays essential roles in the maintenance of the proliferation and multi-potency of adult neural stem cells. Using stem cells derived from adult rodent hippocampus and human surgical tissues, we are investigating underlying signal transduction mechanisms.
Neuronal fate specification and neuronal subtype differentiation: Using an in vitro co-culture assay, we previously demonstrated thahttp://neuroscience.jhu.edu/editprofile.aspt astrocytes derived from adult hippocampus, but not those from adult spinal cord, instruct FGF-2-dependent adult neural stem cells to adapt a neuronal fate. We are currently examining the underlying molecular mechanisms using both molecular and genomic approaches. We are also very interested in mechanisms that control the neuronal subtype differentiation of adult neural stem cells from both rodents and humans and are currently exploring the possibilities to use these cells for degenerative neurological diseases, such as Parkinson's Disease and ALS.
Axon and dendrite guidance of newborn neurons from adult neural stem cells: In collaboration with Dr. Guo-li Ming’s laboratory, we have developed in vitro and in vivo model systems to examine the guidance behaviors of newborn neurons from adult neural stem cells. We are using growth cone turning assay to examine growth cone response of neuronal progeny of adult stem cells to a defined diffusible gradient of guidance cues. In parallel, we are examine the axonal/dendritic guidance of newborn neurons in the adult CNS by manipulation of endogenous neural progenitors with engineered retrovirus in normal and genetically modified mice .
Synaptic integration and plasticity by neuronal progeny of adult neural stem cells: We previously established an in vitro co-culture system where neurons derived from adult neural stem cells can functionally integrated into existing neuronal circuits. Recently we have been able to follow the development of retroviral labeled newborn neurons in vivo. We are currently examining the cellular and molecular mechanisms that regulate the functional integration and plasticity of newborn neurons using electrophysiology and multiphoton confocal imaging approaches.
Professional Experience
1990-1992 Research Assistant, Department of Biology, Peking University; Advisor: Prof. Yisheng Ni
1992-1995 Graduate Research Assistant, Columbia University; Advisor: Dr. Mu-ming Poo
1995-1998 Graduate Research Assistant, University of California at San Diego; Advisor: Dr. Mu-ming Poo
1998-2002 Postdoctoral Research Associate, Howard Hughes Medical Institute at the Salk Institute; Co-advisors: Drs. Charles F. Stevens and Fred H. Gage
2002-present Assistant Professor of Neurology and Neuroscience, Institute for Cell Engineering, Johns Hopkins University School of Medicine
Honors and Awards
1985 Third Prize of National High School Computer Science Competition
1986 Third Prize of National High School Mathematics Competition
1989, 1992 First Prize of Distinguished Student Award of Peking University
1992-1995 Faculty Fellow Scholarship of Columbia University
1998-2002 Howard Hughes Medical Institute Postdoctoral Fellowship
2002 Scholarship for Keystone Symposia entitled "Stem Cells: Origins, Fate and Functions"
2003 Third Prize of BioRad Imaging Competition
2003-2006 Klingenstein Fellowship Awards in the Neuroscience
Professional Memberships
Society for Neuroscience; Society for Experimental Biology and Medicine; International Brain Research Organization
Professional Services:
Journal Peer Reviewer: Cell, Science, PNAS, Neuron, Developmental Biology, European Journal of Neuroscience, Experimental Neurology, Gene Therapy, Journal of Cell Science, Journal of Neurobiology, Journal of Neuroscience, Molecular and Cellular Neurobiology, Neurobiology of Aging, Regenerative Medicine, Stem Cells
Grant Review Group: National Science Foundation (Ad hoc, 2003, 2005); National Institute of Health (ZRG1 SSS-P, 2004; NCF, Ad hoc; 2004, 2005); A*STAR in Singapore (2004,2005), Health Research Board in Ireland (2005).
Peer-reviewed publications
1. Dan, Y., Song, H-j., and Poo, M-m. (1994). Evoked neuronal secretion of false transmitters. Neuron 13, 909-917.
2. Song, H-j., Ming, G-l., Fon, E., Bellocchio, E., Edwards, R.H., and Poo, M-m. (1997). Expression of a putative vesicular acetylcholine transporter facilitates quantal transmitter packaging. Neuron 18, 815-826.
3. Song, H-j., Ming, G-l., and Poo, M-m. (1997). cAMP-induced switching in turning direction of nerve growth cones. Nature 388, 275-279.
4. Fitzsimonds, R.M., Song, H-j., and Poo, M-m. (1997). Propagation of activity-dependent synaptic depression in simple neural networks. Nature 388, 439-449 (leading article).
5. Ming, G-l., Song, H-j., Berninger, B., Holt, C., Tessier-Lavigne, M., and Poo, M-m. (1997). cAMP-dependent axon guidance of netrin-1. Neuron 19, 1225-1235.
6. Sternfeld, M., Ming, G-l., Song, H-j., Sela, K., Soreq, H.E., and Poo, M-m. (1998). Acetylcholinesterase exerts a non-catalytic, nerve growth-promoting activity. J. Neurosci. 18, 1240-1249.
7. Song, H-j., Ming, G-l., He, Z., Tessier-Lavigne, M. and Poo, M-m. (1998). Conversion of neuronal growth cone responses from repulsion to attraction. Science 281, 1515-8.
8. Ming, G-l., Song, H-j., Berninger, B., Inagaki, N., Tessier-Lavigne, M., and Poo, M-m. (1999). Phospholipase C-g and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance. Neuron 23, 139-48.
9. Tamagnone, L., Artigiani, S., Chen, H., He, Z., Ming, G-l,, Song H-j., Chedotal, A., Winberg, M.L., Goodman, C.S., Poo, M., Tessier-Lavigne, M., and Comoglio, P.M. (1999). Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99, 71-80.
10. Ming, G-l. Henley, J., Tessier-Lavigne, M., Song, H-j.*, and Poo, M-m. (2001). Electrical activity modulates growth cone guidance by diffusible factors. Neuron 29, 441-452. (*corresponding author).
11. Song, H-j., Stevens, C.F. and Gage, F.H. (2002). Astroglia induce neurogenesis from adult neural stem cells. Nature 417, 39-44 (leading article).
12. Song, H-j., Stevens, C.F. and Gage, F.H. (2002). Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat. Neurosci. 5, 438-45.
13. Kao, H.T., Song, H-j., Porton, B., Abraham, M., Ming, G-l., Czernik, A.J., Pieribonr, V.A., Poo, M-m., Greengard, P. (2002). A PKA-dependent molecular switch in synapsins regulates neurite outgrowth. Nat. Neurosci. 5, 431-437.
14. Ming, G-l., Wong, S. Henley, J. Yuan, X-b., Song, H-j., Spitzer, N.C. and Poo, M-m. (2002). Adaptation in the chemotactic guidance of nerve growth cones. Nature 417, 411-8 (leading article).
15. Song, H-j., Lie, D., Stevens, C.F. and Gage, F.H. (2003). Reply to: Familial dementia with dentate atrophy and failure of neurogenesis. Ann. Neurol. 53, 421.
16. Dickinson H, Winkler, J., Fisher, L., Song, H-j., Poo, M-m. and Gage, F.H. (2003). Acetylcholine-secreting cells improve age-dependent memory deficits. Mol. Ther. 8, 51-61.
17. Ren, X-r., Ming, G-l., Xie, Y., Hong, Y., Sun, D-m., Wang, Q., Shim, S., Song, H-j., Mei, L., and Xiong, W-c. (2004). Focal adhesion kinase in Netrin-1 signaling. Nat. Neurosci. 7, 1204-1212.
18. Shim, S., Goh, E.L.K., Ge, S-y., Sailor, K., Yuan, J.P. , Roderick, H.L., Bootman, M.D., Worley, P.F., Song, H-j. and Ming, G-l. (2005). XTRPC1-dependent chemotropic guidance of neuronal growth cones. Nat. Neurosci. 8, 730-735.
19. Ko, H. S., von Coelln, R., Ravichandran, S., Kim, S.W. Chung, K.K.K., Pletnikova, O., Troncoso, J.C., Johnson, B., Saffary, R., Goh, E., Song, H-j., Park, B-j. , Kim, M.J., Kim, S.S., Dawson, V. and Dawson, T. (2005). Accumulation of the authentic Parkin substrate, aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J. Neurosci. 25, 7968-78.
20. Lie, D.C., Colamarino, S.A., Song, H-j., Mira, H., Consiglio, A., Desire, L., Lein, E.S., Dearie, A.R., Lansford, H., and Gage, F.H. (2005). Wnt signaling regulates adult hippocampal neurogenesis. Nature 437,1370-5.
21. Ge, S-y., Goh. E.L.K., Sailor, K.A., Kitabatake, Y., Ming, G-l. and Song, H-j. (2006). GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439, 589-593.
22. Barkho, B., Song, H-j., Aimone, B., Kuwabara, T., Nakashima, K., Gage, F.H., and Zhao, X-y. Identification of astrocytes-expressed factors that modulate neural stem/progenitor cell differentiation. Stem Cells and Development (in press).
Reviews
1. Poo, M-m., Dan, Y., Song, H-j., Morimoto, T., and Popov, S. (1996). Calcium-dependent vesicular exocytosis: from constitutive to regulated secretion. Cold Spring Harb Symp Quant Biol. XI, 349-359.
2. Song, H-j., and Poo, M-m. (1999). Signal transduction underlying growth cone guidance by diffusible factors. Curr. Opin. Neurobio. 4, 355-363.
3. Song, H-j., and Poo, M-m. (2001). Cell biology of neuronal navigation. Nat. Cell Bio. 3, E81-E88.
4. Henley, M.G., Tessier-Lavigne, M., Song, H-j., and Poo. M-m. (2001). Growth cone guidance, diffusible factors, and electrical activity. Neuroscientist 7, 271-272.
5. He, Z., Wang, K. C., Koprivica, V., Ming, G., Song, H.-j. (2002). Knowing how to navigate: Mechanisms of semaphorin signaling in the nervous system. Science's STKE, 119 RE1.
6. Goh, E.L.K., Ma, D., Ming, G-l., and Song, H-j. (2003). Adult neural stem cells and repair of the adult central nervous system. J. Hematother. Stem Cell Res. 12, 671-680.
7. Lie, D.C.*, Song, H-j.*, Colamarino, S.A., Ming, G-l., and Gage, F.H. (2004). Neurogenesis in the adult brain: repairing the brain by transplantation for neurodegenerative disorders. Annu. Rev. Pharmacol. Toxicol. 44, 399-421 (* equal contributions).
8. Ming, G-l. and Song, H-j. (2005). Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci. 28, 232-250.
9. Ma, D-k., Ming, G-l., and Song, H-j. (2005). Glial influences on stem cell development: cellular niches in adult neurogenesis. Curr. Opin. Neurobio. 15, 514-520.
10. Song, H-j., Kempermann, G. Overstreet Wadiche, L., Zhao, C-m., Schinder, A.F., and Bischofberger, J. (2005). New Neurons in the Adult Mammalian Brain: Synaptogenesis and Functional Integration. J. Neurosci. 25, 10366-10368.
11. Sailor, K.A., Duan, X., Ming, G-l., and Song, H-j. (2006). Neurogenesis as a potential therapeutic strategy for neurodegenerative disorders. Exp. Opin. Biol. Thera. (invited review).
12. Kitabatake, Y., Ming, G-l, and Song, H-j. (2006). Adult Neurogenesis and Hippocampal Memory Function. Neurosurg. Clin. N. Am. (invited review)
Current Research Support
1. Klingenstein Fellowship Awards in the Neuroscience (PI) 07/01/03-06/30/06
The Esther A. & Joseph Klingenstein Fund
Title: Mechanisms of adult neurogenesis in the dentate gyrus
The major goal of this project is to identify molecular mechanisms regulating proliferation and differentiation of adult neural stem cells in the dentate gyrus of the rodent hippocampus in the context of epilepsy.
2. RO1 NS047344 (PI) NIH/NINDS 09/30/03-06/30/08 Title: Characterization of Neuronal Differentiation by Adult CNS Progenitors
The major goal of this project to characterize and compare the differentiation and neuronal maturation of cultured clonal neural progenitors derived from the hippocampus and spinal cord of young adult rats and to investigate the intrinsic neurogenic potentials of neural progenitors in the spinal cord of young adult rats.
3. 7
RO1 AG024984 (PI) NIH/NIA 9/30/04-8/31/09
Title: Regulation of adult neurogenesis during aging
The major goal of this project is to investigate intrinsic and extrinsic mechanisms regulating adult hippocampal neurogenesis during aging.
4. The Robert Packard Center for ALS Research at Johns Hopkins (PI) 12/1/04-11/30/06
Title: Development of an in vitro model of ALS using stem cells
The major goal of this project is to develop an in vitro culture system with adult neural stem cells derived from mouse spinal cord or brains and mouse embryonic stem cells to examine the role of astroglia-motor neurons interaction in ALS.
