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Faculty & Research

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Hongjun Song

Department Affiliation Primary: Neurology
Secondary: Neuroscience
RankProfessor
Director, Stem Cell Program at ICE
Phone Numbers443-287-7499
Lab: 443-287-7499
Fax: 410-614-9568
Emailshongju1@jhmi.edu
School of Medicine Address733 N. Broadway
MRB 759
Baltimore MD 21205
Link to Lab Homepage
Hongjun Song

Research Topic: Neurogenesis and Neuro-epigenetics

​We are interested in understanding novel mechanisms regulating structural and functional plasticity in the mammalian center nervous system.  There are two major topics in the laboratory: one is on mammalian neural stem cells and neurogenesis; and the other is on epigenetic mechanisms in the mammalian nervous system. Our laboratory is using integrated approaches to address the questions, including technologies in molecular biology, cell biology, biochemistry, epigenetics, genomics, bioinformatics, virology, histology, in vivo multiphoton confocal imaging, electrophysiology, mouse genetics and animal behaviors. 

(1). Neural stem cells and neurogenesis: Adult neurogenesis occurs in unique microenvironment (niche) and recapitulates the complete neural developmental process in a mature central nervous system, including proliferation and differentiation of neural stem cells, neuronal development and synapse formation, maturation and maintenance. Using retrovirus- and mouse genetics-based strategies, we are interested in identifying both intrinsic and extrinsic mechanisms regulating behaviors of adult neural stem cells and governing synaptic integration of newborn in the adult brain in vivo, using single-cell RNA-seq and clonal lineage-tracing and genetic manipulations. We are addressing the function of adult neurogenesis at multiple levels, including single-cell electrophysiology in acute slices, optogenetics and multi-electrode recordings in vivo, and animal behavior analysis. We have also extended our studies of neural stem cells and neurogenesis to other systems, including embryonic neurogenesis in the hypothalamus.  

(2). Neuro-epigenetics: DNA methylation at 5-cytocine has been traditionally considered as very stable epigenetic marks in post-mitotic cells. We recently show that neuronal activity induces active DNA demethylation in post-mitotic neurons in the adult brain in vivo.  We further identified an activity-induced active DNA demethylation pathway in neurons, involving conversion of 5-methylcytosine to 5-hydroxylmethylcytosine by TET, followed by base-excision repair. We are interested in identifying molecular machinery mediating active DNA demethylation in neurons and the potential functions of DNA demethylation in neuronal plasticity and mental disorders. We are using combinatory approaches to address these fundamental questions, including biochemistry, protein chip, RNA-seq, Bisulfite-seq, Chip-seq, electrophysiology and animal behavior.

Publications:

​Shin, J., Ming, G-l. and Song, H. (2014). Decoding neuronal transcriptomes and epigenomes via high-throughput sequencing. Nature Neuroscience (In press).
PubMed

Wen, W., Nguyen, H.N.N., Guo, Z., Lalli, M.A., Wang, X., Su, Y., Kim, N-S., Yoon, K.J., Shin, J., Zhang, C.,  Makri, G., Nauen, D., Yu, H., Guzman, E., Chiang, C-H., Yoritomo, N., Kaibuchi, K., Zou, J., Christian, K.M., Cheng, L., Ross, C.A., Margolis, R.L., Chen, G., Kosik, K.S., Song, H-j., and Ming, G-l. (2014). Synaptic dysregulation in a human iPSC model of major mental disorders. Nature (Epub ahead of print).
PubMed

Yoon, K.J., Nguyen, H.N., Ursini, G., Zhang, F., Kim, N-S., Wen, Z., Makri, G., Nauen, D., Shin, J.H., Park, Y., Chung, R., Pekle, E., Zhang, C., Towe, M., Hussaini S, M.Q., Lee, Y., Rujescu, D., St. Clair, D., Kleinman, J.E., Hyde, T.M., Krauss, G., Christian, K.M., Rapoport, J.L., Weinberger, D.R., Song, H-j., and Ming, G-l. (2014). Modeling a genetic risk for schizophrenia in iPSCs and mice reveals neural stem cell deficits associated with adherens junctions and polarity. Cell Stem Cell 15, 79-91.
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.
PubMed

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.
PubMed 

Jang, M.H., 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., Chiristian, 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.
PubMed

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.M., Ming, G.L.#, and Song, H.# (2012). Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature 489:150-4.
PubMed

Guo, J. U., Ma, D.K., Mo, H., Ball, M.P., Jang, M.H., Bonaguidi, M.A., Balazer, J.A. Eaves, H.L., Xie, B., Ford, E. Zhang, K., Ming, G-l., Gao, Y.#, and Song, H.# (2011). Neuronal activity modifies DNA methylation landscape in the adult brain. Nat. Neurosci. 14:1345-51.
PubMed

Bonaguidi, M.A., Wheeler, M.A., Shapiro, J.S., Stadel, R.P., Sun, G.J., Ming, G-l.#, and Song, H.# (2011). In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell 145, 1142-55. 
PubMed

Ming, G.L. and Song, H. (2011). Adult neurogenesis in the mammalian brain: Significant answers and significant questions. Neuron 70, 687-702.
PubMed

Guo, J.U., Su, Y., Zhong, C., Ming, G.L., and Song, H. (2011). Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145:423-34.
PubMed

Ma, D.K., Marchetto, M.C., Guo, J.U., Ming, G.L., Gage, F.H., and Song H. (2010). Epigenetic choreographers of neurogenesis in the adult mammalian brain. Nat Neurosci. 13:1338-44.
PubMed

Ma, D.K., Jang, M.H., Guo, J.U., Kitabatake, Y., Chang, M.L., Pow-Anpongkul, N., Flavell, R.A., Lu, B., Ming, G.L., Song, H. (2009). Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074-7.
PubMed

Duan, X., Chang, J., Ge, S-y., Faulkner, R., Liu, X-b., Kim, J.Y., Yang, C-h., Ma, D., Liu, C., Cheng, H.J., Ming, G-l., Lu, B. and Song, H-j. (2007). Disrupted-In-Schizophrenia 1 regulates integration of new neurons in the adult brain. Cell 13, 1146-58
PubMed

Ge, S., Goh, E.L., Sailor, K.A., Kitabatake, Y., Ming, G.L.#, Song, H.# (2006). GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439:589-93.
PubMed​

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