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Song-Hai Shi Ph.D.

Professor

1991-1996 Tsinghua University, China／B.S.

1996-2001 Cold Spring Harbor Laboratory & State University of New York at Stony Brook, USA／Ph.D.

2001-2006 University of California at San Francisco & Howard Hughes Medical Institute, USA／Postdoctoral Fellow

2006-2011 Memorial Sloan Kettering Cancer Center, USA／Assistant Member

2006-2011 Weill Cornell Medical College, USA／Assistant Professor

2011-2015 Memorial Sloan Kettering Cancer Center, USA／Associate Member／Member

2011-2015 Weill Cornell Medical College, USA／Associate Professor

2015-2019 Memorial Sloan Kettering Cancer Center, USA／Member

2015-2019 Weill Cornell Medical College, USA／Professor

2019-present Weill Cornell Medical College & Memorial Sloan Kettering Cancer Center, USA／Adjunct Professor & Member

2019-present School of Life Sciences & IDG/McGovern Institute for Brain Research at Tsinghua University／Professor & Director

Research interest

Development of the neocortex in the brain is considered to be the crowning achievement of evolution and likely holds the key to the superior mental prowess of humans. The ability of the neocortex to command all higher-order brain functions, such as sensory perception, language, conscious thought and reasoning, depends on the intricate circuitry comprised of a vast number of diverse neurons. Our research focuses on identifying the common commodities of neocortical circuits at both the structural and functional levels, and linking them with animal behaviors, with the ultimate goal of arriving at a circuit- and system-level understanding of neocortical operation and function under normal and disease conditions.

Selected publications

1. Dong, X., Zhang, Q., Yu, X., Wang, D., Ma, J., Ma, J., & Shi, S. H*. (2022). Metabolic lactate production coordinates vasculature development and progenitor behavior in the developing mouse neocortex. Nature neuroscience, 25(7), 865–875.

2. Lv, X., Li, S., Li, J., Yu, X. Y., Ge, X., Li, B., Hu, S., Lin, Y., Zhang, S., Yang, J., Zhang, X., Yan, J., Joyner, A. L., Shi, H., Wu, Q., & Shi, S. H. (2022). Patterned cPCDH expression regulates the fine organization of the neocortex. Nature, 612(7940), 503–511.

3. Ren, S.Q., Li, Z., Lin, S., Bergami, M., and Shi, S.-H. (2019) Precise long-range microcircuit-to-microcircuit communication connects the frontal and sensory cortices in the mammalian brain. Neuron.104, 1-17. (PMID: 31371111)

4. Lv X., Ren, S.-Q., Zhang, X.-J., Shen Z., Ghosh, T., Xianyu, A., Gao, P., Li, Z., Lin, S., Yu, Y., Zhang, Q., Groszer, M., and Shi, S.-H. (2019) TBR2 coordinates neurogenesis expansion and precise microcircuit organization via Protocadherin 19 in the mammalian cortex. Nat. Commun. 10(1):3946. (PMCID: PMC6718393)

5. Sultan, K.T., Liu, W.A., Li, Z.-L., Shen, Z., Li, Z., Zhang X.-J., Dean, O., Ma, J., and Shi, S.-H. (2018) Progressive divisions of Mmultipotent neural progenitors generate late-born chandelier cells in the neocortex. Nat. Commun. 9: 4595. (PMCID: PMC6214958)

6. Liu, W.-A., Chen, S., Li, Z., Lee, C.,-H., Mirzaa, G., Dobyns, W.B., Ross, M.E., Zhang, J., and Shi, S.-H. (2018) PARD3 dysfunction in conjunction with dynamic HIPPO signaling drives cortical enlargement with massive heterotopia. Genes & Dev. 32: 763-780. (PMCID: PMC6049519)

7. Zhang, X.-J., Li, Z., Han, Z., Sultan, K.T., Huang, K., and Shi, S.-H. (2017) Precise inhibitory microcircuit assembly of developmentally related neocortical interneurons in clusters. Nat. Commun. 8:16091. (PMCID: PMC5511369)

8. Shi, W., Xianyu, A., Han, Z., Tang, X., Li, Z., Zhong, H., Mao, T., Huang, K., and Shi, S.-H. (2017) Ontogenetic establishment of order-specific nuclear organization in the mammalian thalamus. Nat. Neurosci. 20: 516-528 (PMCID: PMC5374008)

9. Qi, Y., Zhang, X.-J., Renier, N., Wu, Z., Atkin, T., Sun, Z., Ozair, M.Z., Tchieu, J., Zimmer, B., Fattahi, F., Ganat, Y., Azevedo, R., Zeltner, N., Brivanlou, A.H., Karayiorgou, M., Gogos, J., Tomishima, M., Tessier-Lavigne, M., Shi, S.-H., and Studer, L. (2017) Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells. Nat. Biotechnol. 35:154-163. (PMCID: PMC5516899)

10. Sultan, K.T.^*, Han, Z.^*, Zhang, X.-J.^*, Xianyu, A., Li, Z., Huang, K., and Shi, S.-H. (2016) Clonally related GABAergic interneurons do not randomly disperse but frequently form local clusters in the forebrain. (^* Co-first author) Neuron 92: 31-44. (PMCID: PMC5066572)

11. Tan, X., Liu, W.A., Zhang, X.-J., Shi, W., Ren, S.-Q., Li, Z., Brown, K.N., and Shi, S.-H. (2016) Vascular regulation of ventral telencephalic progenitors and neocortical interneuron production. Dev. Cell 36:624-638. (PMCID: PMC4806403)

12. He, S., Li, Z., Ge, S., Yu, Y.-C., and Shi, S.-H. (2015) Inside-out radial migration facilitates lineage-dependent microcircuit assembly in the neocortex. Neuron 86: 1159-1166. (PMCID: PMC4458701)

13. Gao, P., Postiglione Pia, M., Krieger, T.G., Hernandez, L., T., Wang, C., Han, Z., Streicher, C., Papusheva, E., Insolera, R., Chugh, K., Kodish, O., Huang, K., Simons, B.D., Luo, L., Hippenmeyer, S., and Shi, S.-H. (2014) Deterministic progenitor behavior and unitary production of neurons in the neocortex. Cell 159:775-788. (PMCID: PMC4225456)

14. Insolera, R., Bazzi, H., W. Shao, Anderson, K.V., and Shi, S.-H. (2014) Cortical neurogenesis in the absence of centrioles. Nat. Neurosci. 17:1528-1535. (PMCID: PMC4213237)

15. Insolera, R., Shao, W., Airik, R., Hildebrandt, F., and Shi, S.-H. (2014) SDCCAG8 regulates pericentriolar material recruitment and neuronal migration in the developing neocortex. Neuron 83: 805-822. (PMCID: PMC4141904)

16. Xu, H.-T., Han Z., Gao, P., He, S., Li, Z., Shi, W., Kordish, O., Shao, W., Brown, K.N., Huang, K., and Shi. S-H. (2014) Lineage-dependent structural and functional organization of the hippocampus. Cell 157: 1552-1564. (PMCID: PMC4120073)

17. Chen, S., Chen, J., Shi, H., Wei, M., Castaneda-Castellanos, D.R., Pei, X., Kriegstein, A.R., Zhang M.-J., and Shi, S.-H. (2013) Regulation of microtubule stability and organization by mammalian Par3 in specifying neuronal polarity. Dev. Cell 24: 26-40. (PMCID: PMC3375857)

18. Li, Y., Lu, H., Cheng, P.-l., Ge, S., Xu, H., Shi, S.-H., and Dan, Y. (2012) Clonally related visual cortical neurons show similar stimulus feature selectivity. Nature 486:118-21. (PMCID: PMC3375857)

19. Yu, Y.-C., He, S., Chen, S., Fu, Y., Brown, K.N., Yao, X.H., Ma, J., Gao, K.P., Sosinsky, G.E., Huang, K., and Shi, S.-H. (2012) Preferential electric coupling regulates neocortical lineage-dependent microcircuit assembly. Nature 486:113-7. (PMCID: PMC3599787)

20. Brown, K.N., Chen, S., Han, Z., Lu, C.-H., Tan, X., Ding, L., Zhang, X.-J., Cruz, A. L., Saur, D., Anderson, S.A., Huang, K., and Shi, S.-H. (2011) Clonal Production and Organization of Inhibitory Interneurons in the Neocortex. Science 334: 480-486. (PMCID: PMC3304494)

21. Wang, X., Tsai, J.-W., Imai, J.H., Lin, W.-N., Valle, R.B., and Shi, S.-H. (2009) Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature 461: 947-955. (PMCID: PMC2764320)

22. Bultje, R.S., Castaneda-Castellanos, D.R., Jan, L.Y., Jan, Y.N., Kriegstein, A.R., and Shi, S.-H. (2009) Mammalian Par3 regulates progenitor cell asymmetric division via Notch signaling in the developing neocortex. Neuron 63: 189-202. (PMCID: PMC2736606)

23. Yu, Y.-C., Bultje, R.S., Wang, X., and Shi, S.-H. (2009) Specific synapses develop preferentially among sister excitatory neurons in the neocortex. Nature 458: 501-504. (PMCID: PMC2727717)

24. Huang, C.S.*, Shi, S.-H.*, Ule, J., Ruggiu, M., Barker, L.A., Darnell, R.B., Jan, Y.N., and Jan, L.Y. (2005). Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition. Cell 123:105-118 (* contributed equally). (PMID: 16213216)

25. Shi, S.-H., Cheng, T., Jan, L.Y., and Jan, Y.N. (2004). The immunoglobulin family member dendrite arborization and synapse maturation 1 (Dasm1) controls excitatory synapse maturation. Proc. Natl. Acad. Sci. USA 101:13346-13351. (PMCID: PMC516569)

26. Shi, S.-H., Cox, D.N., Wang, D., Jan, L.Y., and Jan, Y.N. (2004). Control of dendrite arborization by an Ig family member, dendrite arborization and synapse maturation 1 (Dasm1). Proc. Natl. Acad. Sci. USA 101:13341-13345. (PMID: 15340157)

27. Shi, S.-H., Jan, L.Y., and Jan, Y.-N. (2003). Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell 112:63-75. (PMID: 12526794)

28. Shi, S.-H., Hayashi, Y., Esteban, J.A., and Malinow, R. (2001). Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell 105:331-343. (PMID: 11348590)

29. Hayashi, Y. *, Shi, S.-H. *, Esteban, J.A., Piccini, A., Poncer, J.-C., and Malinow, R. (2000). Driving AMPA receptors into synapses by LTP or CaMKII: Requirement for GluR1 and PDZ domain interaction. Science 287:2262-2267 (* contributed equally). (PMID: 10731148)

30. Shi, S.-H., Hayashi, Y., Petralia, R.S., Zaman, S.H., Wenthold, R.J., Svoboda, K., and Malinow, R. (1999). Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284:1811-1816. (PMID: 10364548)

Awards

Runner-up, Breakthrough of the Year, Science (1999)

Amersham Biosciences and Science Prize for Young Scientists, Grand Prize (2001)

Helen Hay Whitney Foundation Fellowship (2002-2005)

Klingenstein Award (2007)

NARSAD Young Investigator Award (2008)

McKnight Scholar Award (2010)

Blavatnik Awards for Young Scientists (2010)

The Vilcek Prize for Creative Promise in Biomedical Science, Finalist (2012)

Howard Hughes Medical Institute (HHMI) Faculty Scholar Award (2016)

Contact information

Tel: 010-62791995

E-mail：shisonghai@mail.tsinghua.edu.cn

web：http://shis-lab.life.tsinghua.edu.cn/#/home