Su-Chun Zhang, MD, PhD

Position title: Professor, Neuroscience and Neurology

MD, Wenzhou Medical College
PhD, University of Saskatchewan
Steenbock Professor of Behavioral & Neural Sciences

Contact Information

T613 Waisman Center
1500 Highland Avenue
Madison, WI 53705
608.265.2543
zhang@waisman.wisc.edu
Lab Website: Zhang Lab, Stem Cell Research Program

Research Statement

Our laboratory intends to answer how functionally diversified neuronal and glial subtypes are born in the making of our human brain. We have developed models of neural differentiation from mouse, monkey, and human embryonic stem cells (ESCs) that recapitulate key events occurring during early embryo development, including induction of multipotential neuroepithelial cells that form neural tube-like structures, patterning of region-specific neural progenitors, and generation of neurons and glia with particular transmitter or functional phenotypes. In parallel, we are building transgenic human ESC lines with regulatable gene expression. Together, we are dissecting biochemical interactions underlying the cellular differentiation processes under defined conditions. Such studies will hopefully bridge what we have learned from animal studies to human biology.

By introducing disease-provoking genes into ESCs or by activating the pluoripotent state of genetically mutated adult cells, we are creating model systems in which pathological cellular and molecular processes may be analyzed in bona fide human neurons and glia in a simplified environment. Such systems may be transformed to emplates for pharmaceutical screening.

The specialized neural cells produced from normal human ESCs in our laboratory are being tested for their therapeutic potential in animal models of neurological diseases such as Parkinson?s disease, amyotrophic lateral sclerosis, spinal cord injury, and multiple sclerosis. Our long-term goal is to translate this technology to the re-building of our injured or diseased brain.

Selected Publications

Giffin-Rao, Y., Sheng, J., Strand, B., Xu, K., Huang, L., Medo, M., Risgaard, K. A., Dantinne, S., Mohan, S., Keshan, A., Daley, R. A., Jr, Levesque, B., Amundson, L., Reese, R., Sousa, A., Tao, Y., Wang, D., Zhang, S. C., & Bhattacharyya, A. (2022). Altered patterning of trisomy 21 interneuron progenitors. Stem cell reports, 17(6), 1366–1379. https://doi.org/10.1016/j.stemcr.2022.05.001
Rahimpour, S., Zhang, S. C., Vitek, J. L., Mitchell, K. T., & Turner, D. A. (2022). Comparative efficacy of surgical approaches to disease modification in Parkinson disease. NPJ Parkinson’s disease, 8(1), 33. https://doi.org/10.1038/s41531-022-00296-w
Wang, L., Bukhari, H., Kong, L., Hagemann, T. L., Zhang, S. C., Messing, A., & Feany, M. B. (2022). Anastasis Drives Senescence and Non-Cell Autonomous Neurodegeneration in the Astrogliopathy Alexander Disease. The Journal of neuroscience : the official journal of the Society for Neuroscience, 42(12), 2584–2597. https://doi.org/10.1523/JNEUROSCI.1659-21.2021
Fathi, A., Mathivanan, S., Kong, L., Petersen, A. J., Harder, C., Block, J., Miller, J. M., Bhattacharyya, A., Wang, D., & Zhang, S. C. (2022). Chemically induced senescence in human stem cell-derived neurons promotes phenotypic presentation of neurodegeneration. Aging cell, 21(1), e13541. https://doi.org/10.1111/acel.13541
Gong, C., Zheng, X., Guo, F., Wang, Y., Zhang, S., Chen, J., Sun, X., Shah, S., Zheng, Y., Li, X., Yin, Y., Li, Q., Huang, X., Guo, T., Han, X., Zhang, S. C., Wang, W., & Chen, H. (2021). Human spinal GABA neurons alleviate spasticity and improve locomotion in rats with spinal cord injury. Cell reports, 34(12), 108889. https://doi.org/10.1016/j.celrep.2021.108889
Xiong, M., Tao, Y., Gao, Q., Feng, B., Yan, W., Zhou, Y., Kotsonis, T. A., Yuan, T., You, Z., Wu, Z., Xi, J., Haberman, A., Graham, J., Block, J., Zhou, W., Chen, Y., & Zhang, S. C. (2021). Human Stem Cell-Derived Neurons Repair Circuits and Restore Neural Function. Cell stem cell, 28(1), 112–126.e6. https://doi.org/10.1016/j.stem.2020.08.014
Mou, Y., Dong, Y., Chen, Z., Denton, K. R., Duff, M. O., Blackstone, C., Zhang, S. C., & Li, X. J. (2020). Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia. Acta neuropathologica communications, 8(1), 214. https://doi.org/10.1186/s40478-020-01088-0
Tao, Y., Cao, J., Li, M., Hoffmann, B., Xu, K., Chen, J., Lu, X., Guo, F., Li, X., Phillips, M. J., Gamm, D. M., Chen, H., & Zhang, S. C. (2020). PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm. EMBO reports, 21(9), e50000. https://doi.org/10.15252/embr.202050000
Dong, Y., Xiong, M., Chen, Y., Tao, Y., Li, X., Bhattacharyya, A., & Zhang, S. C. (2020). Plasticity of Synaptic Transmission in Human Stem Cell-Derived Neural Networks. iScience, 23(2), 100829. https://doi.org/10.1016/j.isci.2020.100829
Bradley RA, Shireman J, McFalls C, Choi J, Canfield SG, Dong Y, Liu K, Lisota B, Jones JR, Petersen A, Bhattacharyya A, Palecek SP, Shusta EV, Kendziorski C, Zhang SC. (2019). Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties. Development, 8;146(13):dev170910. doi: 10.1242/dev.170910.
Yin, Y., Petersen, A. J., Soref, C., Richards, W. D., Ludwig, T., Taapken, S., Berndt, E., Zhang, S. C., & Bhattacharyya, A. (2019). Generation of seven induced pluripotent stem cell lines from neonates of different ethnic backgrounds. Stem cell research, 34, 101365. https://doi.org/10.1016/j.scr.2018.101365
Upadhya D, Hattiangady B, Castro OW, Shuai B, Kodali M, Attaluri S, Bates A, Dong Y, Zhang SC, Prockop DJ, Shetty AK. (2019). Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration. PNAS USA, 116(1):287-296. doi: 10.1073/pnas.1814185115.
Jones JR, Kong L, Hanna MG 4th, Hoffman B, Krencik R, Bradley R, Hagemann T, Choi J, Doers M, Dubovis M, Sherafat MA, Bhattacharyya A, Kendziorski C, Audhya A, Messing A, Zhang SC. (2018). Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes. Cell Reports, 25(4):947-958.e4. doi: 10.1016/j.celrep.2018.09.083.
Wang, L., Xia, J., Li, J., Hagemann, T. L., Jones, J. R., Fraenkel, E., Weitz, D. A., Zhang, S. C., Messing, A., & Feany, M. B. (2018). Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease. Nature communications, 9(1), 1899. https://doi.org/10.1038/s41467-018-04269-7
Huo HQ, Qu ZY, Yuan F, Ma L, Yao L, Xu M, Hu Y, Ji J, Bhattacharyya A, Zhang SC, Liu Y. (2018). Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons. Stem Cell Reports, 10;10(4):1251-1266.
Tyzack GE, Hall CE, Sibley CR, Cymes T, Forostyak S, Carlino G, Meyer IF, Schiavo G, Zhang SC, Gibbons GM, Newcombe J, Patani R, Lakatos A. (2017). A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models. Nature Communications. 8(1):1164. doi: 10.1038/s41467-017-01283-z.
Oksanen M, Petersen AJ, Naumenko N, Puttonen K, Lehtonen Š, Gubert Olivé M, Shakirzyanova A, Leskelä S, Sarajärvi T, Viitanen M, Rinne JO, Hiltunen M, Haapasalo A, Giniatullin R, Tavi P, Zhang SC, Kanninen KM, Hämäläinen RH, Koistinaho J. (2017). PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer’s Disease. Stem Cell Reports, 9(6):1885-1897. doi: 10.1016/j.stemcr.2017.10.016.
Alisch RS, Van Hulle C, Chopra P, Bhattacharyya A, Zhang SC, Davidson RJ, Kalin NH, Goldsmith HH. (2017). A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals susceptibility loci in humans. Translational Psychiatry, 7(12):1282. PMCID: PMC5802687. DOI: 10.1038/s41398-017-0047-9
Qian K, Huang H, Peterson A, Hu B, Maragakis NJ, Ming GL, Chen H, Zhang SC. (2017). Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo. Stem Cell Reports. 8(4):843-855. doi: 10.1016/j.stemcr.2017.03.003.
Tao Y, Zhang SC. (2016) Neural Subtype Specification from Human Pluripotent Stem Cells. Cell Stem Cell. 19(5):573-586. doi: 10.1016/j.stem.2016.10.015.
Zhong X, Hao L, Lu J, Ye H, Zhang SC, Li L. (2016) Quantitative analysis of serotonin secreted by human embryonic stem cells-derived serotonergic neurons via pH-mediated online stacking-CE-ESI-MRM. Electrophoresis. 37(7-8):1027-30. doi: 10.1002/elps.201500496.
Lu J, Zhong X, Liu H, Hao L, Huang CT, Sherafat MA, Jones J, Ayala M, Li L, Zhang SC. (2016) Generation of serotonin neurons from human pluripotent stem cells. Nature Biotechnology. 34(1):89-94. doi: 10.1038/nbt.3435.
Chen Y, Xiong M, Zhang SC. (2015) Illuminating Parkinson’s therapy with optogenetics. Nature Biotechnology. 33(2):149-50. doi: 10.1038/nbt.3140.
Chen Y, Cao J, Xiong M, Petersen AJ, Dong Y, Tao Y, Huang CT, Du Z, Zhang SC. (2015) Engineering Human Stem Cell Lines with Inducible Gene Knockout using CRISPR/Cas9. Cell Stem Cell. 6;17(2):233-44. doi: 10.1016/j.stem.2015.06.001.
Hoeber J, Trolle C, Konig N, Du Z, Gallo A, Hermans E, Aldskogius H, Shortland P, Zhang SC, Deumens R, Kozlova EN. (2015) Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury. Scientific Reports. 8;5:10666. doi: 10.1038/srep10666.
Liu H, Lu J, Chen H, Du Z, Li XJ, Zhang SC. (2015) Spinal muscular atrophy patient-derived motor neurons exhibit hyperexcitability. Science Reports, 5:12189. doi: 10.1038/srep12189.
Li M, Pehar M, Liu Y, Bhattacharyya A, Zhang SC, O’Riordan KJ, Burger C, D’Adamio L, Puglielli L. (2015) The amyloid precursor protein (APP) intracellular domain regulates translation of p44, a short isoform of p53, through an IRES-dependent mechanism. Neurobiology of Aging. 36(10):2725-36. doi: 10.1016/j.neurobiolaging.
Du ZW, Chen H, Liu H, Lu J, Qian K, Huang CL, Zhong X, Fan F, Zhang SC. (2015) Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells. Nature Communications, 6:6626. doi: 10.1038/ncomms7626.
Chen H, Qian K, Du Z, Cao J, Petersen A, Liu H, Blackbourn LW 4th, Huang CL, Errigo A, Yin Y, Lu J, Ayala M, Zhang SC. (2014) Modeling ALS with iPSCs reveals that mutant SOD1 misregulates neurofilament balance in motor neurons. Cell Stem Cell. 14(6):796-809.
Lu J, Bradley RA, Zhang SC. (2014) Turning reactive glia into functional neurons in the brain. Cell Stem Cell. 14(2):133-4.
Qian K, Huang CL, Chen H, Blackbourn LW 4th, Chen Y, Cao J, Yao L, Sauvey C, Du Z, Zhang SC. (2014) A simple and efficient system for regulating gene expression in human pluripotent stem cells and derivatives. Stem Cells. 32(5):1230-8.
Williams EC, Zhong X, Mohamed A, Li R, Liu Y, Dong Q, Ananiev GE, Mok JC, Lin BR, Lu J, Chiao C, Cherney R, Li H, Zhang SC, Chang Q. (2014) Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons. Human Molecular Genetics. 23(11):2968-80.
Doers ME, Musser MT, Nichol R, Berndt ER, Baker M, Gomez TM, Zhang SC, Abbeduto L, Bhattacharyya A. (2014) iPSC-derived forebrain neurons from FXS individuals show defects in initial neurite outgrowth. Stem Cells and Development. 1;23(15):1777-87.
Jensen MB, Yan H, Krishnaney-Davison R, Al Sawaf A, Zhang SC. (2013) Survival and Differentiation of Transplanted Neural Stem Cells Derived from Human Induced Pluripotent Stem Cells in A Rat Stroke Model. Journal of Stroke and Cerebrovascular Diseases. 22(4):304-8.
Lu J, Liu H, Huang CT, Chen H, Du Z, Liu Y, Sherafat MA, Zhang SC. (2013) Generation of integration-free and region-specific neural progenitors from primate fibroblasts. Cell Reports. 30;3(5):1580-91.
Du ZW, Ma LX, Phillips C, Zhang SC. (2013) miR-200 and miR-96 families repress neural induction from human embryonic stem cells. Development. 140(12):2611-8.
Emborg ME, Zhang Z, Joers V, Brunner K, Bondarenko V, Ohshima S, Zhang SC. (2013) Intracerebral transplantation of differentiated human embryonic stem cells to hemiparkinsonian monkeys. Cell Transplantation. 22(5):831-8.
Liu Y, Weick JP, Liu H, Krencik R, Zhang X, Ma L, Zhou GM, Ayala M, Zhang SC. (2013) Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits. Nature Biotechnology. 31(5):440-7.
Emborg ME, Liu Y, Xi J, Zhang X, Yin Y, Lu J, Joers V, Swanson C, Holden JE, Zhang SC. (2013) Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain. Cell Reports. 28;3(3):646-50.
Liu Y, Liu H, Sauvey C, Yao L, Zarnowska ED, Zhang SC. (2013) Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nature Protocols. 8(9):1670-9.
Weick JP, Held DL, Bonadurer GF 3rd, Doers ME, Liu Y, Maguire C, Clark A, Knackert JA, Molinarolo K, Musser M, Yao L, Yin Y, Lu J, Zhang X, Zhang SC, Bhattacharyya A. (2013) Deficits in human trisomy 21 iPSCs and neurons. Proceedings of the National Academy of Sciences of the United States. 110(24):9962-7.
Ma L, Hu B, Liu Y, Vermilyea SC, Liu H, Gao L, Sun Y, Zhang X, Zhang SC. (2012) Human Embryonic Stem Cell-Derived GABA Neurons Correct Locomotion Deficits in Quinolinic Acid-Lesioned Mice. Cell Stem Cell. Mar 15.
Weick JP, Liu Y, Zhang SC. (2011) Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network. Proceedings of the National Academy of Sciences of the United States of America. Dec 13;108(50):20189-94.
Krencik R, Weick JP, Liu Y, Zhang ZJ, Zhang SC. (2011) Specification of transplantable astroglial subtypes from human pluripotent stem cells. Nature Biotechnology. May 22;29(6):528-34.
Weick JP, Johnson MA, Skroch SP, Williams JC, Deisseroth K, Zhang SC. (2010) Functional control of transplantable human ESC-derived neurons via optogenetic targeting. Stem Cells. Nov;28(11):2008-16 PMCID: PMC2988875.
Hu BY, Weick JP, Yu J, Ma LX, Zhang XQ, Thomson JA, Zhang SC. (2010) Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proceedings of the National Academy of Sciences of the United States of America. Mar 2;107(9):4335-40.