MD, Wenzhou Medical College
PhD, University of Saskatchewan
Professor, Neuroscience and Neurology
Steenbock Professor of Behavioral & Neural Sciences
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.
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.
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.
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.
Chen Y, Xiong M, Zhang SC. (2015) Illuminating Parkinson's therapy with optogenetics. Nature Biotechnology. 33(2):149-50. doi: 10.1038/nbt.3140.
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.
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.
Liu H, Lu J, Chen H, Du Z, Li XJ, Zhang SC. (2015) Spinal muscular atrophy patient-derived motor neurons exhibit hyperexcitability. Science Reports. 20;5:12189. doi: 10.1038/srep12189.
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. 25;6:6626. doi: 10.1038/ncomms7626.
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.
Lu J, Bradley RA, Zhang SC. (2014) Turning reactive glia into functional neurons in the brain. Cell Stem Cell. 14(2):133-4.
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.
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.
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.
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.
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.
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.
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.