Su-Chun Zhang, MD, PHD

Pubmed

News Releases:

• Stem Cell Transplant Treats Parkinson’s Disease in Monkeys, 2022
• Pioneering research brings potential Parkinson’s disease treatment one step closer, 2022
• Stem cell project to create new model to study brain development and Down syndrome, 2021
• Individualized brain cell grafts reverse Parkinson’s symptoms in monkeys, 2021
• Stem cells can repair Parkinson’s-damaged circuits in mouse brains, 2020
• Cell transplant treats Parkinson’s in mice under control of designer drug. 28 April 2016
• First serotonin neurons made from human stem cells, 14 December 2015
• Stem cell research shows promise of memory restoration; 9 July 2013
• Down syndrome neurons grown from stem cells show signature problems; 27 May 2013
• Adult cells transformed into early-stage nerve cells, bypassing the pluripotent stem cell stage; 2 May 2013
• Stem cell transplant restores memory, learning in mice; 21 April 2013
• Stem cells hint at potential treatment for Huntington’s disease; 15 March 2012
• Human brain’s most ubiquitous cell cultivated in lab dish; 22 May 2011
• Gene regulating human brain development identified; 1 July 2010

More information:

• Zhang Laboratory Home Page

Research Description:

Our laboratory focuses on addressing how functionally diversified neuronal and glial subtypes are born in the building and rebuilding of our human brain. We have developed models of neural differentiation from mouse, monkey, and human pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). By following the developmental principles, we have successfully directed hPSCs to regionally and functionally specialized neuronal and glial subtypes. We are currently dissecting the transcriptional and epigenetic regulation of the self-renewal of neural progenitors.  Information learned from these studies sets up the foundation for us to switch, maintain, or re-program neural cell types. These cell types also form the building blocks for printing neural tissues by design, enabling us to decode the intricate circuits in our human brain.

Building upon our success in directed neural differentiation, we are establishing iPSCs and reprogramming neural cells from skin tissues or blood cells of patients with neurological disorders, focusing on motor neuron diseases (ALS, SMA), Alexander disease, Down syndrome, Parkinson’s disease and Alzheimer’s disease.  Using the state-of-the-art genome editing technology (CRISPR) we have built transgenic disease human cell lines and corrected mutations in patient iPSCs. We are now engineering cells to manifest disease-relevant phenotypes that normally occur decades in life so that the cellular and molecular underpinning of neural degeneration may be dissected.  We are also transforming these cellular models to templates for drug discovery.

We have discovered that appropriately specified neurons project to correct brain regions and connect to the right target neurons in the adult mouse brain, suggesting a surprisingly regenerative capacity of human stem cell-produced neurons, very much like those born during embryonic development.  We have also found that the transplanted human neurons receive appropriate inputs, a process largely dependent on the cell identity. We are currently evaluating the therapeutic potential of human stem cell-generated neural subtypes in animal (including non-human primate) models of Parkinson’s disease, stroke, and spinal cord injury. In particular, we have shown that cell therapy for Parkinson’s disease is safe and effective in a nonhuman primate model. We are now in the process applying for FDA approval for clinical trial for cell therapy for Parkinosn’s disease.

Selected References:

• Fathi A, Mathivanan S, Kong L, Petersen AJ, Harder CRK, Block J, Miller JM, Bhattacharyya A, Wang D, Zhang SC. Chemically induced senescence in human stem cell-derived neurons promotes phenotypic presentation of neurodegeneration. Aging Cell. 2022 Jan;21(1): e13541. doi: 10.1111/acel.13541. Epub 2021 Dec 24. PubMed PMID: 34953016; PubMed Central PMCID: PMC8761019.
• Tao Y, Vermilyea SC, Zammit M, Lu J, Olsen M, Metzger JM, Yao L, Chen Y, Phillips S, Holden JE, Bondarenko V, Block WF, Barnhart TE, Schultz-Darken N, Brunner K, Simmons H, Christian BT, Emborg ME, Zhang SC. Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys. Nat Med. 2021 Apr;27(4):632-639. doi: 10.1038/s41591-021-01257-1. Epub 2021 Mar 1. PubMed PMID: 33649496; PubMed Central PMCID: PMC8198752.
• Gong C, Zheng X, Guo F, Wang Y, Zhang S, Chen J, Sun X, Shah SZA, Zheng Y, Li X, Yin Y, Li Q, Huang X, Guo T, Han X, Zhang SC, Wang W, Chen H. Human spinal GABA neurons alleviate spasticity and improve locomotion in rats with spinal cord injury. Cell Rep. 2021 Mar 23;34(12):108889. doi: 10.1016/j.celrep.2021.108889. PubMed PMID: 33761348.
  Xiong M, Tao Y, Gao Q, Feng B, Yan W, Zhou Y, Kotsonis TA, Yuan T, You Z, Wu Z, Xi J, Haberman A, Graham J, Block J, Zhou W, Chen Y, Zhang SC. Human Stem Cell-Derived Neurons Repair Circuits and Restore Neural Function. Cell Stem Cell. 2021 Jan 7;28(1):112-126.e6. doi: 10.1016/j.stem.2020.08.014. Epub 2020 Sep 22. PubMed PMID: 32966778; PubMed Central PMCID: PMC7796915.
• Mou Y, Dong Y, Chen Z, Denton KR, Duff MO, Blackstone C, Zhang SC, Li XJ. Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia. Acta Neuropathol Commun. 2020 Dec 7;8(1):214. doi: 10.1186/s40478-020-01088-0. PubMed PMID: 33287888; PubMed Central PMCID: PMC7720406.
• Tao Y, Cao J, Li M, Hoffmann B, Xu K, Chen J, Lu X, Guo F, Li X, Phillips MJ, Gamm DM, Chen H, Zhang SC. PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm. EMBO Rep. 2020 Sep 3;21(9): e50000. doi: 10.15252/embr.202050000. Epub 2020 Jul 23. PubMed PMID: 32700445; PubMed Central PMCID: PMC7507545.
• Dong Y, Xiong M, Chen Y, Tao Y, Li X, Bhattacharyya A, Zhang SC. Plasticity of Synaptic Transmission in Human Stem Cell-Derived Neural Networks. iScience. 2020 Feb 21;23(2):100829. doi: 10.1016/j.isci.2020.100829. Epub 2020 Jan 9. PubMed PMID: 31981924; PubMed Central PMCID: PMC6993006.
• 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. Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties. Development. 2019 Jul 8;146(13). doi: 10.1242/dev.170910. PubMed PMID: 31189664; PubMed Central PMCID: PMC6633609.