Last Updated August 5, 2008

Zhang Laboratory

Su Chun Zhang
Su Chun Zhang, MD, PhD

Research Goals & Interests

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 targets 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.



Relevant Publications

    1. Li XJ, Du ZW, Zarnowska ED, Pankratz M, Hansen LO, Pearce RA, Zhang S-C (2005): Specification of motoneurons from human embryonic stem cells.  Nature Biotechnology., 23: 215-221. 

    2. Yan Y, Yang, DL, Zarnowska ED, Du ZW, Valliere C, Pearce RA, Thomson JA, Zhang S-C (2005): Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells.  Stem Cells, 23: 781-790.

    3. Zhang, S-C (2006):  Neural subtype specification from embryonic stem cells.  Brain Pathology, 16: 132-142.

    4. Guillaume DJ, Johnson MA, Li XJ, Zhang S-C (2006):  Human ES cell-derived neural precursors develop into neurons and integrate into the host brain.  J. Neuroscience Research, 84: 1165-1176.

    5. Du ZW, Li XY, Nguyen, ND, O’ Bryan D, Zhang S-C (2006):  Induced Olig2 expression is sufficient for oligodendrocyte specification but not for motorneuron specification and astrocyte repression.  Molecular & Cellular Neuroscience, 33: 371-380. 

    6. Krencik R, Zhang S-C (2006):  Stem cell neural differentiation: a model for chemical biology.  Current Opinion in  Chemical Biology, 10: 592-597.

    7. Johnson M.A., Weick J., Pearce, R., Zhang S-C (2007):  Functional neural development of human embryonic stem cells: Accelerated synaptic activity via astrocyte co-culture.   Journal of Neuroscience, 27:3069-3077. 

    8. Pankratz MT, Li XJ, Lavaute TM, Lyons EA, Chen X, Zhang SC (2007) Directed neural differentiation of human embryonic stem cells via an obligated primitive anterior stage. Stem Cells 25: 1511-1520.

    9. Yang D, Zhang Z, Oldenburg M, Ayala M, Zhang S-C (2007):  Human ES cell-derived dopamine neurons reverse functional deficit in a Parkinson’s rat.  Stem Cells, in press (online, Oct 18, 2007).

    10. Xia X, Ayala M, Thiede BR, Zhang S-C (2007) In Vitro and In Vivo Induced Transgene Expression in Human Embryonic Stem Cells and Derivatives. Stem Cells, (Online, Nov 21, 2007).