The Zhang Laboratory
Faculty > Su-Chun Zhang
Su-Chun Zhang
Associate Professor, Anatomy and Neurology, Waisman Center
zhang@waisman.wisc.edu
Organ System/Disease Focus
Neural specification of embryonic stem cells
Aligned Research Focus
Nervous system—neural development, neurodegenerative diseases, basic stem cell science
Research Description
We intend to answer how functionally diversified neuronal and glial subtypes are born in the making of the 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 using special approaches. 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 and human biology.
By introducing disease-provoking genes into ESCs, 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 human ESCs in our laboratory are being tested for their therapeutic potential in animal models of neurological diseases. Our long-term goal is to translate this technology to the re-building of injured or diseased brains.
Selected References
Li XJ, Du ZW, Zarnowska ED, Pankratz M, Hansen LO, Pearce RA, Zhang S-C. Specification of motoneurons from human embryonic stem cells. Nature Biotechnol. 23:215-221. 2005.
Yan Y, Yang, DL, Zarnowska ED, Du ZW, Valliere C, Pearce RA, Thomson JA, Zhang S-C. Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23:781-790. 2005.
Zhang S-C. Neural subtype specification from embryonic stem cells. Brain Pathol. 16:132-142. 2006.
Johnson MA, Weick J, Pearce R, Zhang S-C. Functional neural development of human embryonic stem cells: Accelerated synaptic activity via astrocyte co-culture. J. Neurosci. 27:3069-3077. 2007.
Pankratz M, Li XJ, Chen X, Lyons E, Zhang S-C. Directed differentiation of regionally specified neural progenitors from human embryonic stem cells via an obligated primitive forebrain neuroectodermal stage. Stem Cells, 25:1511-1520. 2007.