University of Wisconsin–Madison

Zhang Lab

Zhang Lab
Standing at center, Su-Chun Zhang, professor of neuroscience in the School of Medicine and Public Health, talks with postdoctoral student Lin Yao as she prepares stem-cell cultures in the Zhang’s research lab at the Waismam Center at the University of Wisconsin-Madison on March 8, 2013. (Photo by Jeff Miller/UW-Madison)

Su-Chun Zhang’s laboratory aims 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.

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 neural cells, including cortical glutamatergic neurons and GABA interneurons, striatal medium spiny GABAergic neurons, basal forebrain cholinergic neurons, midbrain dopamine neurons, spinal motoneurons, oligodendrocytes, and region-specific astrocyte subtypes. We are currently dissecting the transcriptional and epigenetic regulation of neuroectodermal induction and neural subtype specification.  Information learned from these studies sets up the foundation for us to switch, maintain, or re-program neural cell types.

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), Down syndrome and Alzheimer’s disease.  Using the state-of-the-art gene editing technology (TALENs, CRISPR) we have built transgenic disease human cell lines and corrected mutations in patient iPSCs. We are now dissecting cellular and molecular processes that underlie neural degeneration.  We are also transforming these cellular models to templates for drug discovery.

In the process of functional analysis of hPSC-derived neuronal and glial cells in animal models of neurological diseases, we discovered that appropriately specified neurons project to correct brain regions and connect to the right type of 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 are currently evaluating the therapeutic potential of human stem cell-generated midbrain dopamine neurons, striatal medium spiny GABA neurons, and spinal astrocytes in animal (including non-human primate) models of Parkinson’s disease, Huntington’s disease, and motor neuron diseases, respectively. To ensure safe and appropriate functional recovery, we have further built stem cells with functional switches.  With the understanding of the regulatory process of human neural specification and reprogramming, our long-term goal is to rebuild our aging or diseased brain from within.

Zhang Laboratory Staff:

Current:

  • Faculty:
    Su-Chun Zhang, MD, PhD, Professor of Neuroscience and Neurology
  • Administrative Assistant:
    Terry Tarrow
  • Senior Scientist:
    Zhong-Wei Du, PhD
  • Assistant Scientist:
    Jianfeng Lu, PhD
    Yuejun Chen, PhD
  • Research Associates:
    Jingyuan Cao, PhD (2011-)
    Andrew Petersen, PhD (2013-)
    Man Xiong, PhD (2013-)
    Yi Dong, PhD (2013-)
    Yuanlong Tao, PhD (2014-)
  • Senior Research Specialist:
    Melvin Ayala, BS
  • Graduate Students:
    Cindy Huang (CMB program, 2008-)
    Jeffery Jones (Molecular & Cellular Pharmacology, 2011-);  NSF fellowship.
    Robert Bradley (Cellular & Molecular Biology, 2012-)
    Joshua Knackert (Molecular & Cellular Pathology, 2013-)
  • Research Interns:
    Minna Oksanen

Previous fellows:

  • Yiping Yan (2001-2004)
    Current position: Senior scientist, Life Technology (Invitrogen), –2009.
  • Xue-Jun Li (2002-7)
    Current position: Asst Prof (tenure track), University of Connecticut Health Center, –2007
  • Daniel J. Guillaume (2002-2004)
    Current position: Assoc professor, Dept of Neurosurgery, Univ of Minnesota-2005.
  • Hilary Bennett (2002-2003)
    Current position: unknown (back to Canada)
  • Dali Yang (2004-2006)
    Current position: Lecturer at University of Rochester, NY –2006.
  • Zhi-Jian Zhang (2004-2008)
    Current position: Professor, Wuhan University, China –2008
  • Xiaofeng Xia (2004-2006)
    Current position:  Assistant Professor, Connell University (2006-)
  • Jason Meyer (2005-2007)
    Current position: Assistant Professor (Tenure Track) IUPUI, Indianapolis, IN –2011.
  • Jason Weick (2005-2012)
    Current position: Assistant Professor (tenure track), University of New Mexico, Albuquerque, NM–2012.
  • Baoyang Hu (2005-2010)
    Current position: Professor, Institute of Zoology, Chinese Academy of Science –2010
  • Xiaoqing Zhang (2007-2010)
    Current position:  Professor, Tongji University, Shanghai, China — 2010
  • Youndgong Yoo (2008-2010)
    Current position: Research Scientist, Seoul National University School of Medicine, Seoul, Korea — 2010
  • Danling Wang (2008)
    Current position: Postdoctoral fellow, Scripps Institute, CA.
  • Lixiang Ma (2008-2009)
    Current position: Associate prof, Fudan University Shanghai Medical School, Shanghai, China—2010
  • Wei Chen (2009-2010):
    Current position: Professor, Zhejiang University, Hangzhou, China–2010.
  • Kun Qian (2011-2012):
    Current position: Associate Professor, Huazhong University of Science and Technology, Wuhan, China
  • Hong Chen (2011-2014):
    Current position: Associate Professor, Huazhong University of Science and Technology, Wuhan, China
  • Lin Yao (2012—2014):
    Current position: Attending doctor, Second Military Medical University, Shanghai–2014

Past students:

  • Gina Piscitelli (MS-Neuroscience, 2001-2004)
    Current position:  Lecturer, Madison Area Technical College.
  • Matthew Pankratz (PhD-Neuroscience, 2002-2007)
    Current position:  postdoctoral fellow, Salk Institute, CA.
  • Daniel O’Bryan (MS-Cellular & Molecular Biology, 2002-2004)
    Current position: unknown.
  • Austin Johnson (MD/PhD-Neuroscience, 2003-2008)
    Current position: Resident in Colorado.
  • Timothy M. LaVaute (PhD-Neuroscience, 2003-2009)
    Current position:  Program officer, NINDS, NIH.
  • Robert Krencik (PhD-Neuroscience, 2005-2011)
    Current position: Postdoctoral fellow, UCSF, CA
  • Jiajie Xi (PhD, 2007-2012)
    Current position: Lecturer, Tongji University, Shanghai, China.