Ping Wu, M.D., Ph.D.

John S. Dunn Distinguished Chair in Neurological Recovery
Professor

  • Affiliations:
    Department of Neuroscience & Cell Biology
    TIRR Mission Connect
    George P. and Cynthia Woods Mitchell Center for Neurodegenerative Diseases
    Moody Center for Traumatic Brain & Spinal Cord Injury Research
    Center for Addiction Research
  • Route: 0620 4.212B Research Building 17
  • Tel: (409) 772-9858
  • Fax: (409) 747-2200
  • piwu@utmb.edu
  • Wu Lab Webpage
  • Dr. Wu's Publications
  • Wu CV

Ping Wu, M.D., Ph.D.

Education

• Bachelor of Medicine (equivalent to Doctor of Medicine), Peking University, 1984
• Doctor of Philosophy, University of Texas Medical Branch, 1991
• Post-Doctoral Training, University of Florida College of Medicine, 1991-1994
• Instructor, Harvard School of Medicine, 1994-1998

About the Lab

My laboratory is studying human neural stem cells and currently focuses on understanding the molecular mechanisms of self-renewal, plasticity, multipotential and trophic factor secretion of stem cells. The outcome of our studies will provide insights towards development of stem cell-related therapy to treat diseases like ALS (Lou Gehrig’s disease), traumatic brain and spinal cord injury.

Human neural stem cells can be used to study how the human nervous system is developed, how neural diseases damage the system and how to use stem cells to repair the injured or degenerated brain and spinal cord.  Previously, our group has developed an in vitro priming technique, which allowed us to obtain a large proportion of transplanted stem cells becoming cholinergic nerve cells in rat spinal cord and brain. We further showed that stem cell-derived motor nerve cells, when grafted, sent projections to reach muscle targets, and stem cell grafts improved motor function in rat models with acute and chronic spinal cord injury. Using a brain injury model, we also found that stem cell grafts prevented injury-induced cognitive impairment (memory loss) by secreting trophic factors to protect injured nerve cells. Next, we will focus on the molecular and cellular mechanisms underlying stem cell priming and differentiation as well as interactions between stem cells and host cells. Such studies will allow us to improve the efficacy of stem cell therapy for various neurological disorders, including spinal cord injury, brain trauma and Lou Gehrig’s disease (amyotrophic lateral sclerosis or ALS).

  • Proliferation of human fetal neural stem cells.

We successfully expanded human neural stem cells (hNSCs) derived from discarded human fetal brains for more than 96 passages (over 3 years) in vitro. hNSCs are grown as neurospheres in media containing basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and leukemia inhibitor factor (LIF). The long-term expanded hNSCs show normal diploid karyotype, similar growth rate and capability to differentiate into all three neural lineages (neurons, astroglia and oligodendrocytes).

  • Priming and differentiation of human neural stem cells.

We developed an in vitro priming procedure, bFGF plus heparin and laminin for 4-5 days. Such priming is crucial to guide hNSCs to becompetent to become cholinergic motor neurons after withdrawal of bFGF and allowed for further differentiation in vitro.  

  • Grafting human neural stem cells into acute and chronic injured rodent spinal cords.

Many primed hNSCs acquire a motor neuron phenotype after transplanted into intact and contusion-injured rat spinal cords. In a sciatic axotomy animal model, we showed for the first time that grafted hNSC-derived motor neurons sent axons through ventral root and sciatic nerve, and reach gastrocnemius by forming neuromuscular junctions. Such hNSC grafts replaced lost motor neurons and improved nerve conductivity and motor function.

 

  • Grafting human neural stem cells into traumatically injured rodent brains.

We discovered that implanting hNSCs into hippocampus 24 hr after fluid percussion traumatic brain injury significantly improved cognitive function as determined by Morris Water Maze tests. Such functional effects of the grafts are most likely due to the neurotrophic factors, including glial cell-derived neurotrophic factor (GDNF), secreted from hNSCs. Further studies are underway to confirm the role of GDNF and elucidate further the underlying cellular and molecular mechanisms.

  • Interaction of human neural stem cells and non-neural glial cells.

Grafted hNSCs and their progenies apparently interact with host cells. We have shown that normal astroglia supported long-term survival of hNSC-derived cholinergic neurons in vitro. However, preliminary studies also indicated that injured or degenerative neural environment adversely affected grafted hNSCs. One of our current research focuses is to determine the cross-talk between hNSCs and microglia/astroglia, as well as molecular mechanisms underlying glial effects on differentiation, maturation and survival of hNSC-derived neurons.

Selected Publications

Wang E, Gao J, Denner L, Dunn T, Parles M, Zhang L and Wu P, 2012, Molecular mechanisms underlying protective effects of neural stem cells against traumatic axonal injury. J Neurotrauma 29:295-312.

Thonhoff JR, Gao J, Dunn TJ, Ojeda L and Wu P, 2012, Mutant SOD1 Microglia-Generated Nitroxidative Stress Promotes Toxicity to Human Fetal Neural Stem Cell-Derived Motor Neurons through Direct Damage and Noxious Interactions with Astrocytes. Am J Stem Cells 1:2-21.  

Ojeda L, Gao J, Hooten KG, Wang E, Thonhoff JR, Gao T and Wu P, 2011, Critical role of PI3K/Akt/GSK3β in motoneuron specification from human neural stem cells in response to FGF2 and EGF. PLoS ONE 6:e23414.

Jordan PM, Ojeda LD, Thonhoff JR, Gao J, Boehning D, Yu Y and Wu P, 2009, Generation of spinal motor neurons from human fetal brain-derived neural stem cells: role of basic fibroblast growth factor. J Neurosci Res 87(2):318-32.

Thonhoff JR, Lou DI, Jordan PM, Zhao X and Wu P, 2008, Compatibility of human fetal neural stem cells with bioengineering hydrogels in vitro. Brain Res 1187:42-51.

Jordan P, Cain L and Wu P, 2007, Astrocytes Enhance Long-Term Survival of Cholinergic Neurons Differentiated from Human Fetal Neural Stem Cells. J Neurosc Res 86:35-47.

Tarasenko YI, Nie L, McAdoo DJ, Johnson KM, Hulsebosch CE, Grady JJ and Wu P 2007, Human fetal neural stem cells grafted into contusion-injured rat spinal cord improve behavior. J Neurosc Res 85:47-57 (doi:10.1002/jnr.21098).

Gao J, Prough DS, McAdoo DJ, Grady JJ, Parsley MO, Ma L, Tarasenko YI and Wu P, 2006, Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury. Exp Neurol 201:281-92.

Cai Y, Wu P, Ozen M, Yu Y, Wang J, Ittmann M and Liu M, 2006, Gene expression profiling and analysis of signaling pathways involved in priming and differentiation of human neural stem cells. Neurosc 138(1):133-48.

Gao J, Coggeshall R, Tarasenko YI and Wu P, 2005, Human neural stem cell-derived cholinergic neurons innervate muscle in motoneuron deficient adult rats. Neurosc 131:257-262.

Tarasenko YI, Nie L, McAdoo DJ, Johnson KM, Hulsebosch CE, Grady JJ and Wu P 2007, Human fetal neural stem cells grafted into contusion-injured rat spinal cord improve behavior. J Neurosc Res 85:47-57 (doi:10.1002/jnr.21098).

Xu Y, Gu Y, Xu GY, Wu P, Li G-W and Huang L-Y M, 2003, Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons- a novel strategy to increase opioid antinociception. Proc. Nat. Acad. Sci. USA 100:6204-6209.

Wu P, Tarasenko YI, Gu Y, Huang L-Y M, Coggeshall R and Yu Y, 2002, Region-specific generation of cholinergic neurons from human neural stem cells grafted in adult rat. Nat Neurosci 5 (12):1271-1278.

Wu P, Ye Y and Svendsen CN, 2002, Transduction of human neural progenitor cells using recombinant adeno-associated viral vectors. Gene Therapy 9:245-255.

Nguyen JT, Wu P, Clouse ME, Terwilliger EF and Hlatky L, 1998, AAV-mediated delivery of anti-angiogenic factors as an anti-tumor strategy.  Cancer Res 58(24): 5673-5677.

Wu P, Phillips MI, Bui J and Terwilliger EF, 1998, Adeno-associated virus vector-mediated transgene integration into brain and other nondividing targets. J Virol 72:5919-5926.

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=HistorySearch&query_key=3&db=pubmed&hinit=true