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 (Lous 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).
Recently, through collaboration with investigators in the Center for Addiction Research, we began to study the effects and mechanisms of chronic alcohol consumption on endogenous neural stem cells in rodents. We have also started a collaboration with virologists at UTMB through NeurolD Initiative by applying human neural stem cell-derived neurons and glia for mechanistic studies of viral encephalitis.
Wu P, Zhao Y, Haidacher SJ, Wang E, Parsley MO, Gao J, Sadygov RG, Starkey JM, Luxon BA, Spratt H, DeWitt DS, Prough DS, and Denner L. 2013 Detection of Structural and Metabolic Changes in Traumatically Injured Hippocampus by Quantitative Differential Proteomics. J Neurotrauma 30:775-88
Herin DV, Bubar MJ, Seitz PK, Thomas ML, Hillman GR, Tarasenko YI, Wu P and Cunningham KA, 2013 Elevated expression of Serotonin 5-HT(2A) receptors in the rat ventral tegmental area enhances vulnerability to the behavioral effects of cocaine. Front Psychiatry 4:2.
Li B, Shi Y, Shu J, Gao J, Wu P and Tang S-J, 2013 Wingless-type mammary tumor virus integration site family, member 5A (Wnt5a) regulates human immunodeficiency virus type1 (HIV-1) envelope glycoprotein 120 (gp 120)-induced expression of pro-inflammatory cytokines via the Ca2+/calmodulin-dependent protein kinase II (caMKII) and c-JUN N-terminal kinase (JNK) signaling pathways. J Biol Chem 288:13610-9
Saxena V, Xie G, Li B, Welte T, Gong B, Boor P, Wu P, Tang S-J, Tesh R and Wang T, 2013 A Hamster-Derived West Nile Virus Isolate Induces Persistent Renal Infection in Mice. PLoS Negl Trop Dis 7:e2275.
Gao J, Thonhoff JR, Dunn TJ and Wu P, 2013 Transplantation poses inherent risk to human fetal neural stem cell survival. J Neurorestoerology 1:1-12.
Natarajan R, Singhal V, Benes R, Gao J, Chan H, Chen, H, Zhou J and Wu P, 2014 STAT3 modulation to enhance motor neuron differentiation in human neural stem cells. PLoS One, 9(6):e100405.
Liu Z, Liu Y, Gao R, Li H, Dunn T, Wu P, Smith GR, Sarkar PS and Fang X, 2014 Ethanol Suppresses PGC-1α Expression by Interfering with the cAMP-CREB Pathway in Neuronal Cells. PLoS One, 9(8):e104247.