Anatomy and Neurobiology
- BM (Clinical Medicine): Jiangxi Medical College, Nanchang, China
- MS (Pharmacology): Jiangxi Medical College, Nanchang, China
- PhD (Neuropharmacology): Nanjing Medical University, Nanjing, China
- Postdoctoral training: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- Postdoctoral training: National Institutes of Health, Bethesda, MD
The overall objective of research in my laboratory is to examine secondary injury processes following traumatic spinal cord injury (SCI) and pharmacological/gene therapeutic interventions for SCI. Specifically, we focus on: (1) Elucidating molecular mechanisms responsible for SCI-induced brain inflammation. This may lead to effective therapeutic interventions that limit post-SCI cognitive decline and depression; (2) Demonstrating the function and the mechanisms of autophagy-lysosomal pathway and specific microRNAs in neuronal injury after SCI which could open a potential novel treatment avenue against SCI as well as identify candidate molecular targets for these manipulations; (3) Identifying the genetic and genomic factors that impact SCI-PAIN as well as identifying new therapeutic targets to reduce or eliminate SCI-PAIN, including a truncated isoform of the BDNF receptor tropomyosin related kinase B (trkB), trkB.T1; (4) Examining the function and mechanism of NOX2 on nocifensive behaviors and central pain regulation after experimental SCI and traumatic brain injury (TBI). My ultimate goal is to understand the cellular and molecular mechanism of functional recovery after SCI and also to develop potentially therapeutic strategies.
Lab Techniques and Equipment:
A diverse array of in vivo and in vitro experimental models is used to study pathophysiological mechanisms of SCI. These include: contusion spinal cord injury (mouse & rat), controlled cortical impact (mouse), behavioral analysis (mechanical/thermal pain, facial spontaneous pain, locomotor/motor, learning and memory, depression/anxiety function), cell cultures (primary microglia, astrocytes, neurons; cell lines), adult microglia/macrophage isolation and FACS analysis, immunohistochemistry and state-of-the-art microscopy (light/fluorescence/confocal) and image analysis (stereology), biochemistry/molecular biology (qPCR, Western, etc).
Active Grant Support:
The Function and Mechanisms of Autophagy in Spinal Cord Injury
NIH/NINDS R01 NS094527 (PI: Junfang Wu)
06/01/16 – 05/31/21
Genetics of Spinal Cord Injury Induced Chronic Pain
NIH P30 NR014129 (Sub-Project PI: Junfang Wu)
07/01/2014 - 06/30/2017
Spinal Mechanisms Underlying SCI-induced Pain: Implications for Targeted Therapy
NIH R01 NR013601 (MPI: Susan G. Dorsey/Alan I. Faden)
03/21/2012 - 02/28/2017
Cell Cycle Pathway Mediates SCI-induced Cognitive Impairment and Depression
Craig H. Nielson Foundation Research, PRTMPL42974 (PI: Alan I. Faden)
09/01/15 - 08/31/18
- Jessica J. Matyas, PhD, Post-doctoral Fellow
- Marina Coll-Miro, PhD, Post-doctoral Fellow
- Yun Li, PhD, Post-doctoral Fellow
- Lijia Yu, BA, Research Assistant
- Wu J, Li J, Huang KP and Huang FL (2002) Attenuation of protein kinase C and cAMP-dependent protein kinase signal transduction in the neurogranin knockout mouse. Journal of Biological Chemistry, 277(22): 19498-19505.
- Wu J, Huang KP and Huang FL (2003) Participation of NMDA-mediated phosphorylation and oxidation of neurogranin in the regulation of Ca2+- and Ca2+/calmodulin-dependent neuronal signaling in the hippocampus. Journal of Neurochemistry, 86: 1524-1533.
- Huang FL, Huang KP, Wu J, Boucheron C (2006) Environmental enrichment enhances neurogranin expression and hippocampal learning and memory but fails to rescue the impairments of neurogranin null mutant mice. Journal of Neuroscience, 26(23): 6230-6237.
- Chen J, Wu J, Irintchev A, Apostolova I, Kuegler S, Skup M, Schachner M (2007) Adeno-associated virus-mediated adhesion molecule L1 expression ameliorates inhibitory glial scar formation and promotes axonal regeneration and functional recovery after spinal cord injury in adult mice. Brain, 130: 954-969.
- Jakovceyski I, Wu J (co-first author), Karl N, Leshchyns’ka I, Sytnyk V, Chen J, Irintchev A, Schachner M (2007) Glial scar expression of CHL1, the close homolog of the adhesion molecule CHL1 limits recovery after spinal cord injury. Journal of Neuroscience, 27(27): 7222-7233.
- Kolata S, Wu J, Light K, Schachner M, Matzel LD (2008) Impaired working memory duration but normal learning abilities found in mice that are conditionally deficient in the close homolog of L1. Journal of Neuroscience, 28(50): 13505-13510.
- Wu J (correspondent), Wrathall JR, Schachner M (2010) Phosphatidylinositol 3-kinase/protein kinase Cd activation induces close homolog of adhesion molecule L1 (CHL1) expression in cultured astrocytes. GLIA, 58(3): 315-328.
- Wu J, Yoo S, Wilcock D, Lytle LM, Leung PY, Colton CA, Wrathall JR (2010) Interaction of NG2+ glial progenitors and microglia/macrophages from the injured spinal cord. GLIA, 58(4):410-422.
- Wu J (correspondent), Leung PY, Sharp A, Lee HJ, Wrathall JR (2011) Increased expression of the close homolog of the adhesion molecule L1 (CHL1) in different cell types over time after rat spinal cord contusion. Journal of Neuroscience Research, 89(5): 628-638.
- Whittaker MT, Zai LJ, Lee HJ, Pajoohesh-Ganji A, Wu J, Sharp A, Wyse R, Wrathall JR (2012). GGF2 (Nrg1- ß3) treatment enhances NG2+ cell response and improves functional recovery after spinal cord injury. GLIA, 60(2): 281-294.
- Dickey JS, Baird BJ, Redon CE, Avdoshina V, Palchik G, Wu J, Kondratyev A, Bonner WM, Martin OA (2012) Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity. Nucleic Acids Res, 40(20):10274-86. PMID: 22941641
- Wu J (correspondent), Stoica BA, Dinizo M, Pajoohesh-Ganji A, Piao C, and Faden AI (2012) Delayed cell cycle pathway modulation facilitates recovery after spinal cord injury. Cell Cycle, 11(9): 1782-1795.
- Wu J (correspondent), Pajoohesh-Ganji A, Stoica BA, Dinizo M, Guanciale K, and Faden AI (2012) Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion. Journal of Neuroinflammation, 9(1): 169-179.
- Wu J (correspondent), Kharebava G, Piao C, Stoica BA, Dinizo M, Sabirzhanov B, Hanscom M, Guanciale K, and Faden AI (2012) Inhibition of E2F1/CDK1 pathway attenuates neuronal apoptosis in vitro and confers neuroprotection after spinal cord injury in vivo. PLoS One, 7(7): e42129.
- Lee HJ, Wu J, Chung J, Wrathall JR (2013). SOX2 expression is up-regulated in adult spinal cord after contusion injury in both glial progenitors and ependymal stem cells. Journal of Neuroscience Research, 91(2):196-210. PMID: 23169458.
- Piao CS, Stoica BA, Wu J, Sabirzhanov B, Zhao Z, Cabatbat R, Loane DJ, Faden AI (2013). Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiology of Disease, 54:252-263. PMID: 23313314
- Wu J (correspondent), Raver C, Piao C, Keller A, Faden AI (2013) Cell cycle activation contributes to increased neuronal activity in the posterior thalamic nucleus and associated chronic hyperalgesia after rat spinal cord contusion. Neurotherapeutics, 10(3):520-538.
- Wu J, Renn CL, Faden AI, Dorsey SG (2013) TrkB.T1 contributes to neuropathic pain following spinal cord Injury through regulation of cell cycle pathways. Journal of Neuroscience, 33(30):12447-12463.
- Luo T, Wu J (co-first author), Kabadi SV, Sabirzhanov B, Guanciale K, Hanscom M, Faden J, Cardiff K, Bengson CJ, Faden AI (2013). Propofol Limits Microglial Activation after Experimental Brain Trauma through Inhibition of Nicotinamide Adenine Dinucleotide Phosphate Oxidase. Anesthesiology, 119(6):1370- 88. PMID: 24121215
- Sabirzhanov B, Zhao Z, Stoica BA, Loane DJ, Wu J, Borroto C, Dorsey SG, Faden AI (2014). Down-regulation of miR-23a and miR-27a following experimental traumatic brain injury induces neuronal cell death through activation of pro-apoptotic Bcl-2 proteins. Journal of Neuroscience, 34(30): 10055-71.
- Wu J (correspondent), Zhao Z, Sabirzhanov B, Stoica BA, Kumar A, Luo T, Skovira J, Fade AI (2014). Spinal cord injury causes brain inflammation associated with cognitive and affective changes: role of cell cycle pathways. Journal of Neuroscience, 34(33): 10989-11006.
- Wu J (correspondent), Stoica BA, Luo T, Sabirzhanov B, Zhao Z, Guanciale K, Nayar SK, Foss CA, Pomper MG, Faden AI (2014). Isolated spinal cord contusion in rats induces chronic brain neuroinflammation, neurodegeneration, and cognitive impairment: Involvement of cell cycle activation. Cell Cycle, 13(15): 2446-2458.
- Liu S, Sarkar C, Dinizo M, Faden AI, Koh EY, Lipinski MM, Wu J (2015). Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death. Cell Death & Disease. 6: e1582
- He X, Lakkarajua SK, Hanscom M, Zhao Z, Wu J, Stoica BA, MacKerell AD, Faden AI, Xue F (2015) Acyl-2-aminobenzimidazoles: a novel class of neuroprotective agents targeting mGluR5. Bioorganic & Medicinal Chemistry, 23(9): 2211-20.
- Lakkaraju SK, Mbatia H, Hanscom M, Zhao Z, Wu J, Stoica BA, MacKerell Jr AD, Faden AI, Xue F (2015) Cyclopropyl-containing positive allosteric modulators targeting metabotropic glutamate receptor subtype 5. Bioorganic & Medicinal Chemistry Letters. 25(11): 2275-9.
- Zhao Z, Sabirzhanov B, Wu J, Faden AI, Stoica BA (2015) Voluntary exercise preconditioning activates multiple anti-apoptotic mechanisms and improves neurological recovery after experimental traumatic brain injury. J Neurotrauma, 32(17):1347-60.
- Wu J (correspondent), Sabirzhanov B, Stoica BA, Lipinski MM, Zhao Z, Zhao S, Ward N, Faden AI (2015) Ablation of the transcription factors E2F1-2 limits neuroinflammation and associated neurological deficits after contusive spinal cord injury. Cell Cycle, 14(23): 3698-712
- Klionsky DJ, et al. (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12(1):1-222.
- Wu J (correspondent), Zhao Z, Zhu X, Renn CL, Dorsey SG, Faden AI (2016) Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury. Pain, 157(2):488-503.
- Sabirzhanov B, Stoica CA, Zhao Z, Loane DJ, Wu J, Dorsey SG, Faden AI (2016). miR-711 up-regulation induces neuronal cell death after traumatic brain injury. Cell Death & Differentiation, 23(4):654-68.
- Skovira JW, Kabadi SV, Wu J, Zhao Z, DuBose J, Rosenthal R, Fiskum G, Faden AI (2016) Simulated aeromedical evacuation exacerbates experimental brain injury. Journal of Neurotrauma, 2016 Jan 7. [Epub ahead of print]
- Wu J (correspondent), Zhao Z, Kumar A, Lipinski MM, Loane DJ, Stoica BA, Faden AI (2016) ER stress and disrupted neurogenesis in the brain are associated with cognitive impairment and depressive-like behavior after spinal cord injury. Journal of Neurotrauma, 2016 Apr 5. [Epub ahead of print] PMID: 27050417
Selected review articles and book chapters:
<Modern Neuroscience Methods>. Wu JF and Liu M. Editor in chief. The Publisher of Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R.China. (1100 pages with A4 paper)
- Wu J, Stoica B, Faden AI (2011) Cell cycle activation and spinal cord injury. Neurotherapeutics, 8(2):221- 228.
- Zhao Z, Wu J (2012). Emotional and anxiety assessments in CNS disorders In: Animal models of acute neurological injuries II: Injury and Mechanistic Assessments. (Chen J, Xu XM, Xu Z, Zhang J. eds). Springer. p255-263.
- Lipinski MM, Wu J, Faden AI, Sarkar C (2015) Function and mechanisms of autophagy in brain and spinal cord trauma. Antioxidants & Redox Signaling, 23(6):565-77.
- Lipinski MM, Wu J (2015) Modification of autophagy-lysosomal pathway as a treatment after spinal cord injury. Neural Regeneration Research, 10(6):892-3. (perspective)
- Faden AI, Wu J, Stoica BA, Loane DJ (2016) Progressive inflammatory-mediated neurodegeneration after traumatic brain or spinal cord injury. British Journal of Pharmacology. 2016 Feb; 173(4): 681-91.