Junfang Wu, BM, PhD

Jakovceyski I, Wu J * (co-first author), Karl N, Leshchyns’ka I, Sytnyk V, Chen J, Irintchev A, Schachner M. Glial scar expression of CHL1, the close homolog of the adhesion molecule CHL1 limits recovery after spinal cord injury. Journal of Neuroscience, 2007, 27(27): 7222-7233.    **Highlighted by Nature Medicine

Wu J, Yoo S, Wilcock D, Lytle LM, Leung PY, Colton CA, Wrathall JR. Interaction of NG2⁺ glial progenitors and microglia/macrophages from the injured spinal cord. GLIA, 2010, 58(4):410-422.

Wu J, Renn CL, Faden AI, Dorsey SG. TrkB.T1 contributes to neuropathic pain following spinal cord Injury through regulation of cell cycle pathways. Journal of Neuroscience, 2013, 33(30):12447-12463. PMID: 23884949.

Wu J, Zhao Z, Sabirzhanov B, Stoica BA, Kumar A, Luo T, Skovira J, Fade AI. Spinal cord injury causes brain inflammation associated with cognitive and affective changes: role of cell cycle pathways. Journal of Neuroscience, 2014, 34(33): 10989-11006. PMID: 25122899.

Liu S, Sarkar C, Dinizo M, Faden AI, Koh EY, Lipinski MM, Wu J. Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death. Cell Death & Disease. 2015, 6: PMID: 25569099.

Wu J, Zhao Z, Zhu X, Renn CL, Dorsey SG, Faden AI. Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury. Pain, 2016, 157(2):488-503. PMID: 26797506.

Wu J and Lipinski MM. Autophagy in neurotrauma: good or bad or dysregulated. Cells, 2019 Jul 10; 8(7): 693. doi: 10.3390/cells8070693.pii: PMID: 31295858. Review.

Sabirzhanov B, Matyas J, Coll-Miro M, Yu L, Faden AI, Stoica BA, Wu J. Inhibition of microRNA-711 limits Ang-1 and Akt changes, tissue damage, and neurological dysfunction after contusive spinal cord injury in mice. Cell Death & Disease, 2019, 10(11):839. PMID: 31685802.

Ritzel RM, Li Y, He J, Khan N, Doran S, Faden AI, and Wu J. Sustained neuronal and microglial alterations are associated with diverse neurobehavioral dysfunction long after experimental brain injury. Neurobiology of Disease, 2020; 136:104713. PMID: 31843705

Li Y, Ritzel RM, He J, Cao T, Sabirzhanov B, Li H, Liu S, Wu L-J, Wu J. The voltage-gated proton channel Hv1 plays a detrimental role in contusion spinal cord injury via extracellular acidosis-mediated neuroinflammation. Brain, Behavior, and Immunity, 2021, 91: 267-283. PMID: 33039662.

Zou L, He J, Gu L, Shahror RA, Li Y, Cao T, Zhu J, Wang S, Fan X, Wu J#, Chao W. Brain Innate Immune Response via Extracellular miRNA-TLR7 Sensing during Polymicrobial Sepsis. Brain, Behavior, and Immunity. 2022 Feb, 100: 10-24. PMID: 34808293. (# correspondent)

Lei Z, Ritzel RM, Li Y, Li H, Faden AI, Wu J. Old age alters inflammation and autophagy signaling in the brain, leading to exacerbated neurological outcomes after spinal cord injury in male mice. Brain, Behavior, and Immunity, 2024 Aug; 120: 439-451. PMID: 38925420.

Park C, Lei Z, Li Y, Ren B, He J, Huang H, Chen F, Jones M, Li H, Brunner K, Zhu J, Jay SM, Williams B, Chao W, Wu J#, Zou L#. Extracellular vesicles in sepsis plasma mediate neuronal inflammation in the brain through miRNAs and innate immune signaling. Journal of Neuroinflammation, 2024 Oct 7;21(1):252. doi: 10.1186/s12974-024-03250-0. PMID: 39375720.

Neuroinflammation and Neuroprotection Following CNS Trauma

The focus of research in Dr. Wu’s laboratory is to understand the cellular and molecular mechanisms of neurological dysfunction following spinal cord injury (SCI) and traumatic brain injury (TBI), with the ultimate goal of developing potentially therapeutic strategies. In particular, we are interested in pathological mechanisms including disruption of autophagy and lysosomal pathway, astrocytic TrkB.T1, microglial Hv1 channel, NOX2, extracellular vesicles (EVs), and their contribution to neuroinflammation and neurodegeneration in both acute CNS trauma and aging conditions including chronic SCI/TBI and Alzheimer’s disease and related dementia (AD/ADRD).

Specifically, we focus on:

1. Demonstrating the function and the mechanisms of autophagy-lysosomal pathway in SCI.
2. Elucidating molecular mechanisms responsible for SCI-induced brain neuroinflammation and neurodegeneration.
3. Investigating the role of plasma and tissue extracellular vesicles (EVs) in secondary injury after CNS trauma.
4. Examining the function and mechanism of voltage-gated proton channels Hv1 on neuroinflammation and neuropathic pain after experimental SCI and TBI.
5. Elucidating the inflammatory mechanisms underlying olfactory dysfunction in TBI model and its correlation with late-onset dementia-related pathology. 

Multidisciplinary approaches include rodent models of SCI and TBI, diverse behavioral evaluation, characterization of EVs, quantitative image analysis, as well as molecular and cellular biology.

NIH R01 AG077541
Wu / Liu
06/15/2022- 03/31/2027
Inflammatory Mechanisms Underlying Olfactory Dysfunction in Prognosis of TBI Progression to Dementia
Role: Contact PI

NIH 2RF1 NS094527
Wu / Lipinski
06/01/2016 - 05/31/2027
The Function and Mechanisms of Autophagy in Spinal Cord Injury
Role: Contact PI

NIH R01 NS110825
Junfang Wu
05/15/2020 - 04/30/2025
The Function and Mechanisms of Voltage-Gated Proton Channel Hv1 in Spinal Cord Injury
Role: PI

Chao/ Wu/ Zou
05/01/2019 - 02/29/2025
Targeting Brain Inflammation and Neurological Dysfunction in Sepsis
Role: PD/PI

NIH 1R01NS110635
Faden/ Wu
NCE 04/01/2019 - 03/31/2025 NCE
Mechanism of Inflammatory Related Brain Dysfunction after Spinal Cord Injury
Role: PD/PI

NIH R01NS119275
Kristian
07/01/2021 - 06/30/2026
Using NAD+ Precursor for Treatment of Global Cerebral Ischemia
Role: Co-I

A diverse array of in vivo and in vitro experimental models is used to study pathophysiological mechanisms of SCI and TBI. 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
• FACS analysis, immunohistochemistry and state-of-the-art microscopy (light/fluorescence/confocal)
• image analysis (stereology)
• biochemistry/molecular biology (qPCR, Western, etc)

Laboratory Personnel:

• Yun Li, PhD, Research Associate
• Fengshan Yu, MD, Research Associate
• Zhuofan Lei, PhD, Post-doctoral Fellow
• Balaji Krishnamachary, PhD, Post-doctoral Fellow
• Daniela Lecca, PhD, Post-doctoral Fellow
• Zihui Wang, PhD, Postdoctoral Fellow
• Hui Li, BM, MS, Research Assistant