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1980- B.S. in Neuroscience, Texas Christian University (mentor: Fred H. Gage)
1984- Ph.D. in Physiological Psychology, State University of New York at Binghamton (mentor: Robert L. Isaacson)
1984-1988 Postdoctoral training at University of Rochester Medical School (mentor: Rebekah Loy)
Mitochondrial Function, microRNA (miRNA) Activity and Cell Death in Traumatic Brain and Spinal Cord Injury-
The goal of our research is to limit cell loss and the resulting neurological deficits following CNS injury by targeting steps occurring early in the cell death process. Recently, we have focused our efforts on identifying the mitochondrial events responsible for regulating cell survival and death. Our current studies have revealed a novel role for mitochondria in the regulation of cellular miRNA activity. In particular, we have observed that traumatic brain injury results in a compartmental shift of miRNAs regulating inflammation and in particular, macrophage phenotype. One such miRNA is miR-146a, which targets TRAF6 and IRAK1 and down-regulates markers of the pro-inflammatory macrophage phenotype while facilitating expression of the anti-inflammatory phenotype. We are currently investigating nanocarrier-based cell delivery strategies to introduce inflammatory-related miRNA mimics/inhibitors to the injured brain as a way of targeting pro-inflammatory signaling and prompting reparative macrophage expression. These novel studies are being conducted by Wangxia Wang, Paresh Prajapati, Steven Pesina, and Urim Gelleta in collaboration with Pat Sullivan, John Gensel, and Vincent Venditto.
Wang-Xia Wang, Ph.D., Research Assistant Professor
Paresh Prajapati, Ph.D., Lab Manager, Postdoctoral Scholar
Steven Pesina, Lab Tech, B.S. Chemistry
Urim Geleta, Neuroscience/Psychology major
- Wang, WX ; Prajapati, P ; Vekaria, HJ ; Spry, M ; Cloud, AL ; Sullivan, PG ; Springer, JE "Temporal changes in inflammatory mitochondria-enriched microRNAs following traumatic brain injury and effects of miR-146a nanoparticle delivery." Neural regeneration research 16, 3 (2021): 514-522. [PubMed Link] | [ Full text ]
- Wang, WX ; Prajapati, P ; Nelson, PT ; Springer, JE "The Mitochondria-Associated ER Membranes Are Novel Subcellular Locations Enriched for Inflammatory-Responsive MicroRNAs." Molecular neurobiology 57, 7 (2020): 2996-3013. [PubMed Link] | [ Full text ]
- Prajapati, P ; Wang, WX ; Nelson, PT ; Springer, JE "Methodology for Subcellular Fractionation and MicroRNA Examination of Mitochondria, Mitochondria Associated ER Membrane (MAM), ER, and Cytosol from Human Brain." Methods in molecular biology (Clifton, N.J.) 2063, (2020): 139-154. [PubMed Link] | [ Full text ]
- Prajapati, P ; Dalwadi, P ; Gohel, D ; Singh, K.; Sripada, L ; Bhatelia, K ; Joshi, B ; Roy, M.; Wang, WX ; Springer, JE ; Singh, R.; Singh, R. "Enforced lysosomal biogenesis rescues erythromycin- and clindamycin-induced mitochondria-mediated cell death in human cells." Molecular and cellular biochemistry 461, 1-2 (2019): 23-36. [PubMed Link] | [ Full text ]
- Hubbard, WB ; Harwood, CL ; Prajapati, P ; Springer, JE ; Saatman, KE ; Sullivan, PG "Fractionated mitochondrial magnetic separation for isolation of synaptic mitochondria from brain tissue." Scientific reports 9, 1 (2019): 9656. [PubMed Link] | [ Full text ]
- Barnett, LB ; Springer, JE ; Worthing, RM "Re: Aerobic Exercise Combined with Noninvasive Positive Pressure Ventilation Increases Serum Brain-Derived Neurotrophic Factor in Healthy Males by Kawazu et al." PM & R : the journal of injury, function, and rehabilitation 10, 9 (2018): 988. [PubMed Link] | [ Full text ]
- Raut, N.; Nagar, VR ; Springer, JE ; Sawaki, L.; Salles, SS "Rehabilitation Outcomes in Spinal Abscess Patients With and Without a History of Intravenous Substance Abuse." American journal of physical medicine & rehabilitation 97, 6 (2018): 397-400. [PubMed Link] | [ Full text ]
- Springer, JE ; Visavadiya, NP ; Sullivan, PG ; Hall, ED "Post-Injury Treatment with NIM811 Promotes Recovery of Function in Adult Female Rats after Spinal Cord Contusion: A Dose-Response Study." Journal of neurotrauma 35, 3 (2018): 492-499. [PubMed Link] | [ Full text ]
- Springer, JE ; Prajapati, P ; Sullivan, PG "Targeting the mitochondrial permeability transition pore in traumatic central nervous system injury." Neural regeneration research 13, 8 (2018): 1338-1341. [PubMed Link] | [ Full text ]
- Wang, WX ; Sullivan, PG ; Springer, JE "Mitochondria and microRNA crosstalk in traumatic brain injury." Progress in neuro-psychopharmacology & biological psychiatry 73, (2017): 104-108. [PubMed Link] | [ Full text ]
- Visavadiya, NP ; Springer, JE "Altered Cerebellar Circuitry following Thoracic Spinal Cord Injury in Adult Rats." Neural plasticity 2016, (2016): 8181393. [PubMed Link] | [ Full text ]
- Nagar, VR ; Springer, JE ; Salles, S. "Increased Incidence of Spinal Abscess and Substance Abuse after Implementation of State Mandated Prescription Drug Legislation." Pain medicine (Malden, Mass.) 16, 10 (2015): 2031-5. [PubMed Link] | [ Full text ]
- Wang, WX ; Visavadiya, NP ; Pandya, JD ; Nelson, PT ; Sullivan, PG ; Springer, JE "Mitochondria-associated microRNAs in rat hippocampus following traumatic brain injury." Experimental neurology 265, (2015): 84-93. [PubMed Link] | [ Full text ]
- Wang, WX ; Springer, JE "Role of mitochondria in regulating microRNA activity and its relevance to the central nervous system." Neural regeneration research 10, 7 (2015): 1026-8. [PubMed Link] | [ Full text ]
- Chen, A.; Sun, S.; Ravikumar, R.; Visavadiya, NP ; Springer, JE "Differential proteomic analysis of acute contusive spinal cord injury in rats using iTRAQ reagent labeling and LC-MS/MS." Neurochemical research 38, 11 (2013): 2247-55. [PubMed Link] | [ Full text ]
- Visavadiya, NP ; McEwen, ML ; Pandya, JD ; Sullivan, PG ; Gwag, BJ ; Springer, JE "Antioxidant properties of Neu2000 on mitochondrial free radicals and oxidative damage." Toxicology in vitro : an international journal published in association with BIBRA 27, 2 (2013): 788-97. [PubMed Link] | [ Full text ]
- Readnower, RD ; Pandya, JD ; McEwen, ML ; Pauly, JR ; Springer, JE ; Sullivan, PG "Post-injury administration of the mitochondrial permeability transition pore inhibitor, NIM811, is neuroprotective and improves cognition after traumatic brain injury in rats." Journal of neurotrauma 28, 9 (2011): 1845-53. [PubMed Link] | [ Full text ]
- Rabchevsky, AG ; Patel, SP ; Springer, JE "Pharmacological interventions for spinal cord injury: where do we stand? How might we step forward?" Pharmacology & therapeutics 132, 1 (2011): 15-29. [PubMed Link] | [ Full text ]
- McEwen, ML ; Sullivan, PG ; Rabchevsky, AG ; Springer, JE "Targeting mitochondrial function for the treatment of acute spinal cord injury." Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 8, 2 (2011): 168-79. [PubMed Link] | [ Full text ]
- Springer, JE ; Rao, RR ; Lim, HR ; Cho, SI ; Moon, GJ ; Lee, HY ; Park, EJ ; Noh, JS ; Gwag, BJ "The functional and neuroprotective actions of Neu2000, a dual-acting pharmacological agent, in the treatment of acute spinal cord injury." Journal of neurotrauma 27, 1 (2010): 139-49. [PubMed Link] | [ Full text ]
- Chen, A.; McEwen, ML ; Sun, S.; Ravikumar, R.; Springer, JE "Proteomic and phosphoproteomic analyses of the soluble fraction following acute spinal cord contusion in rats." Journal of neurotrauma 27, 1 (2010): 263-74. [PubMed Link] | [ Full text ]
- Chen, A.; Springer, JE "Neuroproteomic methods in spinal cord injury." Methods in molecular biology (Clifton, N.J.) 566, (2009): 57-67. [PubMed Link] | [ Full text ]
- Pettigrew, LC ; Kindy, MS ; Scheff, S.; Springer, JE ; Kryscio, RJ ; Li, Y.; Grass, DS "Focal cerebral ischemia in the TNFalpha-transgenic rat." Journal of neuroinflammation 5, (2008): 47. [PubMed Link] | [ Full text ]
- Mbye, LH ; Singh, IN ; Sullivan, PG ; Springer, JE ; Hall, ED "Attenuation of acute mitochondrial dysfunction after traumatic brain injury in mice by NIM811, a non-immunosuppressive cyclosporin A analog." Experimental neurology 209, 1 (2008): 243-53. [PubMed Link] | [ Full text ]
- Ravikumar, R.; McEwen, ML ; Springer, JE "Post-treatment with the cyclosporin derivative, NIM811, reduced indices of cell death and increased the volume of spared tissue in the acute period following spinal cord contusion." Journal of neurotrauma 24, 10 (2007): 1618-30. [PubMed Link] | [ Full text ]
- McEwen, ML ; Sullivan, PG ; Springer, JE "Pretreatment with the cyclosporin derivative, NIM811, improves the function of synaptic mitochondria following spinal cord contusion in rats." Journal of neurotrauma 24, 4 (2007): 613-24. [PubMed Link] | [ Full text ]
- McEwen, ML ; Springer, JE "Quantification of locomotor recovery following spinal cord contusion in adult rats." Journal of neurotrauma 23, 11 (2006): 1632-53. [PubMed Link] | [ Full text ]
- McEwen, ML ; Springer, JE "A mapping study of caspase-3 activation following acute spinal cord contusion in rats." The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 53, 7 (2005): 809-19. [PubMed Link] | [ Full text ]
- Sullivan, PG ; Rabchevsky, AG ; Waldmeier, PC ; Springer, JE "Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death?" Journal of neuroscience research 79, 1-2 (2005): 231-9. [PubMed Link] | [ Full text ]
- Jin, Y.; McEwen, ML ; Nottingham, SA ; Maragos, WF ; Dragicevic, NB ; Sullivan, PG ; Springer, JE "The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord." Journal of neurotrauma 21, 10 (2004): 1396-404. [PubMed Link] | [ Full text ]
- Hall, ED ; Springer, JE "Neuroprotection and acute spinal cord injury: a reappraisal." NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics 1, 1 (2004): 80-100. [PubMed Link] | [ Full text ]
- Jin, Y.; McEwen, ML ; Ghandour, MS ; Springer, JE "Overexpression of XIAP inhibits apoptotic cell death in an oligodendroglial cell line." Cellular and molecular neurobiology 24, 6 (2004): 853-63. [PubMed Link] |
- Sullivan, PG ; Springer, JE ; Hall, ED ; Scheff, SW "Mitochondrial uncoupling as a therapeutic target following neuronal injury." Journal of bioenergetics and biomembranes 36, 4 (2004): 353-6. [PubMed Link] |
- Nottingham, SA ; Springer, JE "Temporal and spatial distribution of activated caspase-3 after subdural kainic acid infusions in rat spinal cord." The Journal of comparative neurology 464, 4 (2003): 463-71. [PubMed Link] | [ Full text ]
- Garrido, R.; Springer, JE ; Hennig, B.; Toborek, M. "Apoptosis of spinal cord neurons by preventing depletion nicotine attenuates arachidonic acid-induced of neurotrophic factors." Journal of neurotrauma 20, 11 (2003): 1201-13. [PubMed Link] | [ Full text ]
- Candelario-Jalil, E.; González-Falcón, A.; García-Cabrera, M.; Alvarez, D.; Al-Dalain, S.; Martinez, G.; León, OS ; Springer, JE "Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia." Journal of neurochemistry 86, 3 (2003): 545-55. [PubMed Link] | [ Full text ]
- Springer, JE "Apoptotic cell death following traumatic injury to the central nervous system." Journal of biochemistry and molecular biology 35, 1 (2002): 94-105. [PubMed Link] |
- Mu, X.; Azbill, RD ; Springer, JE "NBQX treatment improves mitochondrial function and reduces oxidative events after spinal cord injury." Journal of neurotrauma 19, 8 (2002): 917-27. [PubMed Link] | [ Full text ]
- Zwick, M.; Teng, L.; Mu, X.; Springer, JE ; Davis, BM "Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation." Experimental neurology 171, 2 (2001): 342-50. [PubMed Link] | [ Full text ]
- Springer, JE ; Nottingham, SA ; McEwen, ML ; Azbill, RD ; Jin, Y. "Caspase-3 apoptotic signaling following injury to the central nervous system." Clinical chemistry and laboratory medicine 39, 4 (2001): 299-307. [PubMed Link] | [ Full text ]
- Mu, X.; Azbill, RD ; Springer, JE "Riluzole and methylprednisolone combined treatment improves functional recovery in traumatic spinal cord injury." Journal of neurotrauma 17, 9 (2000): 773-80. [PubMed Link] | [ Full text ]
- Springer, JE ; Azbill, RD ; Nottingham, SA ; Kennedy, SE "Calcineurin-mediated BAD dephosphorylation activates the caspase-3 apoptotic cascade in traumatic spinal cord injury." The Journal of neuroscience : the official journal of the Society for Neuroscience 20, 19 (2000): 7246-51. [PubMed Link] | [ Full text ]
- Mu, X.; Azbill, RD ; Springer, JE "Riluzole improves measures of oxidative stress following traumatic spinal cord injury." Brain research 870, 1-2 (2000): 66-72. [PubMed Link] | [ Full text ]
- Azbill, RD ; Mu, X.; Springer, JE "Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes." Brain research 871, 2 (2000): 175-80. [PubMed Link] | [ Full text ]
- Kruman, II ; Pedersen, WA ; Springer, JE ; Mattson, MP "ALS-linked Cu/Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis." Experimental neurology 160, 1 (1999): 28-39. [PubMed Link] | [ Full text ]
- Springer, JE ; Azbill, RD ; Knapp, PE "Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury." Nature medicine 5, 8 (1999): 943-6. [PubMed Link] | [ Full text ]
- Carlson, SL ; Parrish, ME ; Springer, JE ; Doty, K.; Dossett, L. "Acute inflammatory response in spinal cord following impact injury." Experimental neurology 151, 1 (1998): 77-88. [PubMed Link] | [ Full text ]
- Springer, JE ; Azbill, RD ; Carlson, SL "A rapid and sensitive assay for measuring mitochondrial metabolic activity in isolated neural tissue." Brain research. Brain research protocols 2, 4 (1998): 259-63. [PubMed Link] | [ Full text ]
- Glazner, GW ; Mu, X.; Springer, JE "Localization of glial cell line-derived neurotrophic factor receptor alpha and c-ret mRNA in rat central nervous system." The Journal of comparative neurology 391, 1 (1998): 42-9. [PubMed Link] | [ Full text ]
- Springer, JE ; Azbill, RD ; Kennedy, SE ; George, J.; Geddes, JW "Rapid calpain I activation and cytoskeletal protein degradation following traumatic spinal cord injury: attenuation with riluzole pretreatment." Journal of neurochemistry 69, 4 (1997): 1592-600. [PubMed Link] | [ Full text ]
- Springer, JE ; Azbill, RD ; Mark, RJ ; Begley, JG ; Waeg, G.; Mattson, MP "4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake." Journal of neurochemistry 68, 6 (1997): 2469-76. [PubMed Link] | [ Full text ]
- Mu, X.; Springer, JE ; Bowser, R. "FAC1 expression and localization in motor neurons of developing, adult, and amyotrophic lateral sclerosis spinal cord." Experimental neurology 146, 1 (1997): 17-24. [PubMed Link] | [ Full text ]
- Azbill, RD ; Mu, X.; Bruce-Keller, AJ ; Mattson, MP ; Springer, JE "Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury." Brain research 765, 2 (1997): 283-90. [PubMed Link] | [ Full text ]