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William Cafferty, PhD

Associate Professor of Neurology and of Neuroscience

Contact Information

William Cafferty, PhD

Mailing Addresses

  • 300 George Street

    New Haven, CT 06511

    United States

  • Yale University Neurology Department

    PO BOX 208018

    New Haven, CT 06520

    United States

Cafferty Lab

Research Summary

The inability of CNS axons to regenerate and reinnnervate appropriate targets after trauma results in chronic compromise of function that presents a devastating prognosis for TBI, MS, stroke and SCI patients. Numerous studies have identified two broad classes of axon growth inhibitor (AGI) proteins responsible for axon growth arrest, the myelin associated inhibitors (Nogo, MAG, OMgp) and the Chondroitin Sulfate Proteoglycans (CSPGs). Experimental paradigms that negate the activity of these inhibitors in vivo have shown a slight increase in regeneration of damaged axons, but a more dramatic restitution of function. An alternative hypothesis to long-distance axon regeneration-mediated restitution of function would be the reorganization of intact spinal circuitry that often remains after SCI. One of the central goals of my laboratory is to comprehensively evaluate the potential for intact spinal circuits to replace lost connections after SCI, and furthermore define whether negating the action of AGIs supports adaptive or maladaptive axonal reorganization. Complex wiring of the myriad phenotypes of ascending, descending and intrinsic spinal tracts points to tract-specific sensitivity to AGI’s. Understanding the molecular mechanisms that underlie the ability of intact axons to initiate a growth response to adjacent trauma is crucial to the design of therapeutic agents that can either enhance or arrest this response depending on need. Exploiting the plastic potential of intact spinal circuits will offer additional therapeutic tools to encourage restitution of function after CNS injury. In summary, my laboratory is currently utilizing anatomical, electrophysiological, genetic and in vivo imaging methodology to define the extent of plasticity within intact spinal circuitry to investigate the capacity of de novo circuits to restore function after spinal cord injury and therefore reduce the burden of this neurological disease borne by every age group, by every segment of society, by people all over the world.

Coauthors

Research Interests

Brain Diseases; Demyelinating Diseases; Pain; Spinal Cord Injuries; Neurodegenerative Diseases

Selected Publications

  • Reorganization of Intact Descending Motor Circuits to Replace Lost Connections After Injury.Fink KL, Cafferty WB. Reorganization of Intact Descending Motor Circuits to Replace Lost Connections After Injury. Neurotherapeutics : The Journal Of The American Society For Experimental NeuroTherapeutics 2016, 13: 370-81. PMID: 26846379, PMCID: PMC4824020, DOI: 10.1007/s13311-016-0422-x.
  • Leukemia inhibitory factor determines the growth status of injured adult sensory neurons.Cafferty WB, Gardiner NJ, Gavazzi I, Powell J, McMahon SB, Heath JK, Munson J, Cohen J, Thompson SW. Leukemia inhibitory factor determines the growth status of injured adult sensory neurons. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2001, 21: 7161-70. PMID: 11549727.
  • Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1-/- Mice.Fink KL, Strittmatter SM, Cafferty WB. Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1-/- Mice. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2015, 35: 15403-18. PMID: 26586827, PMCID: PMC4649010, DOI: 10.1523/JNEUROSCI.3165-15.2015.
  • Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury.Zou Y, Stagi M, Wang X, Yigitkanli K, Siegel CS, Nakatsu F, Cafferty WB, Strittmatter SM. Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2015, 35: 10429-39. PMID: 26203138, PMCID: PMC4510284, DOI: 10.1523/JNEUROSCI.1718-15.2015.
  • Plasticity of intact rubral projections mediates spontaneous recovery of function after corticospinal tract injury.Siegel CS, Fink KL, Strittmatter SM, Cafferty WB. Plasticity of intact rubral projections mediates spontaneous recovery of function after corticospinal tract injury. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2015, 35: 1443-57. PMID: 25632122, PMCID: PMC4308593, DOI: 10.1523/JNEUROSCI.3713-14.2015.
  • Human NgR-Fc decoy protein via lumbar intrathecal bolus administration enhances recovery from rat spinal cord contusion.Wang X, Yigitkanli K, Kim CY, Sekine-Komo T, Wirak D, Frieden E, Bhargava A, Maynard G, Cafferty WB, Strittmatter SM. Human NgR-Fc decoy protein via lumbar intrathecal bolus administration enhances recovery from rat spinal cord contusion. Journal Of Neurotrauma 2014, 31: 1955-66. PMID: 24964223, PMCID: PMC4245872, DOI: 10.1089/neu.2014.3355.
  • Diffusion tensor imaging as a predictor of locomotor function after experimental spinal cord injury and recovery.Kelley BJ, Harel NY, Kim CY, Papademetris X, Coman D, Wang X, Hasan O, Kaufman A, Globinsky R, Staib LH, Cafferty WB, Hyder F, Strittmatter SM. Diffusion tensor imaging as a predictor of locomotor function after experimental spinal cord injury and recovery. Journal Of Neurotrauma 2014, 31: 1362-73. PMID: 24779685, PMCID: PMC4120934, DOI: 10.1089/neu.2013.3238.
  • Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion.Harel NY, Yigitkanli K, Fu Y, Cafferty WB, Strittmatter SM. Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion. Brain Research 2013, 1538: 17-25. PMID: 24055330, PMCID: PMC3873870, DOI: 10.1016/j.brainres.2013.07.012.
  • Anatomical plasticity of adult brain is titrated by Nogo Receptor 1.Akbik FV, Bhagat SM, Patel PR, Cafferty WB, Strittmatter SM. Anatomical plasticity of adult brain is titrated by Nogo Receptor 1. Neuron 2013, 77: 859-66. PMID: 23473316, PMCID: PMC3594793, DOI: 10.1016/j.neuron.2012.12.027.
  • Axonal regeneration induced by blockade of glial inhibitors coupled with activation of intrinsic neuronal growth pathways.Wang X, Hasan O, Arzeno A, Benowitz LI, Cafferty WB, Strittmatter SM. Axonal regeneration induced by blockade of glial inhibitors coupled with activation of intrinsic neuronal growth pathways. Experimental Neurology 2012, 237: 55-69. PMID: 22728374, PMCID: PMC3418451, DOI: 10.1016/j.expneurol.2012.06.009.
  • PlexinA2 limits recovery from corticospinal axotomy by mediating oligodendrocyte-derived Sema6A growth inhibition.Shim SO, Cafferty WB, Schmidt EC, Kim BG, Fujisawa H, Strittmatter SM. PlexinA2 limits recovery from corticospinal axotomy by mediating oligodendrocyte-derived Sema6A growth inhibition. Molecular And Cellular Neurosciences 2012, 50: 193-200. PMID: 22564823, PMCID: PMC3383336, DOI: 10.1016/j.mcn.2012.04.007.
  • Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury.Duffy P, Wang X, Siegel CS, Tu N, Henkemeyer M, Cafferty WB, Strittmatter SM. Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5063-8. PMID: 22411787, PMCID: PMC3323955, DOI: 10.1073/pnas.1113953109.
  • Myelin associated inhibitors: a link between injury-induced and experience-dependent plasticity.Akbik F, Cafferty WB, Strittmatter SM. Myelin associated inhibitors: a link between injury-induced and experience-dependent plasticity. Experimental Neurology 2012, 235: 43-52. PMID: 21699896, PMCID: PMC3189418, DOI: 10.1016/j.expneurol.2011.06.006.
  • Recovery from chronic spinal cord contusion after Nogo receptor intervention.Wang X, Duffy P, McGee AW, Hasan O, Gould G, Tu N, Harel NY, Huang Y, Carson RE, Weinzimmer D, Ropchan J, Benowitz LI, Cafferty WB, Strittmatter SM. Recovery from chronic spinal cord contusion after Nogo receptor intervention. Annals Of Neurology 2011, 70: 805-21. PMID: 22162062, PMCID: PMC3238798, DOI: 10.1002/ana.22527.
  • MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma.Cafferty WB, Duffy P, Huebner E, Strittmatter SM. MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2010, 30: 6825-37. PMID: 20484625, PMCID: PMC2883258, DOI: 10.1523/JNEUROSCI.6239-09.2010.
  • Rho-associated kinase II (ROCKII) limits axonal growth after trauma within the adult mouse spinal cord.Duffy P, Schmandke A, Schmandke A, Sigworth J, Narumiya S, Cafferty WB, Strittmatter SM. Rho-associated kinase II (ROCKII) limits axonal growth after trauma within the adult mouse spinal cord. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2009, 29: 15266-76. PMID: 19955379, PMCID: PMC2855556, DOI: 10.1523/JNEUROSCI.4650-09.2009.
  • Chondroitinase ABC-mediated plasticity of spinal sensory function.Cafferty WB, Bradbury EJ, Lidierth M, Jones M, Duffy PJ, Pezet S, McMahon SB. Chondroitinase ABC-mediated plasticity of spinal sensory function. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2008, 28: 11998-2009. PMID: 19005065, PMCID: PMC3844838, DOI: 10.1523/JNEUROSCI.3877-08.2008.
  • Reg-2 expression in dorsal root ganglion neurons after adjuvant-induced monoarthritis.Averill S, Inglis JJ, King VR, Thompson SW, Cafferty WB, Shortland PJ, Hunt SP, Kidd BL, Priestley JV. Reg-2 expression in dorsal root ganglion neurons after adjuvant-induced monoarthritis. Neuroscience 2008, 155: 1227-36. PMID: 18652880, DOI: 10.1016/j.neuroscience.2008.06.049.
  • Axonal growth therapeutics: regeneration or sprouting or plasticity?Cafferty WB, McGee AW, Strittmatter SM. Axonal growth therapeutics: regeneration or sprouting or plasticity? Trends In Neurosciences 2008, 31: 215-20. PMID: 18395807, PMCID: PMC2678051, DOI: 10.1016/j.tins.2008.02.004.
  • Response to correspondence: Kim et al., "axon regeneration in young adult mice lacking Nogo-A/B." Neuron 38, 187-199.Cafferty WB, Kim JE, Lee JK, Strittmatter SM. Response to correspondence: Kim et al., "axon regeneration in young adult mice lacking Nogo-A/B." Neuron 38, 187-199. Neuron 2007, 54: 195-9. PMID: 17442242, PMCID: PMC2848952, DOI: 10.1016/j.neuron.2007.04.005.
  • Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans.Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM. Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2007, 27: 2176-85. PMID: 17329414, PMCID: PMC2848955, DOI: 10.1523/JNEUROSCI.5176-06.2007.
  • The Nogo-Nogo receptor pathway limits a spectrum of adult CNS axonal growth.Cafferty WB, Strittmatter SM. The Nogo-Nogo receptor pathway limits a spectrum of adult CNS axonal growth. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2006, 26: 12242-50. PMID: 17122049, PMCID: PMC2848954, DOI: 10.1523/JNEUROSCI.3827-06.2006.
  • Regulation of neuropilin 1 by spinal cord injury in adult rats.Agudo M, Robinson M, Cafferty W, Bradbury EJ, Kilkenny C, Hunt SP, McMahon SB. Regulation of neuropilin 1 by spinal cord injury in adult rats. Molecular And Cellular Neurosciences 2005, 28: 475-84. PMID: 15737738, DOI: 10.1016/j.mcn.2004.10.008.
  • Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation.Qiu J, Cafferty WB, McMahon SB, Thompson SW. Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2005, 25: 1645-53. PMID: 15716400, PMCID: PMC6725934, DOI: 10.1523/JNEUROSCI.3269-04.2005.
  • Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knock-out mice.Cafferty WB, Gardiner NJ, Das P, Qiu J, McMahon SB, Thompson SW. Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knock-out mice. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2004, 24: 4432-43. PMID: 15128857, PMCID: PMC6729445, DOI: 10.1523/JNEUROSCI.2245-02.2004.
  • Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury.Gardiner NJ, Cafferty WB, Slack SE, Thompson SW. Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury. Journal Of Neurochemistry 2002, 83: 100-9. PMID: 12358733, DOI: 10.1046/j.1471-4159.2002.01101.x.
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