Current Projects

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Traumatic axonopathies after diffuse TBI: the role of the SARM1 (Wallerian degeneration) pathway and DLK/LZK mixed lineage cascades
  • NMNAT2-SARM1 signaling in traumatic axonopathy in the corticospinal and visual pathway; NMNAT2-SARM1 neurochemistry; genetic and pharmacological interventions for prevention and treatment of pathology and symptoms

    Blocking of the axon self-destruction enzyme SARM1 with FK866 prevents degeneration of corticospinal axons after acceleration TBI

  • DLK-JNK signaling cascade as mediator of acute and chronic effects of traumatic axonal injury in perikarya and axons of the visual and corticospinal pathway; genetic and pharmacological interventions

    Wallerian degeneration in the optic nerve after acceleration TBI

  • Induction of the dual lineage kinase DLK (top) and downstream phosphorylation of c-JUN (bottom) in injured optic nerve and retina

Restoration of functional connections in the injured brain using optogenetically engineered stem cells
  • Transduction of human NP with hChR2-eYFP-harboring lentivirus and differentiation to optically responsive mature neurons

    Graft of ChR2 (+) human neural progenitors (green, top) turn on host neurons (red nuclei, bottom) when excited by blue light

  • Transplantation of hChR2-eYFP-harboring human neural precursors in mammalian cortex and characterization of structural and functional integration into forebrain circuits

    Functional synapses of human NP-derived neurons: Light-induced post synaptic currents in ChR2 (-) neurons, apparently from stimulation of ChR2 (+) afferents

Structural-functional biomarkers of concussion in the auditory system
  • Exploration of Frequency Following Response as a specific neurophysiological/audiological marker of concussion; predictive modeling using machine learning classifiers; correlations with neuropathology and clinical outcomes

    Differences in auditory brain response between normal (light blue) and TBI subjects (purple) based on frequency domain transform (with Amanda Lauer and Clara Scholl)

Behind-Helmet Blunt (Ballistic) TBI: from neuropathology to protection
  • Neuropathological characterization of behind-helmet blunt TBI in pigs, with emphasis on meningeal and parenchymal macro- and micro-hemorrhages and diffuse axonal injury; correlations among impact severity, meningeal and parenchymal pathology and clinical outcomes

    Diffuse axonal injury in the medullary tegmentum in a pig that became critical after ballistic trauma to the head (APP)

Engineering impact-acceleration models to study concussion in rodents
  • Generation of second-generation models of concussion (founded on the classical Marmarou paradigm) that allow concomitant dialing of impact and acceleration and related measurements with minimal experimenter involvement
Human neuropathology of contusional and diffuse axonal injury
  • Neuropathology of the cortical frontal and subcortical connectome in contusions and diffuse axonal injury: retrograde and transsynaptic neuronal changes signifying injury and degeneration

    Thalamic degeneration (SMI310 staining) after contusions in orbitofrontal and temporopolar cortex indicated on the right