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Department of Anesthesiology Department of Anesthesiology
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  4. Shubayev Research Lab
  5. PNS/CNS Repair

PNS/CNS Repair

injured-spinal-chord-after-conditioning-lesion.png

Regeneration

The adult peripheral nervous systems (PNS) and central nervous systems (CNS) have distinct abilities to regenerate after injury. We are interested in the activity of matrix metalloproteinase (MMP) enzyme family, their tissue inhibitors of metalloproteinases (TIMPs) and substrates (e.g. laminin, fibronectin, cytokines, trophic factors and ion channels) in the function of glia and immune cells during the PNS/CNS reparative processes.

Our Research

Our lab has established a number of signaling events of neurovascular permeability and immune cell function, neuro-glial cross-talk, axonal growth and myelination controlled by the MMP/TIMP axis. The overall goal of this program is to develop new strategies to improve regenerative capacity of the damaged PNS and CNS.

Representative Papers

  1. Shubayev VI, Angert M, Dolkas J, Campana WM, Palenscar K, Myers RR: MMP-9 mediates TNF-alpha induced macrophage recruitment into peripheral nerve. Mol. Cell Neurosci., 31 (3): 407-15, 2006.
  2. Chattopadhyay S, Shubayev VI: MMP-9 controls Schwann cell proliferation and phenotypic remodeling via IGF-1 and ErbB receptor-mediated activation of MEK/ERK pathway, Glia, 57 (12): 1316-25, 2009.
  3. Liu H, Kim YS, Chattopadhyay S, Shubayev I, Dolkas J, Shubayev VI: MMP inhibition enhances the rate of nerve regeneration in vivo by promoting de-differentiation and mitosis of supporting Schwann cells, J. Neuropathol. Exp. Neurol., 69 (4): 386-95, 2010.
  4. Liu H, Shubayev VI: Matrix metalloproteinase-9 controls proliferation of NG2+ glial progenitors immediately after spinal cord injury, Exp Neurol, 231 (2): 236-46, 2011Liu H, Angert M, Nishihara T, Shubayev I, Dolkas J, Shubayev VI: Spinal glia division contributes to conditioning lesion-induced axon regeneration into the injured spinal cord: Potential role of cyclic AMP-induced TIMP-1, J. Neuropathol. Exp. Neurol., 74 (6): 500-11, 2015.
  5. Kim Y, Remacle GA, Chernov AV, Liu H, Shubayev I, Lai C, Dolkas J, Shiryaev SA, Golubkov VS, Mizisin AP, Strongin AY, Shubayev VI. The MMP-9/TIMP-1 axis controls the status of differentiation and function of myelin-forming Schwann cells in nerve regeneration, PLoS One, 7(3): e33664, 2012.
  6. He W, Bai G, Zhou H, Wei N, White MN, Lauer J, Liu H, Shi Y, Dumitru CD, Lettieri K, Shubayev V, Jordanova A, Guergueltcheva V, Griffin PL, Burgess RW, Pfaff SL, Yang XL: CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase, Nature, 526 (7575): 710-14, 2015.
  7. Nishihara T, Remacle AG, Angert M, Shubayev I, Dolkas J, Chernov AV, Strongin AY, Shubayev VI: Matrix metalloproteinase-14 both sheds cell surface NG2 proteoglycan on macrophages and governs the response to peripheral nerve injury, J. Biol. Chem., 290 (6): 3693-707, 2015.