The main goal of the Shubayev Lab is to understand the interactions between the immune and nervous systems responsible in the CNS/PNS damage, and to develop novel therapeutic strategies to promote regeneration and manage neuropathic pain. The three main areas of investigation include:
- Extracellular proteolysis in CNS/PNS damage: By proteolysis and interaction with extracellular and cell surface proteins, matrix metalloproteinases (MMPs) control cell signaling and function of neurons and regenerative/progenitor glia during immune response to CNS/PNS damage, the neuro-glial crosstalk, myelin turnover, and axonal growth (1-4).
- Inflammation and neuropathic pain (NP): NP (pain caused by damage or disease of the somatosensory nervous system) is refractory to current therapeutics. The Shubayev laboratory helped define the role of immune cells and certain mediators, such as cytokines and MMPs, in NP. Their work contributed to basic science, such as discovery that inflammatory cytokines undergo axonal transport, and to development of therapeutic strategies in clinics, offering the evidence for TNF-a targeting (e.g. by Enbrel) in treating radiculopathy. Recent work by this group identified myelin basic protein (MBP) as a fundamentally novel pain modulator and implicated myelin sheath damage and repair in NP from mechanical stimulation (1).
- Nanomedicine: The development of effective therapeutics targeting CNS/PNS is limited by the ability of drugs to cross neurovascular barriers. With UCSD engineers, the Shubayev lab is developing nontoxic blood-brain barriers-crossing nanocarrier platforms for future use in personalized medicine (5).
Image representing Shubayev research:
Liu H, Shiryaev SA, Chernov AV, Remacle AG, Kim Y, Shubayev I, Baranovskaya S, Golubkov VS, Strongin AY, Shubayev VI: Immunodominant fragments of myelin basic protein initiate T cell-dependent pain, J. Neuroinflammation, 9 (1): 119, 2012.
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.
Liu H, Shubayev VI: Matrix metalloproteinase-9 controls proliferation of NG2+ glial progenitors immediately after spinal cord injury, Experimental Neurology, 231 (2): 236-46, 2011.
Chattopadhyay S and 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
Shubayev VI, Pisanic TR II, Jin S: Magnetic nanoparticles for theragnostics, Advanced Drug Delivery Reviews, 61 (6): 467-77, 200
Dr. Shubayev started her research of fundamental enzymology as predoctoral fellow at UCSF, Department of Biochemistry & Biophysics (Santi Lab) and then focused on MMP proteolysis at UCSF, Department Pharmaceutical Chemistry (Hawkes Lab). As a T32 NIH fellow in Neurobiology of Pain at UCSD, Department of Anesthesiology (Myers Lab), she pioneered the work on MMPs as modulators of pain and peripheral neuroinflammation. She joined our department and San Diego VA Healthcare System as faculty in 2002.
For more information, please visit http://shubayev.ucsd.edu.