Veronica I. Shubayev, M.D.

Our research is focused on identifying the mechanisms of neuroinflammation associated with neuronal damage and pain. We aim to characterize the role of extracellular protease-cytokine network in modulating glial activation, macrophage recruitment, demyelination and hyperalgesia associated with neuronal injury.  An important strategy of our research is to utilize the peripheral (i.e. sciatic) nerve injury as a model neuronal regeneration system in identifying the pathways of matrix metalloproteinase (MMP) regulation of neuronal and glial survival and phenotypic remodeling. A dedicated NIH program centers on validating MMPs as early universal biomarkers of neuronal degeneration. A second focus of research is on the mechanisms of localized and central neuroinflammation leading to persistent pain. Through award-winning work, we identified TNF-a as a matrix-bound component of nucleus pulposus of lumbar disc and a therapeutic target for radiculopathy. Our discovery of the ability of TNF-a to undergo axonal transport from peripheral injury to segmental spinal cord provided a unique mechanism of axonal-glial crosstalk, central glial activation and neuroinflammation. Other interests in the laboratory include a collaborative research with the Department of Material Sciences at UCSD aims to assess thera-diagnostic capabilities of magnetic nanoparticles in clinical and basic neurosciences, and to engineer the particles with the appropriate surface chemistry for optimal biodistribution and limited neurotoxicity.

Selected References
Chattopadhyay S, Myers R, Janes J, Shubayev V: Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve. Special Issue on Immune and Glial Regulation of Pain, Brain, Behavior & Immunity, 21 (5): 561-8, 2007

Pisanic T, Blackwell J, Shubayev VI, Finones R, Jin S: Nanotoxicity of iron oxide nanoparticle internalization in growing neurons, Biomaterials, 28 (16): 2572-81, 2007
Shubayev VI, Angert M, Dolkas J, Campana WM, Palenscar K, Myers RR. TNFalpha-induced MMP-9 promotes macrophage recruitment into injured peripheral nerve. Mol Cell Neurosci. 31:407-415, 2006.

Myers RR, Campana WC, Shubayev VI: The role of neuroinflammation in neuropathic pain: mechanisms and therapeutic targets, Drug Discovery Today, 11 (1/2): 8-20, 2006

Shubayev VI and Myers RR: Matrix Metalloproteinase-9 (MMP-9) promotes NGF-induced neurite elongation and branching but not new sprout formation in vitro. J. Neuroscience Research 77 (2): 229-239, 2004

Shubayev VI and Myers RR: Endoneurial remodeling by TNF-a and TNF-a-releasing proteases. A spatial and temporal co-localization study in painful neuropathy. J. Peripheral Nervous System 7: 1-9, 2002

Shubayev VI and Myers RR: Axonal transport of TNF-a in painful neuropathy: Distribution of ligand tracer and TNF receptors. J. Neuroimmunology 114 (1-2): 48-56, 2001

Igarashi T, Kikuchi S, Shubayev V, Myers RR. 2000 Volvo Award Winner in Basic Science Studies: Exogenous TNF-a mimics nucleus pulposus-induced neuropathology - molecular, histologic, and behavioral comparisons in rats. Spine, 25 (23): 2975-80, 2000