Steven M. LeVine, Ph.D.

Professor
Albert Einstein College of Medicine, 1987


Research Focus

Neurobiology - multiple sclerosis and globoid cell leukodystrophy

Research Interests

We perform translational research that is directed at identifying pathogenic mechanisms and novel interventions for multiple sclerosis, which is a neurological disease that can cause sensory, motor and/or cognitive declines. Our studies incorporate a team approach that includes clinical samples, flow cytometry, immunology, and animal models. Additional studies address intervention strategies for globoid cell leukodystrophy and identifying mechanisms of toxin-induced vessel injury.

Selected Publications

Iron deposits in a cerebral model of multiple sclerosis
Iron deposits in a cerebral model of multiple sclerosis

Multiple Sclerosis

LeVine SM (1997) Iron deposits in multiple sclerosis and Alzheimer’s disease brains. Brain Res. 760:298-303.

Forge JK, Pedchenko TV and LeVine SM (1998) Iron deposits in the central nervous system of SJL mice with experimental allergic encephalomyelitis. Life Sci. 63:2271-2284.

LeVine SM and Wetzel DL (1998) Chemical analysis of multiple sclerosis lesions by FT-IR microspectroscopy. Free Rad. Biol. Med. 25:33-41.

Lynch SG, Fonseca T and LeVine SM (2000) A multiple course of desferrioxamine in chronic progressive multiple sclerosis. Cell. Mol. Biol. 46:865-869.

Emerson ME and LeVine SM (2000) Heme oxygenase-1 and NADPH cytochrome P450 reductase expression in experimental allergic encephalomyelitis. An expanded view of the stress response. J. Neurochem. 75:2555-2562.

Emerson MR, Orentas DM, Lynch SG and LeVine SM (2002) Activation of histamine H2 receptors ameliorates experimental allergic encephalomyelitis. NeuroReport 13:1407-1410.

Chakrabarty A, Emerson MR and LeVine SM (2003) Heme oxygenase-1 in SJL mice with experimental allergic encephalomyelitis. Multiple Sclerosis 9:372-381.

LeVine SM and Chakrabarty A (2004) The role of iron in the pathogenesis of experimental allergic encephalomyelitis and multiple sclerosis. Annals NYAS 1012:252-266.

Emerson ME and LeVine SM (2004) Experimental allergic encephalomyelitis is exacerbated in mice deficient for 12/15-lipoxygenase or 5-lipoxygenase. Brain Res. 1021:140-145.

Mitchell KM, Dotson AM, Cool KM, Chakrabarty A, Benedict SH and LeVine SM (2007) Deferiprone, an orally deliverable iron chelator, ameliorates experimental autoimmune encephalomyelitis. Multiple Sclerosis 13:1118-1126.

Williams R, Rohr AM, Wang W-T, Choi I-Y, Lee P, Berman NEJ, Lynch SG and LeVine SM (2011) Iron deposition is independent of cellular inflammation in a cerebral model of multiple sclerosis. BMC Neurosci. 12:59.

Sweeney ME, Slusser JG, Lynch SG, Benedict SH, Garcia SL, Rues L and LeVine SM (2011) Deferiprone modulates in vitro responses by peripheral blood T cells from control and relapsing remitting multiple sclerosis subjects. Int. Immunopharmacol. 11:1796-1801.

Williams R, Buchheit CL, Berman NEJ and LeVine SM (2012) Pathogenic implications of iron accumulation in multiple sclerosis. J. Neurochem. 120:7-25.

Biswas S, Benedict SH, Lynch SG, and LeVine SM (2012) Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis. BMC Med. 10(1):57.

LeVine, SM, Bilgen, M, and Lynch, SG (2013) Iron accumulation in multiple sclerosis: An early pathogenic event. Expert Rev. Neurother. 13:247-250. Key paper evaluation.

Weigel, KJ, Lynch, SG, and LeVine, SM (2014) Iron chelation and multiple sclerosis. ASN Neuro. 6(1):art:e00136

Krabbe Disease (globoid cell leukodystrophy)

LeVine SM and Brown DC (1997) IL-6 and TNFα expression in brains of twitcher, quaking and normal mice. J. Neuroimmunol. 73:47-56.

Orfi L, Larive CK and LeVine SM (1997) Physicochemical characterization of pyschosine by 1H nuclear magnetic resonance and electron microscopy. Lipids 32:1035-1040.

PAS positive globoid cells in a mouse model of Krabbe disease
PAS positive globoid cells in a mouse model of Krabbe disease

Pedchenko TV and LeVine SM (1999) IL-6 deficiency results in enhanced pathology in twitcher (globoid cell leukodystrophy) mice. Exp. Neurol. 158:459-468.

LeVine SM, Pedchenko TV, Bronshteyn IG and Pinson D (2000) L-Cycloserine reduces clinical and pathological signs in mice with globoid cell leukodystrophy (twitcher mice). J. Neurosci. Res. 60:231-236.

Pedchenko TV, Bronshteyn IG and LeVine SM (2000) TNF-receptor 1 deficiency fails to alter the clinical and pathological course in mice with globoid cell leukodystrophy (twitcher mice) but affords protection following LPS challenge. J. Neuroimmunol. 110:186-194.

Biswas S, Bronshteyn IG, Pinson DM and LeVine SM (2001) IL-6 deficiency allows for enhanced therapeutic value after bone marrow transplantation across a minor histocompatibility barrier in twitcher (globoid cell leukodystrophy) mice. J. Neurosci. Res. 65:298-307.

Biswas S and LeVine SM (2002) Substrate reduction therapy enhances the benefits of bone marrow transplantation in young mice with globoid cell leukodystrophy. Pediatric Res. 51:40-47.

Biswas S, Biesiada H, Williams TD and LeVine SM (2002) Delayed clinical and pathological signs in twitcher (globoid cell leukodystrophy) mice on a C57BL/6 x CAST/Ei background. Neurobiol. Dis. 10:344-357.

Biswas S, Biesiada H, Williams TD and LeVine SM (2003) Substrate reduction intervention by L-cycloserine in twitcher mice (globoid cell leukodystrophy) on a B6;CAST/Ei background. Neuroscience Lett. 347:33-36.

Toxin Injury

Culley NC, Pinson DM, Chakrabarty A, Mayo MS and LeVine SM (2005) Pathophysiological manifestations in mice exposed to anthrax lethal toxin. Infect. Immun. 73:7006-7010.

Terra JK, Cote CK, France B, Jenkins AL, Bozue JA, Welkos SL, LeVine SM and Bradley KA (2010) Cutting edge: Resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of Nalp1b/Nlrp1b. J. Immunol. 184:17-20.

Bradley KA and LeVine SM (2010) Athrax toxin delivers a one-two punch. Cell Host Microbe 8:394-395.

Terra JK, France B, Cote CK, Jenkins A, Bozue JA, Welkos SL, Bhargava R, Mehrabian M, Pan C, Lusis AJ, Davis RC, LeVine SM and Bradley KA (2011) Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis. PLoS Pathog. 7(12): e1002469.

Weigel KJ, Rues L, Doyle EJ, Buchheit CL, Wood JG, Gallagher RJ, Kelly LE, Radel JD, Bradley KA, and LeVine SM (2012) Rapid vascular responses to anthrax lethal toxin in mice containing a segment of chromosome 11 from the CAST/Ei strain on a C57BL/6 genetic background. PLoS ONE 7(7): e40126.

Methods and Designs

LeVine SM and Macklin WB (1990) Iron-enriched oligodendrocytes: A reexamination of their spatial distribution. J. Neurosci. Res. 26:508-512.

LeVine SM and Wetzel DL (1994) In situ chemical analyses from frozen tissue sections by Fourier transform infrared microspectroscopy: Examination of white matter exposed to extravasated blood in the rat brain. Amer. J. Path. 145:1041-1047.

LeVine SM, Wulser MJ and Lynch SG (1998) Iron quantification in cerebrospinal fluid. Anal. Biochem. 265:74-78.

Wetzel DL and LeVine SM (1999) Imaging molecular chemistry with infrared microscopy. Science 285:1224-1225.

Duzhak T, Emerson MR, Chakrabarty A, Alterman MA and LeVine SM (2003) Analysis of protein induction in the CNS of SJL mice with experimental allergic encephalomyelitis by proteomic screening and immunohistochemistry. Cell. Mol. Biol. 49:723-732.

Esch SW, Williams TD, Biswas S, Chakrabarty A and LeVine SM (2003) Sphingolipid profile in the CNS of the twitcher (globoid cell leukodystrophy) mouse: A lipidomics approach. Cell. Mol. Biol. 49:779-787.

Chakrabarty A, Fleming KK, Marquis JG and LeVine SM (2005) Quantifying immunohistochemical staining of phospho-eIF2α, heme oxygenase-2 and NADPH cytochrome P450 reductase in oligodendrocytes during experimental autoimmune encephalomyelitis. J. Neurosci. Meth. 144:227-234.

Fleming KK, Bovaird JA, Mosier MC, Emerson MR, LeVine SM and Marquis JG (2005) Statistical analysis of data from studies on experimental autoimmune encephalomyelitis. J. Neuroimmunol. 170:71-84.

Emerson MR, Gallagher RJ, Marquis JG and LeVine SM (2009) Enhancing the ability of experimental autoimmune encephalomyelitis to serve as a more rigorous model of multiple sclerosis through refinement of the experimental design. Comp. Med. 59:112-128.

Last modified: Apr 15, 2014

Contact

Steven M. LeVine, Ph.D.
Professor

2016 Smith East
3901 Rainbow Blvd.
Kansas City, KS 66160

P: (913) 588-7420
F: (913) 588-7430
slevine@kumc.edu

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