Core Research

POPULATION AND CLUSTER MAPPING

Clusters refer to an unusually high concentration of an illness amongst people within a discrete geography and/or for a discrete period of time.  We reason that Multiple Sclerosis (MS) clusters provide one of the major clues to understanding the cause of MS.

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MYELIN REGENERATION

Early in MS, demyelination is followed by partial or complete remyelination of lesions.  Later in the course of the disease, demyelination occurs without significant remyelination.  Failure of remyelination destabilizes axons and results in secondary and irreversible neurodegeneration.

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THE NEWLY FORMING MULTIPLE SCLEROSIS LESION

In searching for the cause of Multiple Sclerosis, we believe a critical clue comes from the microscopic description of MS lesions at their earliest stage of formation.  Analagous to a crime scene, consider how vital it is to examine evidence as close as possible to the time of the crime.

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Published Research

T2 prep three-dimensional spiral imaging with efficient whole brain coverage for myelin water quantification at 1.5 tesla.
Nguyen TD, Wisnieff C, Cooper MA, Kumar D, Raj A, Spincemaille P, Wang Y, Vartanian T, Gauthier SA.
Magn Reson Med. 2012 Mar;67(3):614-21. doi: 10.1002/mrm.24128. Epub 2012 Jan 3.

Measuring longitudinal myelin water fraction in new multiple sclerosis lesions.
Vargas WS, Monohan E, Pandya S, Raj A, Vartanian T, Nguyen TD, Hurtado Rúa SM, Gauthier SA.
Neuroimage Clin. 2015 Sep 12;9:369-75. doi: 10.1016/j.nicl.2015.09.003. eCollection 2015.

High-resolution anatomic, diffusion tensor, and magnetization transfer magnetic resonance imaging of the optic chiasm at 3T.
Vinogradov E, Degenhardt A, Smith D, Marquis R, Vartanian TK, Kinkel P, Maier SE, Hackney DB, Lenkinski RE.
J Magn Reson Imaging. 2005 Aug;22(2):302-6.

Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease.
Rumah KR, Linden J, Fischetti VA, Vartanian T.
PLoS One. 2013 Oct 16;8(10):e76359. doi: 10.1371/journal.pone.0076359. eCollection 2013.

Neuregulin induces the rapid association of focal adhesion kinase with the erbB2-erbB3 receptor complex in schwann cells.
Vartanian T, Goodearl A, Lefebvre S, Park SK, Fischbach G.
Biochem Biophys Res Commun. 2000 May 10;271(2):414-7.

WAVE1 and regulation of actin nucleation in myelination.
Sloane JA, Vartanian TK.
Neuroscientist. 2007 Oct;13(5):486-91. Review.

The ErbB4 neuregulin receptor mediates suppression of oligodendrocyte maturation.
Sussman CR, Vartanian T, Miller RH.
J Neurosci. 2005 Jun 15;25(24):5757-62.

The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes.
Park SK, Miller R, Krane I, Vartanian T.
J Cell Biol. 2001 Sep 17;154(6):1245-58.

Sonic hedgehog is required during an early phase of oligodendrocyte development in mammalian brain.
Alberta JA, Park SK, Mora J, Yuk D, Pawlitzky I, Iannarelli P, Vartanian T, Stiles CD, Rowitch DH.
Mol Cell Neurosci. 2001 Oct;18(4):434-41.

Axonal neuregulin signals cells of the oligodendrocyte lineage through activation of HER4 and Schwann cells through HER2 and HER3.
Vartanian T, Goodearl A, Viehöver A, Fischbach G.
J Cell Biol. 1997 Apr 7;137(1):211-20.

A role for the acetylcholine receptor-inducing protein ARIA in oligodendrocyte development.
Vartanian T, Corfas G, Li Y, Fischbach GD, Stefansson K.
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11626-30.

Interferon-gamma-induced oligodendrocyte cell death: implications for the pathogenesis of multiple sclerosis.
Vartanian T, Li Y, Zhao M, Stefansson K.
Mol Med. 1995 Nov;1(7):732-43.

Re-evaluating the treatment of acute optic neuritis.
Bennett JL, Nickerson M, Costello F, Sergott RC, Calkwood JC, Galetta SL, Balcer LJ, Markowitz CE, Vartanian T, Morrow M, Moster ML, Taylor AW, Pace TW, Frohman T, Frohman EM.
J Neurol Neurosurg Psychiatry. 2015 Jul;86(7):799-808. doi: 10.1136/jnnp-2014-308185. Epub 2014 Oct 29. Review.

Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes.
Li J, Baud O, Vartanian T, Volpe JJ, Rosenberg PA.
Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9936-41. Epub 2005 Jul 5.

Clostridium perfringens Epsilon Toxin Causes Selective Death of Mature Oligodendrocytes and Central Nervous System Demyelination.
Linden JR, Ma Y, Zhao B, Harris JM, Rumah KR, Schaeren-Wiemers N, Vartanian T.
MBio. 2015 Jun 16;6(3):e02513. doi: 10.1128/mBio.02513-14.

The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ε-Toxin.
Rumah KR, Ma Y, Linden JR, Oo ML, Anrather J, Schaeren-Wiemers N, Alonso MA, Fischetti VA, McClain MS, Vartanian T.
PLoS Pathog. 2015 May 20;11(5):e1004896. doi: 10.1371/journal.ppat.1004896. eCollection 2015 May.

Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals.
Cameron JS, Alexopoulou L, Sloane JA, DiBernardo AB, Ma Y, Kosaras B, Flavell R, Strittmatter SM, Volpe J, Sidman R, Vartanian T.
J Neurosci. 2007 Nov 21;27(47):13033-41.

Purkinje neuron degeneration in nervous (nr) mutant mice is mediated by a metabolic pathway involving excess tissue plasminogen activator.
Li J, Ma Y, Teng YD, Zheng K, Vartanian TK, Snyder EY, Sidman RL.
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7847-52. Epub 2006 May 8.

Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis.
Ma Y, Li J, Chiu I, Wang Y, Sloane JA, Lü J, Kosaras B, Sidman RL, Volpe JJ, Vartanian T.
J Cell Biol. 2006 Oct 23;175(2):209-15.

Nna1 mediates Purkinje cell dendritic development via lysyl oxidase propeptide and NF-κB signaling.
Li J, Gu X, Ma Y, Calicchio ML, Kong D, Teng YD, Yu L, Crain AM, Vartanian TK, Pasqualini R, Arap W, Libermann TA, Snyder EY, Sidman RL.
Neuron. 2010 Oct 6;68(1):45-60. doi: 10.1016/j.neuron.2010.08.013.

TLR8: an innate immune receptor in brain, neurons and axons.
Ma Y, Haynes RL, Sidman RL, Vartanian T.
Cell Cycle. 2007 Dec 1;6(23):2859-68. Epub 2007 Sep 4. Review.

Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination.
Chun SJ, Rasband MN, Sidman RL, Habib AA, Vartanian T.
J Cell Biol. 2003 Oct 27;163(2):397-408. Erratum in: J Cell Biol. 2006 Jul 17;174(2):315.

Increased expression of epidermal growth factor receptor induces sequestration of extracellular signal-related kinases and selective attenuation of specific epidermal growth factor-mediated signal transduction pathways.
Habib AA, Chun SJ, Neel BG, Vartanian T.
Mol Cancer Res. 2003 Jan;1(3):219-33

Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2.
Sloane JA, Batt C, Ma Y, Harris ZM, Trapp B, Vartanian T.
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11555-60. doi: 10.1073/pnas.1006496107. Epub 2010 Jun 3.
GAP-43 as a plasticity protein in neuronal form and repair.
Strittmatter SM, Vartanian T, Fishman MC.
J Neurobiol. 1992 Jul;23(5):507-20. Review.

Carbon monoxide suppresses membrane expression of TLR4 via myeloid differentiation factor-2 in betaTC3 cells.
Rocuts F, Ma Y, Zhang X, Gao W, Yue Y, Vartanian T, Wang H.
J Immunol. 2010 Aug 15;185(4):2134-9. doi: 10.4049/jimmunol.0902782. Epub 2010 Jul 14.

Is multiple sclerosis an autoimmune disease?
Gulcher JR, Vartanian T, Stefansson K.
Clin Neurosci. 1994;2(3-4):246-52. Review.

Impact of neutralizing antibodies on the clinical efficacy of interferon beta in multiple sclerosis.
Vartanian T, Sölberg Sørensen P, Rice G.
J Neurol. 2004 Jun;251 Suppl 2:II25-30.

Neuregulin-induced association of Sos Ras exchange protein with HER2(erbB2)/HER3(erbB3) receptor complexes in Schwann cells through a specific Grb2-HER2(erbB2) interaction.
Goodearl A, Viehover A, Vartanian T.
Dev Neurosci. 2001;23(1):25-30.

Neutralizing antibodies to disease-modifying agents in the treatment of multiple sclerosis.
Vartanian TK, Zamvil SS, Fox E, Sorensen PS.
Neurology. 2004 Dec 14;63(11 Suppl 5):S42-9. Review.

The immunogenicity of disease-modifying therapies for multiple sclerosis: clinical implications for neurologists.
Fox EJ, Vartanian TK, Zamvil SS.
Neurologist. 2007 Nov;13(6):355-62. Review.

The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B. Identification of a novel receptor-tyrosine kinase signalosome.
Habib AA, Chatterjee S, Park SK, Ratan RR, Lefebvre S, Vartanian T.
J Biol Chem. 2001 Mar 23;276(12):8865-74. Epub 2000 Dec 14.

Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway.
Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T.
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8514-9. Epub 2003 Jun 24.

T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS.
Chiu IM, Chen A, Zheng Y, Kosaras B, Tsiftsoglou SA, Vartanian TK, Brown RH Jr, Carroll MC.
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17913-8. doi: 10.1073/pnas.0804610105. Epub 2008 Nov 7.

An examination of the results of the EVIDENCE, INCOMIN, and phase III studies of interferon beta products in the treatment of multiple sclerosis.
Vartanian T.
Clin Ther. 2003 Jan;25(1):105-18. Review.

Clinical and neuropathologic findings in a woman with the FMR1 premutation and multiple sclerosis.
Greco CM, Tassone F, Garcia-Arocena D, Tartaglia N, Coffey SM, Vartanian TK, Brunberg JA, Hagerman PJ, Hagerman RJ.
Arch Neurol. 2008 Aug;65(8):1114-6. doi: 10.1001/archneur.65.8.1114.

Neuregulin: an oligodendrocyte growth factor absent in active multiple sclerosis lesions.
Viehover A, Miller RH, Park SK, Fischbach G, Vartanian T.
Dev Neurosci. 2001;23(4-5):377-86.

Oligodendrocyte substratum adhesion modulates expression of adenylate cyclase-linked receptors.
Vartanian T, Sprinkle TJ, Dawson G, Szuchet S.
Proc Natl Acad Sci U S A. 1988 Feb;85(3):939-43.

Intracellular messengers. Influence of oligodendrocyte substratum adhesion.
Vartanian T, Dawson G, Szuchet S.
Ann N Y Acad Sci. 1988;540:433-6. No abstract available.

Oligodendrocyte-substratum adhesion activates the synthesis of specific lipid species involved in cell signaling.
Vartanian T, Szuchet S, Dawson G.
J Neurosci Res. 1992 May;32(1):69-78.

Phosphorylation of myelin basic protein in intact oligodendrocytes: inhibition by galactosylsphingosine and cyclic AMP.
Vartanian T, Dawson G, Soliven B, Nelson DJ, Szuchet S.
Glia. 1989;2(5):370-9.

Oligodendrocyte adhesion activates protein kinase C-mediated phosphorylation of myelin basic protein.
Vartanian T, Szuchet S, Dawson G, Campagnoni AT.
Science. 1986 Dec 12;234(4782):1395-8.

Regulation of GM2 ganglioside metabolism in cultured cells.
Dawson G, Hancock LW, Vartanian T.
Chem Phys Lipids. 1986 Dec 15;42(1-3):105-16. Review.

The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS.
Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, Rosenberg PA, Volpe JJ, Vartanian T.
J Neurosci. 2002 Apr 1;22(7):2478-86.

Epidermal growth factor receptor induced apoptosis: potentiation by inhibition of Ras signaling.
Högnason T, Chatterjee S, Vartanian T, Ratan RR, Ernewein KM, Habib AA.
FEBS Lett. 2001 Feb 23;491(1-2):9-15.

A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microglia.
Lehnardt S, Henneke P, Lien E, Kasper DL, Volpe JJ, Bechmann I, Nitsch R, Weber JR, Golenbock DT, Vartanian T.
J Immunol. 2006 Jul 1;177(1):583-92.

Failure of spinal cord oligodendrocyte development in mice lacking neuregulin.
Vartanian T, Fischbach G, Miller R.
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):731-5.

Myosin Va controls oligodendrocyte morphogenesis and myelination.
Sloane JA, Vartanian TK.
J Neurosci. 2007 Oct 17;27(42):11366-75.

A clear and present danger: endogenous ligands of Toll-like receptors.
Sloane JA, Blitz D, Margolin Z, Vartanian T.
Neuromolecular Med. 2010 Jun;12(2):149-63. doi: 10.1007/s12017-009-8094-x. Epub 2009 Oct 14. Review.

Growth factor control of CNS myelination.
Park SK, Solomon D, Vartanian T.
Dev Neurosci. 2001;23(4-5):327-37.

Localization of Nogo-A and Nogo-66 receptor proteins at sites of axon-myelin and synaptic contact.
Wang X, Chun SJ, Treloar H, Vartanian T, Greer CA, Strittmatter SM.
J Neurosci. 2002 Jul 1;22(13):5505-15.

Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein.
GrandPré T, Nakamura F, Vartanian T, Strittmatter SM.
Nature. 2000 Jan 27;403(6768):439-44.

Mediation by G proteins of signals that cause collapse of growth cones.
Igarashi M, Strittmatter SM, Vartanian T, Fishman MC.
Science. 1993 Jan 1;259(5091):77-9.

Growth cone transduction: Go and GAP-43.
Strittmatter SM, Valenzuela D, Vartanian T, Sudo Y, Zuber MX, Fishman MC.
J Cell Sci Suppl. 1991;15:27-33. Review.

WAVE1 is required for oligodendrocyte morphogenesis and normal CNS myelination.
Kim HJ, DiBernardo AB, Sloane JA, Rasband MN, Solomon D, Kosaras B, Kwak SP, Vartanian TK.
J Neurosci. 2006 May 24;26(21):5849-59.

Relapses in multiple sclerosis: Relationship to disability.
Goodin DS, Reder AT, Bermel RA, Cutter GR, Fox RJ, John GR, Lublin FD, Lucchinetti CF, Miller AE, Pelletier D, Racke MK, Trapp BD, Vartanian T, Waubant E.
Mult Scler Relat Disord. 2016 Mar;6:10-20. doi: 10.1016/j.msard.2015.09.002. Epub 2015 Sep 8. Review.

Melanoma complicating treatment with natalizumab for multiple sclerosis.
Mullen JT, Vartanian TK, Atkins MB.
N Engl J Med. 2008 Feb 7;358(6):647-8. doi: 10.1056/NEJMc073220. No abstract available.

Development of a novel portable multi-channel near infrared spectroscopy system.
Kostic MN, Vartanian T, Culjat M, Singh R, Grundfest WS.
Stud Health Technol Inform. 2013;184:230-4.

The effects of childhood SNAP use and neighborhood conditions on adult body mass index.
Vartanian TP, Houser L.
Demography. 2012 Aug;49(3):1127-54. doi: 10.1007/s13524-012-0115-y.

The effects of childhood neighborhood conditions on self-reports of adult health.
Vartanian TP, Houser L.
J Health Soc Behav. 2010 Sep;51(3):291-306. doi: 10.1177/0022146510378241.

Treating multiple sclerosis in the natalizumab era: risks, benefits, clinical decision making, and a comparison between North American and European Union practices.
Giovannoni G, Kinkel P, Vartanian T.
Rev Neurol Dis. 2007 Fall;4(4):184-93. Review.

Bacteriologic studies during surgery of the large intestine.
Abolmasov EI, Zhivetskiĭ AV, Enenko IuA, Vartanian TP.
Lab Delo. 1990;(4):67-8. Russian. No abstract available.

Diagnosis of certain intracranial pathological processes in newborn infants by the method of echoencephalography.
Ovakimian ES, Oganesian SS, Vartanian TV, Balaian LA.
Pediatriia. 1976 Jun;(6):23-5. Russian. No abstract available.

Modification of vitamin C content in tubers and surface parts of potato in various conditions of its growth.
Aslanian GS, Vartanian T.
Biokhimiia. 1952 Mar-Apr;17(2):179-85. Russian. No abstract available.