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Center for Neurodegenerative and Neuroimmunologic Diseases

The Center’s mission is to promote translational research and to foster the application of a wide range of current biological methods for the objective of elucidating the pathogenesis of and developing novel therapies for certain chronic incurable neurological conditions, with a particular emphasis on Parkinson’s disease (PD) and Multiple Sclerosis (MS). Specific goals in PD include the conduct of basic research in the molecular pathogenesis of the disease with a focus on the role of genetic mutations in protein aggregation and neuronal cell death, the identification of targets for therapeutic interventions, and testing those targets in animal models. In MS, research projects focus on immunopathogenesis using animal models, mechanisms of action of MS therapies, identification of biomarkers of treatment response, and developing strategies to deliver therapeutic genes into the brain using bone marrow cells as vehicles.

The educational goals of the Center are to provide an environment for training graduate students, post-doctoral fellows and physician scientists in neurodegenerative and neuroimmunological diseases, and to provide elective time for undergraduates, medical students, and neurology residents or trainees from other departments who wish to explore research opportunities in neurologic diseases.

group

Faculty:

  • M. Maral Mouradian, MD, Center Director, William Dow Lovett Professor of Neurology
  • Suhayl Dhib-Jalbut, MD, Professor and Chairman, Department of Neurology
  • Konstantin E. Balashov, MD, PhD, Associate Professor of Neurology
  • Eunsung Junn, PhD, Assistant Professor of Neurology
  • Kouichi Ito, PhD, Associate Professor of Neurology

Postdoctoral Fellows:

  • Amrita Datta-Chaudhuri, PhD
  • Doo-Chul Choi, PhD
  • Eunsu Park, PhD
  • Hye-Jin Park, PhD
  • Sudhir Yadav, PhD
  • Run Yan, PhD

Postdoctoral Alumni:

  • Sridhar Boppana, PhD
  • Yoon-Jee Chae, PhD
  • Tae-ho Chung, PhD
  • Vera Dias, PhD
  • Liqiang He, PhD
  • Hui Huang, PhD
  • Joo-Young Im, PhD
  • Won-Hee Jang, PhD
  • Byeong Seon Jeong, PhD
  • Kang-Woo Lee, PhD
  • Zeqian Mo, PhD
  • Vinicius Pascoal, PhD
  • Sebastian Rodriguez, PhD
  • Reuben Valenzuela, MD
  • Jong-Minn Woo, PhD

 

Research Specialists:

  • Latt Latt Aung, MD
  • Naoko Ito, BS

Graduate Students:

  • Stephanie Oh
  • Hilary Grosso, (PhD 2012)

 

Former Graduate Students:

  • William McGinty
  • Anuschka Bhatia
  • Nicole Hartmann

Administrative Staff:

  • Sheila Reaves - Program Support Specialist

 

Selected Publications from Center Investigators:

Junn E, Lee SS, Suhr UT and Mouradian MM. Parkin Accumulation in Aggresomes due to Proteasome impairment. J. Biol. Chem., 277(49): 47870-47877, 2002.

Lee G, Junn E, Tanaka M, Kim YM, Lee SS, and Mouradian MM. Synphilin-1 degradation by the ubiquitin-proteasome pathway and effects on cell survival. J. Neurochem. 83(2): 346-352, 2002.

Lee, G., Junn, E., Tanaka, M., Kim, Y.M., Lee, S.S., Mouradian, M.M.: Synphilin-1 degradation by the ubiquitin- proteasome pathway and effects on cell survival. J. Neurochem., 83:346-352, 2002.

Junn, E., Mouradian, M.M.: Human a-synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neurosci. Lett., 320:146-150, 2002.

Dunah, A.W., Jeong, H., Griffin, A., Kim, Y.-M., Hersch, S.M., Mouradian, M.M., Young, A.B., Tanese, N., Krainc, D.: Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science, 296:2238-2243, 2002.

Junn E, Ronchetti RD, Quezado MM, Kim SY, Mouradian MM.. Tissue transglutaminase- induced aggregation of {alpha}-synuclein: Implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci USA. 100(4): 2047-2052, 2003.

Lee SS, Kim YM, Junn E, Lee G, Park KH, Tanaka M, Ronchetti RD, Quezado MM, Mouradian MM. Cell cycle aberration by a-Synuclein over-expression and cyclin B immunoreactivity in Lewy bodies. Neurobiology of Aging, 24(5): 687-696, 2003.

Junn, E., Ronchetti, R.D., Quezado, M.M., Kim, S.-Y., Mouradian, M.M.: Tissue transglutaminase-induced aggregation of a-synuclein: Implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA, 100(4):2047-2052, 2003.

Quandt J.A., Baig M., Yao K., Kawamura K, Huh J., Ludwin S., Bian H.J., Bryant M., Quigley L., Nagy Z., McFarland H.F., Muraro P.A., Martin R., and Ito K. Unique Phenotypic Clinical and Pathological Features in HLA-DRB1*0401-restricted MBP111-129-specific Humanized TCR Tg mice. J. Exp. Med. 2004; 200: 223-234.

Huh J., K. Yao, L. Quigley, McFarland., H.F. Muraro, P.A.. Martin, R., and Ito K. Limited repertoire of HLA-DRB1*0401-restricted MBP111-129 specific T cells in HLA-DRB1*0401 Tg mice and their pathogenic potential. J. Neuroimmunol. 2004; 151: 94-102.

Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T and Mouradian MM. Aggresomes formed by a-Synuclein and Synphilin-1 are cytoprotective. J. Biol. Chem,. 279(6): 4625-4631, 2004.

Lee G, Tanaka M, Park K, Lee SS, Kim YM, Junn E Lee SH and Mouradian MM. Casein kinase II phosphorylation regulates Synphilin-1/a-Synuclein interaction and inclusion body formation. J. Biol. Chem., 279(8): 6834-6839, 2004.

Makar, T.K., Trisler, D., Eglitis, M.A., Mouradian, M.M., Dhib-Jalbut, S.: Brain-derived neurotrophic factor (BDNF) gene delivery into the CNS using bone marrow cells as vehicles. Neurosci. Lett. 356:215-219, 2004.

Lee, G., Tanaka, M., Park, K., Lee, S.S., Kim, Y.M., Junn, E., Lee, S.H., Mouradian, M.M.: Casein kinase II mediated phosphorylation regulates a-synuclein / synphilin-1 interaction and inclusion body formation. J. Biol. Chem., 279(8):6834-6839, 2004.

Dhib-Jalbut, S., Mouradian, M.M.: Delivery of transgenically modified adult bone marrow cells to the rodent central nervous system. Expert Opin. Biol. Th., 4(5):669-675, 2004.

Junn E, Taniguchi H, Jeong BS, Zhao X, Ichijo H and Mouradian MM. Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase activity and cell death. Proc. Natl. Acad. Sci. USA. 102(27): 9691-9696, 2005.

Dhib-Jalbut, S. Pathogenesis of Myelin/Oligodendrocyte damage in Multiple Sclerosis. Neurology 68(suppl3):S13-S21, 2007.

Park KA, Byun HS, Won M, Yang KJ, Shin S, Piao L, Kim JM, Woon WH, Junn E, Park J, Seok JH, Hur GM. Sustained activation of protein kinase C down-regulates nuclear factor-{kappa}B signaling by dissociation of IKK-{gamma} and Hsp90 complex in human colonic epithelial cells. Carcinogenesis 28(1): 71-80, 2007.

Kawamura K., Yao K., Shukaliak-Quandt JA , Huh J., Baig M., Quigley L., Ito N., Necker A., McFarland HF, Muraro PA, Martin R, and Ito K. Different development of MBP agonist- and antagonist-specific human TCR Tg T cells in the thymus and periphery. J. Immunology 2008; 181(8): 5462-72.

Makar MK, Trisler D, Bever CT, Goolsby JE, Sura KT, Balasubramanian S, Sultana S, Patel N, Ford D, Singh IS, Gupta A, Valenzuela RM, Dhib-Jalbut SS. Stem cell-based delivery of IFN-B reduces relapses in Experimental Autoimmune Encephalomyelitis. J Neuroimmunology, 196:67-81, 2008.

Mochizuki, H., Yasuda, T., Mouradian, M.M.: Advances in gene therapy for movement disorders. Neurotherapeutics, 5(2):260-269, 2008.

Freedman M, Cohen B, Dhib-Jalbut S, Jeffrey D, Reder A, Sandberg-Wolheim M, Weinstock-Guttman B. Recognizing and treating suboptimally controlled multiple sclerosis: steps toward regaining command. Current Medical Research & Opinion, 25:2459-2470, 2009.

Junn E, Jang WH, Zhao X, Jeong BS and Mouradian MM. Mitochondrial Localization of DJ-1 Leads to Enhanced Neuroprotection. J. Neurosci. Res. 87(1): 123-129, 2009.

Junn E, Lee KW, Jeong BS, Chan TW, Im JW and Mouradian MM. Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc. Natl. Acad. Sci. USA. 106(31):13052-7, 2009.

Lee, S.H., Jang, M.K., Kim, O.S., Lee, O.H., Kim, N.Y., Yoo, K.H., Lee, D.G., Shong, Y.H., Mouradian, M.M.: Activation of the GDNF-Inducible Transcription Factor (GIF) Gene Promoter by Glucocorticoid and Progesterone. J. Steroid Biochem. Mol. Biol., 115(1-2):30-35, 2009.

Graber J, Dhib-Jalbut S. Protective immunity in the nervous system. Pharmacology & Therapeutics, 121:147-59, 2009.

Balashov, K.E., Pal, G., and M.L. Rosenberg. Optic neuritis incidence is increased in spring months in patients with asymptomatic demyelinating lesions. Multiple Sclerosis 16: 252-4, 2010.

Aung, L.L., Fitzgerald-Bocarsly, P., Dhib-Jalbut, S., and K. E. Balashov, Plasmacytoid dendritic cells in multiple sclerosis: Chemokine and chemokine receptor modulation by interferon-beta. J Neuroimmunol 226(1-2):158-64, 2010.

Balashov,K.E., Aung, L.L., Vaknin-Dembinsky, A., Dhib-Jalbut, S., Weiner, H.L. Interferon-beta inhibits Toll-like receptor 9 processing in multiple sclerosis. Ann Neurol, 68: 899-906, 2010.

Dhib-Jalbut S, Marks S. Interferon-B mechanisms of action in multiple sclerosis. Neurology 74:S17-24, 2010.

Dhib-Jalbut S. Guest Editor, Multiple Sclerosis Disease-Modifying Therapies: Mechanisms of Action and Practical Implications. Neurology, V74, Supplement 1, 2010.

Graber J, McGraw CA, Kimbrough D, Dhib-Jalbut S. Overlapping and distinct mechanisms of action of multiple sclerosis therapies. Clinical Neurology and Neurosurgery. Clin Neurol Neurosurg; 112(7):583-91, 2010.

Im JY, Lee KW, Junn E and Mouradian MM. DJ-1 Protects Against Oxidative Damage by Regulating the Thioredoxin/ASK1 Complex. Neuroscience Res. 67(3): 203-8, 2010.

Lee EJ, Woo MS, Moon PG, Baek MC, Choi IY, Kim WK, Junn E and Kim HS. a-Synuclein Activates Microglia by Inducing the Expressions of Matrix Metalloproteinases and the Subsequent Activation of Protease-Activated Receptor-1. J. Immunol. 185(1): 615-23, 2010.

Junn, E., Mouradian, M.M.: microRNAs in neurodegenerative disorders. Cell Cycle, 9(9):1717-1721, 2010.

Cao, X., Yasuda, T., Uthayathas, S., Ray L. Watts, R.L., Mouradian, M.M., Mochizuki, H., Papa, S.M.: Striatal overexpression of DeltaFosB reproduces chronic levodopa-induced involuntary movements. J. Neurosci., 30(21):7335-7343, 2010.

Longhini, A.L.F., Glehn, F., Brand√£o, C.O., dePaula, R.F.O., Pradella, F., Moraes. A.S., Farias, A.S., Oliveira, E.C., Quispe-Cabanillas, J.G., Abreu, C.H., Damasceno, A., Damasceno, B.P., Balashov, K.E., and L.M.B. Santos. Plasmacytoid Dendritic Cells are increased in Cerebrospinal Fluid of Untreated Patients during Multiple Sclerosis Relapse. J Neuroinflammation 8 (2): 1-4, 2011.

Graber J and Dhib-Jalbut S. Biomarkers in Multiple Sclerosis. J Neurological Sciences 305:1-10, 2011.

Lee K-W, Chen W, Junn E, Im J-Y, Grosso H, Sonsalla PK, Feng X, Ray N, Fernandez JR, Chao Y, Masliah E, Voronkov M, Braithwaite SP, Stock JB and Mouradian MM. Enhanced phosphatase activity attenuates alpha-synucleinopathy in a mouse model. J. Neurosci. 31(19):6963-71, 2011.

Kim YM, Jang WH, Quezado MM Oh Y, Chung KC, Junn E and Mouradian MM. Proteasome inhibition induces a-Synuclein SUMOylation and Aggregate formation. J. Neurological Sciences 307(1-2):157-61, 2011.

Oh, Y., Kim, Y.M., Mouradian, M.M., Chung, K.C.: Human Polycomb protein 2 promotes a-synuclein aggregate formation through covalent SUMOylation. Brain Res., 1381:78-89, 2011.

Aung L.L, Brooks, A., Greenberg, S.A., Rosenberg, M.L., Dhib-Jalbut, S., and K.E. Balashov. Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells. J Neuroimmunol., 250: 99-105, 2012.

Glehn, F., Santos, L.M., and K.E. Balashov: Plasmacytoid dendritic cells and immunotherapy in multiple sclerosis. Immunotherapy 4(10): 1053-61, 2012.

Junn, E., Mouradian, M.M.: MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol. Therap., 133(2):142-150, 2012.

Lee KW, Zhao X, Im JY, Grosso H, Jang WH, Chan TW, Sonsalla PK, German DC, Ichijo H, Junn E, Mouradian MM. Apoptosis Signal-Regulating Kinase 1 Mediates MPTP Toxicity and Regulates Glial Activation. PLoS One. 7(1):e29935, 2012.

Grosso, H., Mouradian, M.M.: Transglutaminase 2: Biology, relevance to neurodegenerative diseases and therapeutic implications. Pharmacol. Therap., 133(3):392-410, 2012.

Braithwaite, S.P., Stock, J.B., Mouradian, M.M.: a-Synuclein phosphorylation as a therapeutic target in Parkinson’s disease. Rev. Neurosci., 23(2):191-198, 2012.

Mouradian, M.M.: MicroRNAs in Parkinson's disease. Neurobiol. Dis., 46:279-284, 2012.

Braithwaite, S.P., Voronkov, M., Stock, J.B., Mouradian, M.M.: Targeting phosphatases as the next generation of therapeutics for neurodegenerative disorders. Neurochem. Int., 61(6):899-906, 2012.

Im, J.-Y., Lee, K.-W., Woo, J.M., Junn, E., Mouradian, M.M.: DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway. Hum. Mol. Genet. 21(13):3013-3024, 2012.

Quandt J.A., Huh J., Baig M., Yao K., Ito N., Bryant M., Kawamura K., Pinilla C., McFarland H.F., Martin R., Ito K: Myelin Basic Protein-Specific TCR/ HLA-DRB5*01:01 Transgenic Mice Support the Etiologic Role of DRB5*01:01 in Multiple Sclerosis. J. Immunology; 89(6):2897-908, 2012.

Dhib-Jalbut S, Sumandeep S, Valenzuela RM, Ito K, Patel P, Rametta M. Immune response during Interferon-beta-1b treatment in patients with multiple sclerosis who experienced relapses and those who were relapse free in the START study. J neuroimmunol. 254:131- 140, 2013.

Dhib-Jalbut S, Valenzuela RM, Ito K, Kaufman M, Picone MA, Buyske S. HLA DR and DQ alleles and Haplotypes associated with clinical response to Glatiramer Acetate in multiple Sclerosis. Multiple Sclerosis and Related Disorders. 2:340-348, 2013.

Huang H, Ito K, Dangond F, Dhib-Jalbut S. Effect of interferon beta-1a on B7.1 and B7.2 B-cell expression and its impact on T-cell proliferation. J Neuroimmunol., 258(1-2):27-3, 2013.

Lee. K.-W., Im, J.-Y., Woo, J.-M., Grosso, H., Kim, Y.-S., Cristovao, A.C., Sonsalla, P.K., Schuster, D.S., Jalbut, M.M., Fernandez, J.R., Voronkov, M., Junn, E., Braithwaite, S.P., Stock,  J.B., Mouradian, M.M.: Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson’s disease. Neurotherapeutics, 10:143-153, 2013.