R. Lee Mosley, Ph.D.

ProfessorLeeMosley

Durham Research Center II 3064
985930 Nebraska Medical Center
Omaha, NE 68198-5930

Phone: 402-559-2510
Email: R. Lee Mosley

Keywords: Immunoregulation, Neurodegeneration, Neuroprotection, Immunology, Vaccine, T cell, Inflammation, Parkinson's disease, MPTP, Amyotrophic Lateral Sclerosis (ALS)


In the News
Professional Summary
Research Interests
Representative Publications
Dr. Mosley's Biographical Information
Visit Dr. Mosley's Laboratory


In the news:

UNMC Today, July 10, 2013
Investigators to launch clinical trial testing Parkinson's therapy

UNMC Newsroom, August 8, 2012
Dr. Mosley on the Joint Research Symposium

YouTube

Dr. Mosley in his own words.


Professional Summary:

Many neurodegenerative diseases exhibit inflammatory components, which have been shown to play integral roles in neurodegenerative processes.

In models of Alzheimer's disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), and experimental allergic encephalitis (EAE, a model for multiple sclerosis), chronic inflammation is a dominant feature, whereas acute inflammatory responses appear essential in murine models for HIV-1-induced encephalitis and Parkinson's disease. In the latter model, dopaminergic-specific neurodegeneration is induced by the dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Proinflammatory cytokines, common to these models as well as responses induced by and type 1 T helper cells (Th1), IL-17A-producing Th cells (Th17), and type 1 cytotoxic T cells (Tc1) responses, exacerbate neurodegenerative processes, whereas suppression of proinflammatory cytokine expression mediated by anti-inflammatory pharmaceuticals or cytokines affords neuroprotection and/or neuroregeneration. Unfortunately, the benefits these modalities are either transient or subjects become refractory to therapy.

Our objective is to develop vaccine strategies that induce and sustain type 2 or type 3 anti-inflammatory T cell (Th2 and Th3) or regulatory T cell (Treg) responses, which interdict proinflammatory processes with subsequent amelioration of neurodegenerative processes and promotion of neuroprotection and/or neuroregeneration. Strategies for neuroprotective vaccines are proposed that preferentially mediate anti-inflammatory responses.

In our animal models, monitoring of disease progression or regression is afforded by noninvasive analyses using single photon emission computed tomography (SPECT), magnetic resonance (MR), and MR spectroscopic (MRS) imaging. Combined with conventional immunological assessment, sera and immune cell or neuronal tissue products from vaccinated subjects are evaluated for normal or unique cytokine profiles by proteomic analysis that collectively utilized new technologies of protein chip adsorption, surface enhanced laser desorption/ionization (SELDI) mass spectroscopy, and ion-trap mass spectroscopy-based protein sequencing. Together, novel vaccine strategies with higher resolution assessment of vaccine efficacies will facilitate greater translational potentials for future therapeutic modalities.

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Research Interests:


Representative Publications:

  1. Gendelman HE, Mosley RL, Boska MD, McMillan J. (2014) The promise of nanoneuromedicine. Nanomedicine (Lond) 9(2): 171-6. PMID: 24552556
  2. Klyachko NL, Haney MJ, Zhao Y, Manickam DS, Mahajan V, Suresh P, Hingtgen SD,Mosley RL, Gendelman HE, Kabanov AV, Batrakova EV. (2014) Macrophages offer a paradigm switch for CNS delivery of therapeutic proteins. Nanomedicine (Lond) 9(9) 1403-22. PMID: 24237263
  3. Kosloski LM, Kosmacek EA, Olson KE, Mosley RL, Gendelman HE. (2013) GM-CSF induces neuroprotective and anti-inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxicated mice. J Neuroimmunol 265(1-2): 1-10. PMID: 24210793
  4. Heinrichs-Graham E, Wilson TW, Santamaria PM, Heithoff SK, Torres-Russotto D, Hutter-Saunders JA, Estes KA, Meza JL, Mosley RL, Gendelman HE. (2014) Neuromagnetic evidence of abnormal movement-related Beta desynchronization in Parkinson's disease. Cereb Cortex 24(10):2669-78. PMID: 23645717
  5. Haney MJ, Zhao Y, Harrison EB, Mahajan V, Ahmed S, He Z, Suresh P, Hingtgen SD, Klyachko NL, Mosley RL, Gendelman HE, Kabanov AV, Batrakova EV. (2013) Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases. PLoS One 8(4): e61852. PMID: 23620794
  6. Saunders JA, Estes KA, Kosloski LM, Allen HE, Dempsey KM, Torres-Russotto DR, Meza JL, Santamaria PM, Bertoni JM, Murman DL, Ali HH, Standaert DG, Mosley RL, Gendelman HE. (2012) CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson's disease. J Neuroimmune Pharmacol 7(4) 927-38. PMID: 23054369
  7. Dash PK, Gendelman HE, Roy U, Balkundi S, Alnouti Y, Mosley RL, Gelbard HA, McMillan J, Gorantla S, Poluektova LY. (2012) Long-acting nanoformulated antiretroviral therapy elicits potent antiretroviral and neuroprotective responses in HIV-1-infected humanized mice. AIDS 26(17): 2135-44. PMID: 22824628
  8. Roy U, McMillan J, Alnouti Y, Gautum N, Smith N, Balkundi S, Dash P, Gorantla S, Martinez-Skinner A, Meza J, Kanmogne G, Swindells S, Cohen SM, Mosley RL, Poluektova L, Gendelman HE. (2012) Pharmacodynamic and antiretroviral activities of combination nanoformulated antiretrovirals in HIV-1-infected human peripheral blood lymphocyte-reconstituted mice. J Infect Dis 206(10): 1577-88. PMID: 22811299
  9. Stone DK, Kiyota T, Mosley RL, Gendelman HE. (2012) A model of nitric oxide induced α-synuclein misfolding in Parkinson's disease. Neurosci Lett 523(2): 167-73. PMID: 22776646
  10. Mosley RL, Hutter-Saunders JA, Stone DK, Gendelman HE. (2012) Inflammation and adaptive immunity in Parkinson's disease. Cold Spring Harb Perspect Med 2(1): a009381. PMID: 22315722

Additional publications in PubMed.


Dr. Mosley's biographical information
Visit Dr. Mosley's laboratory
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