Dr. Mosley's Lab

Welcome to Dr. R. Lee Mosley's laboratory

Collaborators
Research Goals
Funding
Techniques used in the laboratory
Personnel
Return to Dr. Mosley's home page
Dr. Mosley's biographical information


Collaborators

Howard E. Gendelman, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
Michael Boska, Radiology, UNMC, Omaha, NE
Elena Batrakova, Pharmaceutical Sciences, UNMC, Omaha, NE
David George Standaert, Neurology, University of Alabama, Birmingham, AL
David McMillian, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
JoEllyn McMillian, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
Dong Wang, Pharmaceutical Sciences, UNMC, Omaha, NE
Pawel Ciborowski, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
M.A. (Tony) Hollingsworth, Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE
Joyce Solheim, Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE

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Research Goals

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

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Funding

T Cell-Mediated Neurodegeneration in Parkinson's Disease
PI: Mosley, R. Lee
NIH/NINDS
This grant proposes to elucidate the role of T cell-mediated immunity in the pathogenesis of disease progression in a murine model of Parkinson's disease. We hypothesize that the tempo and progression of PD is accelerated by N-a-syn stimulation of microglia and APCs, recognition by the adaptive immune system of neoantigenic epitopes on N-a-syn, and induction of effector T cells (Teffs) that extravasate to neuroinflammatory sites, exacerbate inflammatory microglia, and augment microglia-mediated neurotoxicity. To test our hypothesis, 3 proposed aims will determine 1) the N-a-syn epitopes and MHC elements permissive for induction of T helper cells that mediate dopaminergic neurodegeneration, 2) N-a-syn-specific T helper effector subset(s) responsible for exacerbated neurodegeneration, and 3) molecular and biochemical mechanisms by which N-a-syn specific Teff subset(s) modulate neurodegeneration.

Nanomedicine and NeuroAIDS
PI: Gendelman, Howard E
Co-I: Mosley, R. Lee
NIH-NINDS
This research proposes to investigate the biophysiological properties of monocytes and monocyte-derived macrophages that influence cell migration both across the blood-brain barrier and within the brain. The central hypothesis is that changes in ion channel expression in monocytes and macrophages following exposure to virus and immune products influences the cell's ability to change its volume and shape, thus influencing cell migration. Such events are pivotal for macrophages to enter the brain and to secrete the toxins that underlie the neuropathogenesis of HIV-1 associated dementia.

NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence
PI: Gendelman, Howard E.
Co-I: Mosley, R. Lee
NIH/NIDA
This is an integrative cross approach translational and multi-investigator program grant seeking to develop nanoformulated antiretroviral drug therapy from the bench to the patient.

Inflammatory Cells for Transport of Therapeutic Polypeptides Across the BBB
PI: Batrakova, E
Co-I: Mosley, R. Lee
NIH/NINDS
Currently, there are no curative or interdictive therapies available for Parkinson's disease (PD), and only palliative therapies such as replacement strategies for missing neurotransmitters exist. The main obstacle is the blood brain barrier (BBB) that severely limits the brain penetration of therapeutics, which can be successfully used for PD therapy. In particular, BBB is practically impermeable for polypeptides involved in anti-inflammatory neuroprotection. Nevertheless, there is a class of inflammatory response cells that have extraordinary ability to cross the BBB due to their increased margination and extravasation. A long-term objective of this proposal is to develop a targeted cell-mediated delivery of therapeutic polypeptides to the brain to attenuate neuroinflammation and produce neuroprotection in patients with PD.

Neuroprotective Immunity and HIV Dementia
PI: Gendelman, Howard E.
Co-I: Mosley, R. Lee
NIH/NINDS
This proposal will determine cell responses in macrophages following HIV-1 infection and engagement with T cells and T cell subsets. Macrophage functions including phagocytosis, antigen presentation, intracellular killing and effector cell responses and their modulation by T cells is a focus for this work. Signal transduction pathways and mechanisms for virus-induced neurotoxicity or neuroprotection will be developed.

Scripps NeuroAIDS Preclinical Studies (SNAPS)
PI: Fox, Howard
Co-I: Mosley, R. Lee
NIH/NIMH
This is a Center grant to provide Administrative and Core Support for scientists investigating NeuroAIDS.

Voltage-gated K Channels, Microglia and HIV Dementia
PI: Xiong, Huangui
Co-I: Mosley, R. Lee
NIH/NINDS
This grant proposes to study how HIV-1-infected macrophages alter neuronal voltage-gated K (Kv) channels, leading to neuronal dysfunction and cognitive decline. How the “diseased” neurons affect macrophage secretory activity is another focus of this grant. The goals of the proposed studies are to understand HIV-1-associated channelopathies that cause neuronal dysfunction or death and to find potential ways to reverse and/or prevent HIV-1-induced neuronal damage.

Regenerative Therapy of Parkinson's Disease by iPS Cells
PI: Zheng, Jialin
Co-I: Mosley, R. Lee
NE-DHHS
In this application we purpose to develop induced pluripotent stem (iPS) cells from easily accessible cells and address the potential of using iPS cells as a therapeutic strategy to treat a mouse model of Parkinson's disease (PD).

Nebraska Center for Nanomedicine
PI: Kabanov, Alexander
Co-I: Mosley, R. Lee
This proposal seeks to develop an interdisciplinary Nanomedicine Center at the University of Nebraska Medical Center (UNMC). The focus of this proposal is to develop the means to best use devices of nanoscale size to improve outcomes for cancer, neurodegenerative and cardiovascular diseases.

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Techniques used in the laboratory

  • Mouse models of Parkinson's disease and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease)
  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD
  • Immunization and adoptive transfer of T cell immunity
  • In vitro assays of T cell and innate immune function
  • Magnetic-activated cell sorting (MACS)
  • Flow cytometry and fluorescence-activated cell sorting (FACS)Immunohistochemical analysis
  • Stereological and densitometric analyses
  • Fluorescent confocal microscopy
  • Bioimaging: X-ray computer-aided tomography/single photon emission computed tomography (CT/SPECT), magnetic resonance/spectroscopic imaging (MRSI)
  • Assays for T cell and myeloid cell migration
  • RNA and protein arrays
  • Proteomics, 2D-DIGE, SILAC and iTRAQ
  • Western blotting
  • Real-time PCR

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Personnel

Kristi_Anderson

Kristi Anderson
Graduate Student

kristi.anderson@unmc.edu

 

 

 

Max_Kuenstling

Max Kuenstling
Graduate Student

mkuenstling@unmc.edu

   
Charles_Schutt_2012

Charles Schutt
Graduate Student

charles.schutt@unmc.edu

   
Adam_Szlachetka

Adam Szlachetka
Research Technologist

amszlachetka@unmc.edu

 

 

 

 Rebecca_Wilshusen_2012

Rebecca Wilshusen
Graduate Student

rebecca.wilshusen@unmc.edu

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Return to Dr. Mosley's home page
Dr. Mosley's biographical information

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