University of Nebraska Medical Center

Laboratory of R. Lee Mosley, PhD

Research 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.

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.

Techniques used in 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


Margaret R. Larson Professor of Internal Medicine and Infectious Diseases
Chair, Department of Pharmacology and Experimental Neuroscience


Laboratory of Howard E. Gendelman, MD

Howard E. Gendelman, MD

Hugh & Jane Hunt Chair in Cancer Research, Eppley Institute for Research in Cancer
Associate Director for Basic Research, Fred & Pamela Buffett Cancer Center


Associate Professor, Department of Radiology
Interim Bioimaging Core Lab Director, Radiology Research Division


Associate Professor


JoEllyn McMillan, PhD

Professor, Eppley Institute


John N. Whitaker Endowed Professor
Professor and Chair, Department of Neurology, University of Alabama at Birmingham

Professor, College of Pharmacy



NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence

PI: H.E. Gendelman; Co-I: R. L. Mosley

Source: NIH/NIDA P01DA028555

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.

Neuroprotective Immunity and HIV Dementia

PI: H. E. Gendelman; Co-I: R. L. Mosley

Source: NIH/NINDS 4R01NS034239

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.

Long Acting GM-CSF for Parkinson's Disease

PI: H.E. Gendelman

Source: UNeMed

Microglial ion channels and HIV-1-associated dementia

PI: H. Xiong; Co-I: R. L. Mosley

Source: NIH/NINDS 4R01NS077873

This grant studies how HIV-1 triggers microglia activation, migration and production of neurotoxins via microglia ion channels, resulting in neuronal damage and ultimately neurological dysfunction.

Leukine (Sargramostim) for Parkinson's Disease

PI: H. E. Gendelman; Co-I: R. L. Mosley

Source: Sanofi U.S. Services, Inc.

These funds were in direct support for a randomized phase I study of Sargramostim in the treatment of Parkinson's disease. Safety and biomarker profiles were a primary research endpoint with clinical and immunological profiling advanced in the quest to improve treatment of motor skills sets during disease.

Nebraska Center for Nanomedicine

PI: T. Bronich; Co-I: R. L. Mosley

Source: 4P20GM103480-09

The program is an interdisciplinary Nanomedicine Center at the University of Nebraska Medical Center. The focus of this program is to develop devices of nanoscale size to improve outcomes for cancer, neurodegenerative diseases, and cardiovascular diseases.

Preclinical Development of LBT-3627, a VPAC2 Agonist with Neuroprotective and Anti-inflammatory Activities in Parkinson's Disease

PI: H. E. Gendelman; Co-I: R. L. Mosley

Source: Michael J. Fox Foundation

The work focuses on establishing proof of concept for the drug LBT-3627 for treatment of Parkinson's disease. We will perform dose and timed responses, evaluate regulatory T cell responses and neuroprotective activities in a range of animal models of human disease.

Parkinson's Technology

PI: H. E. Gendelman; Co-I: R. L. Mosley

Source: Moderna Therapeutics