Welcome to Dr. Howard Gendelman's Neuroregeneration Laboratory
Michele Aizenberg, Neurosurgery, University of Nebraska Medical Center (UNMC), Omaha, NE
Mike Boska, Radiology UNMC, Omaha, NE
R. Lee Mosley, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
Stephen Dewhurst, University of Rochester, Rochester, NY
Harris Gelbard, University of Rochester School of Medicine, Rochester, NY
Edmundo Kraiselburd, University of Puerto Rico, San Juan, PR
Serge Przedborski, Columbia University, New York, NY
David George Standaert, Univ. Alabama-Birmingham, Birmingham, AL
David Volsky, St. Luke's Roosevelt Hospital, New York, NY
Charles Wood, Nebraska Center for Virology, UNL, Lincoln, NE
The long-range goals of the laboratory are to develop immunopharmacological approaches to improve the diagnosis and treatment options for neurodegenerative diseases that include HIV-1 associated neurocognitive disorders (HAND) and Parkinson's disease (PD).
The laboratory initiative is divided into specific programs, each co-headed by an experienced scientist. Specific expertise in immunology, molecular biology, infectious disease, proteomics, physiology and pathogenesis is provided to the student and research fellow.
First, studies revolving around the development of nanoformulated cell-based drug delivery with a special focus to the CNS. Nanotoxicology studies involve the studies of the regulation of leukocyte entry into peripheral and neural tissues with a focus on glial immunity. This is seen during neurodegenerative diseases and include studies of HAND and PD. Those that are being developed include, but are not limited to, antiretroviral, neuroprotective, and anti-inflammatory drugs.
Second, drug testing (neuroprotective and neuroregenerative) and improved diagnostics for HAND is being developed in virus-infected immunodeficient mice. This program is part of national grant efforts that involve scientists at the University of Nebraska Medical Center, the University of Rochester, and Columbia University College of Physicians and Surgeons. The focus is to perform translational research that would move quickly from animals to humans.
Third, proteomic and metabolomic approaches for biomarker discovery are linked to studies of cell-cell interactions for disease. This is part of a broader initiative in studies of how drugs of abuse influence viral replication and immune dysregulation.
Fourth, neuroimmunologic and vaccine approaches that induce protective immunity and neuroregeneration are being pursued in animal models of HAND, PD and amyotrophic lateral sclerosis. The laboratory has developed a unique immunization approach that uses the immune system as a cell source for brain repair during neurodegenerative.
NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence
PI: Gendelman, H. E.
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.
Neural Immunity in HIV Dementia
PI: Gendelman, H. E.
The major goal of this grant is the study of the specific immunologic basis of HAD and linkages between it and other neurodegenerative disorders. This grant brings together in one organizational structure a group of scientists with expertise in areas of neurotoxicology, cellular immunology, neuropathology, neurophysiology, neuropharmacology and molecular biology, who maintain a unified focus on how MP biology affects both neurodegeneration and neuroprotection.
Neuroprotective Immunity and HIV Dementia
PI: Gendelman, H. E.
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.
Nanomedicine and NeuroAIDS
PI: Gendelman, H. E.
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.
Targeted Neuroprotection for HIV-1 Associated Neurologic Disease
PI: Gelbard, H.; Project 2 Leader: Gendelman, H. E. (Project 2: Novel Adjunctive Therapies for NeuroAIDS)
The purpose of this core is to assist in the design of adjunctive therapeutic strategies for treatment and/or prevention of neurologic disease following human immunodeficiency virus type-one (HIV-1) infection. In this regard, purified human monocyte-derived macrophages (MDM) and MDM conditioned media (MCM) will be supplied, following HIV-1 infection and/or immune activation, to all investigators on request, within the Rochester Cooperative NeuroAIDS Drug Discovery Group (RCNDDG). In addition, promising anti-inflammatory and/or neuroprotective drugs, developed in laboratory assays or proposed, will be tested for therapeutic efficacy in a severe combined immune deficiency (SCID) mouse model of HIV-1 encephalitis (HIVE).
Nebraska Center for Nanomedicine
PI: Kabanov, A.; Co-I: Gendelman, H. E.
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.
Cellular Mechanisms for HIV-1 Induced Neuronal Injury
PI: Wood, C; Co-Director: Gendelman H. E.
The major goals of this grant are to develop a comprehensive center for the study of viral diseases headquartered in Lincoln Nebraska. This is a combined and shared initiative between the University of Nebraska at Lincoln, Creighton University and the University of Nebraska Medical Center. The moneys are used solely for developing new investigators and for recruitment.
Scripps NeuroAIDS Preclinical Studies (SNAPS)
PI: Fox, H.; Project 1 Leader: Gendelman, H. E.
This is a Center grant to provide Administrative and Core Support for scientists investigating NeuroAIDS.
Proteomic Strategies for AIDS and Drug Abuse - HIV and METH CNS Synergy
PI: Fox, H.; Project Leader: Gendelman, H. E.
The aims of the Program Project are to develop and use proteomic strategies to uncover the aspects of methamphetamine, HIV-1 and glial crosstalk (Project 1), methamphetamine and the neuropathogenesis of SIV infection (Project 2), and biomarkers in an HIV-1 infected drug abusing clinical cohort (Project 3).
T Cell-Mediated Neurodegeneration in Parkinson's Disease
PI: Mosley, R.L; Co-I: Gendelman, H. E.
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.
Biomarkers and Immunotherapy for Parkinson's Disease
PI: Gendelman, H. E.
Michael J. Fox Foundation
This grant seeks to develop a diagnostic biomarker for Parkinson's disease. Its research foundation rests in studies performed in murine models of human disease demonstrating that deficits in CD4+ T cell subsets underlie nigrostriatal degeneration. We wish to test this hypothesis in humans with Parkinson's disease. The work will be a basis for future clinical phase I studies for immunization strategies designed to protect nigral neurons against the ravages of neuronal degeneration.
|Chimeric Mice||Nano-medicine macrophage delivery|
|Fluorescent microscopy||Pathology analysis|
|HIV-1 neurotoxicity assay||Primary brain and immune cell culture|
|Macrophage migration tracking||Small animal model drug therapy|
|Mouse intracerebral stereotactic inoculation||Western blotting|
|Mouse models of HIV-1 encephalitis|