Dr. Gendelman's Lab

Welcome to Dr. Howard Gendelman's Neuroregeneration Laboratory

Collaborators
Research Goals
Funding
Techniques used in the laboratory
Personnel
Return to Dr. Gendelman's home page
Dr. Gendelman's Biographical Information


Collaborators

Michele Aizenberg, Neurosurgery, University of Nebraska Medical Center (UNMC), Omaha, NE

Mike Boska, Radiology UNMC, Omaha, NE

Tatiana Bronich, Center for Drug Delivery and NanoMedicine, Department of Pharmaceutical Sciences

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, University of Alabama-Birmingham, Birmingham, AL

David Volsky, St. Luke's Roosevelt Hospital, New York, NY

Charles Wood, Nebraska Center for Virology, UNL, Lincoln, NE

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Research Goals

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.

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Funding

SMART HAND
PI: Gendelman, Howard E.
NIH/NIA R01 AG043540
Combination antiretroviral therapy has reduced the mortality and improved the quality of life of human immunodeficiency virus infected people. As people live longer life's quality is often linked to the toxicities of life-long medicines, as such, the means o best identify and predict untoward effects and make newer more effective drugs or drug formulations remains an important research task. This proposal seeks funds to accomplish this through improved disease monitoring, drug development, and pharmacotoxicology approaches.

NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence
PI: Gendelman, H. E.
NIH/NIDA P01 DA028555
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: Gendelman, H. E.
NIH/NINDS NS034239
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.
NIH/NINDS R01 NS036126
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)
NIH/NIMH P01 MH64570
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: Bronich, T; Co-I: Gendelman, H. E.
NIH/NIGMS P20 GM103480
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.

Chronic HIV infection and Aging in NeuroAIDS (CHAIN) Center
PI: Fox, H.; Co-I: Gendelman, H. E.
NIH/NIMH P30 MH062261
This is a Center grant to provide Administrative and Core Support for scientists investigating NeuroAIDS.

T Cell-Mediated Neurodegeneration in Parkinson's Disease
PI: Mosley, R.L; Co-I: Gendelman, H. E.
NIH/NINDS R01 NS070190
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.

An Integrated Immune, Biomaterial and Stem Cell Platform for Neuroprotection and Neuroregeneration Designed to Improve Outcomes for Battlefield Injuries
PI: Bronich T; Co-I:  Gendelman HE
Iowa State University
This grant proposes to develop a T cell delivery system for nanoformulated neural growth factors. The idea is to treat traumatic brain injury with growth factors carried inside regulatory T cells

MCAM Antibodies Effect on Th17 Migration and Neuroprotection in MPTP-Intoxicated Mice
Neotope Biosciences Limited
PI: Gendelman, Howard E.
We seek to develop new means to halt the movement of neurodestructive Th17 cells in Parkinson's disease as a mean to halt disease progression and elicit repaid of a damaged nigrostriatal system in experimental models of human disease

Nebraska Center for Virology
PI: Wood C; Co-I: Gendelman, Howard E.
P30 RR031151
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.

Cell Targeted long-acting nanoformulated antiretroviral therapy (Research Collaboration Agreement-UNeMed)
ViiV Healthcare Limited
PI: Gendelman, Howard E.
These studies aim to develop formulation platforms for a long-acting integrase, a CCR5 inhibitor and a nucleoside reverse transcriptase inhibitor for once monthly therapies with reduced injection volumes and viral reservoir targeting.

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Techniques used in the laboratory

Chimeric Mice Nano-medicine macrophage delivery Flow cytometry/FACS
Fluorescent microscopy Pathology analysis  
HIV-1 neurotoxicity assay Primary brain and immune cell culture  
Immunohistochemistry Real-time PCR  
Macrophage migration tracking Small animal model drug therapy  
Mouse intracerebral stereotactic inoculation Western blotting  
Mouse models of HIV-1 encephalitis iTRAC and SWATH proteomics

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Personnel

Mariluz_Arainga_Ramirez

Mariluz Arainga Ramirez, PhD
Post-Doc Research Associate
m.araingaramirez@unmc.edu

Kathy Estes Kathy Estes
Research Coordinator
kestes@unmc.edu
Christine_Morrison Christine Morrison
Research Technologist I
christine.morrison@unmc.edu
Aditya Bade

Aditya Bade
Graduate Student
Drs. Gendelman, Mike Boska and Yutong Liu's laboratories

aditya.bade@unmc.edu

Reed Felderman Reed Felderman
Administrative Support
reed.felderman@unmc.edu
Prabagaran_Narayanasamy

Praba Narayanasamy, PhD
Instructor
p.narayanasamy@unmc.edu

Hannah_Baldridge

Hannah Baldridge
Research Technologist I
hannah.baldridge@unmc.edu

James_Hilaire

James Hilaire
Graduate Student
james.hilaire@unmc.edu

Katherine_Olson

Kate Olson
Graduate Student
katherine.olson@unmc.edu

Prasanta Dash

Prasanta Dash, PhD
Senior Research Associate
pdash@unmc.edu

Lindsey_Kendrick Lindsey Kendrick
Research Technologist I
lindsey.kendrick@unmc.edu
Pavan_Puligujja

Pavan Puligujja
Graduate Student
pavan.puligujja@unmc.edu

Nicholas_DeKorver2013

Nicholas DeKover
MD/PhD Student
nicholas.dekover@unmc.edu

Tomomi Kiyota Tomomi Kiyota, PhD
Instructor
tkiyota@unmc.edu
Lana_Reichardt

Lana Reichardt
Administrative Assistant
lreichardt@unmc.edu

Shetty_Ravi_Dyavar

Shetty Ravi Dyavar
Instructor

shettyravi.dyavar@unmc.edu

 

Tianyuzi_Li

Tianyuzi Li
Graduate Student
tianyzi.li@unmc.edu

 

Trent_Roberts

Trent Roberts

trent.roberts@unmc.edu

Benson_Edagwa Benson Edagwa
Post Doc Research Associate
benson.edagwa@Wunmc.edu
Xinming Liu

Xinming Liu, PhD
Assistant Professor
xliu@unmc.edu

Brady_Sillman

Brady Sillman
Graduate Student

brady.sillman@unmc.edu

Bret_Elliott Bret Elliott
Research Technologist I
bret.elliott@unmc.edu
Andrea Martinez-Skinner Andrea Martinez-Skinner
Graduate Student
amartinezskinner@unmc.edu
Nate_Smith

Nate Smith
Research Technologist I nathana.smith@unmc.edu

Adrian Epstein Adrian Epstein
MD/PhD Student
aepstein@unmc.edu
Joellyn_McMillan JoEllyn McMillan, PhD
Assistant Professor
jmmcmillan@unmc.edu
Lizhu Wang

Lizhu Wang
Post-Doc Research Associate
lizhu.wang@unmc.edu
        Gang Zhang

Gang Zhang
Graduate Student
gzhang@unmc.edu

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Dr. Gendelman's Biographical Information

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