Research Goals
Collaborators
Funding
Techniques used in the lab
Personnel
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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 on 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 are 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 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 neurodegeneration.
Collaborators
Yazen Alnouti, Pharmaceutical Science, UNMC, Omaha, NE
Tatiana Bronich, Center for Drug Delivery and NanoMedicine, Department of Pharmaceutical Sciences
Benson Edagwa, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
Howard S. Fox, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
Harris A. Gelbard, University of Rochester School of Medicine, Rochester, NY
Santhi Gorantla, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
Yutong Liu, Radiology, UNMC, Omaha, NE
Surya Mallapragada, Iowa State University, Ames, IA
JoEllyn McMillan, Pharmacology and Experimental Neuroscience, UNMC Omaha, NE
R. Lee Mosley, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
Balaji Narasimhan, Iowa State University, Ames, IA
Larisa Poluektova, Pharmacology and Experimental Neuroscience, UNMC, Omaha, NE
Scott Shandler, Longevity Biotech, Philadelphia, PA
David Volsky, Icahn School of Medicine at Mount Sinai, New York, NY
Charles Wood, Nebraska Center for Virology, UNL, Lincoln, NE
Funding
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.
Neuroimmunology of Disease Training Program
MPI: Gendelman, H.E. and Monaghan, D.
NIH/NINDS T32 NS105594
This program will provide unique research training experiences in infectious, developmental, and degenerative nervous system diseases. By combining cross-disciplinary team-mentored training in the immune-brain axis, the next generation of neuroscientists will be able to incorporate multidisciplinary approaches into novel research paradigms. This is done to better understand disease processes and develop state-of-the-art diagnostic and therapeutic interventions. The University of Nebraska Medical Center is well positioned to offer this unique cross-disciplinary educational experience.
Chronic HIV infection and Aging in NeuroAIDS (CHAIN) Center
MPI: Buch, S and Fox, H.; Therapeutics Core Leader: Gendelman, H. E.
NIH/NIMH P30 MH062261
This is a Center grant to provide Administrative and Core Support for scientists investigating NeuroAIDS.
SMART HAND
MPI: Gendelman, H. E. and Poluektova, L.
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.
Combined Molecular Excision Therapy (CMET) for Eliminating HIV-1
PI: Gendelman, H.E.
NIH/NIMH R01MH115860-01
CNS Reservoirs of HIV in a Mouse Model of HIV Infection and Cognitive Impairment
PI: Gendelman, H.E.
Icahn School of Medicine at Mount Sinai
This proposal is designed to develop a number of novel anti-retroviral clearance mechanisms to best reduce or perhaps eradicate virus within its brain reservoir. The use of highly active antiretroviral drugs are designed to restrict viral growth as maximally possible and as such best enable viral clearance by immune potentiating and eliminating agents develop by investigators at Mount Sinai Hospital and Medical Center.
Cell Targeted long-acting nanoformulated antiretroviral therapy- (Research Collaboration Agreement-UNeMed)
PI: Gendelman, H.E.
ViiV Healthcare Limited
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.
Long Acting GM-CSF for Parkinson's Disease
PI: Gendelman, H.E.
UNeMed
Novel Kinase and Nanoformulated Protease Inhibitors for Eradication of CNS HIV-1
PI: Gendelman, H.E.
University of Rochester
This proposal is designed to develop a means to eradicate viral infection from its CNS reservoir. The overarching idea is to facilitate crystalline nano formulated antiretroviral drug entry into monocyte-macrophage within late and recycling endosomes by affecting/harnessing phagolysosomal fusion events through the new kinase inhibitor URMC-099. The research is divided equally amongst University of Nebraska and University of Rochester scientists experienced in virology, immunology, pharmacology and neuroscience to pool resources towards a functional HIV-1 cure.
Preclinical Development of LBT-3627, a VPAC2 Agonist with Neuroprotective and Anti-inflammatory Activities in Parkinson's Disease
PI: Gendelman, H.E.
Michael J. Fox
Parkinson's Technology
PI: Gendelman, H.E.
Moderna Therapeutics
Improve the delivery of an immune transformative agent by engagement of a liposomal delivery system for RNA rather than protein in the treatment of Parkinson's disease.
Techniques used in laboratory
- Chimeric Mice
- Fluorescent microscopy
- HIV-1 neurotoxicity assay
- Immunohistochemistry
- Macrophage migration tracking
- Mouse intracerebral stereotactic inoculation
- Mouse models of HIV-1 encephalitis
- Nano-medicine macrophage delivery
- Pathology analysis
- Primary brain and immune cell culture
- Real-time PCR
- Small animal model drug therapy
- Western blotting
- iTRAC and SWATH proteomics
- Flow cytometry/FACS
Personnel
| Aditya Bade, Ph.D. Instructor |
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Mary Banoub Graduate Research Assistant |
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| Denise Cobb Graduate Research Assistant |
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Prasanta Dash, Ph.D. Instructor |
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| Benson Edagwa, Ph.D. Assistant Professor |
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James Hilaire Graduate Research Assistant |
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| Ibrahim Ibrahim Graduate Research Assistant |
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Bhavesh Kevadiya, Ph.D. Instructor |
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| Tanmay Kulkarni Graduate Research Assistant Pharmaceutical Sciences |
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Zhiyi Lin Graduate Research Assistant Pharmaceutical Sciences |
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| Yaman Lu Research Technologist |
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Jatinhumar Pravi Machhi |
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JoEllyn McMillan, Ph.D. |
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Insiya Mukadam |
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| Krista Namminga Research Technician II |
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Kate Olson, Ph.D. |
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| Brendan Ottemann Graduate Research Assistant |
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Lana Reichardt Administrative Associate |
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| Brady Sillman Graduate Research Assistant |
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Bhagya Laxmi Dyavar Shetty Research Technologist, II |
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| Nate Smith Graduate Research Assistant |
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Dhruvkumar Soni |
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| Sruthi Sravanam Research Technologist |
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Hang Su Graduate Research Assistant |
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| Mackenzie Thurston Graduate Assistant-Research Intern |
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Melinda Wojtkiewicz Research Project Specialist |
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