Dr. Gendelman's Laboratory

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.

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Collaborators

Yazen Alnouti, Pharmacuetical 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

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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.

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.

SMART HAND
MPI: Gendelman, H. E. and Poluektova, Larisa
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.

Leukine (Sargramostim) for Parkinson's Disease
PI: Gendelman, H.E.
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.

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.

Novel Kinase and Nanoformulated Protease Inhibitors for Eradication of CNS HIV-1
PI: Gendelman
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.

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Techniques used in laboratory

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Personnel

Aditya Bade, Ph.D.
Instructor
Aditya Bade Mary Banoub
Graduate Student
Mary Banoub
Denise Cobb
Graduate Student
Denise Cobb Prasanta Dash, Ph.D.
Instructor
pDash
Rinku Dutta, Ph.D.
Research Instructor
Rinku Dutta Bhagya Laxmi Dyavar Shetty, M.S.
Research Technologist II
Bhagya Laxmi Dyavar Shetty
Benson Edagwa, Ph.D.
Assistant Professor
Benson Edagwa James Hilaire
Graduate Student
jHilaire
Ibrahim Ibrahim
Graduate Student
Ibrahim Ibrahim Bhavesh Kevadiya, Ph.D.
Post Doctoral Fellow
Bhavesh Kevadiya
Zhiyi Lin
Graduate Student
Zhiyi Lin Yaman Lu
Research Technologist
Yaman Lu
Jatinhumar Pravi Machhi
Post-Doctoral Fellow
Jatin Machhi

JoEllyn McMillan, Ph.D.
Associate Professor

JoEllyn McMillan, Ph.D.
Krista Namminga
Hourly Worker
Krista Namminga

Andrew Nguyen
Other Hourly Worker

Andrew Nguyen
Saumya Nigam, Ph.D.
Post-Doctoral Fellow
Saumya Nigam Kate Olson
Graduate Student
Kate Olson
Brendan Ottemann
Graduate Research Assistant
Brendan Ottemann Celina Prince
Other hourly worker
Celina Prince
Lana Reichardt
Administrative Associate
lReichardt Brady Sillman
Graduate Student
bSillman
Nate Smith
Graduate Student
nSmith Hang Su
Graduate Student
Hang Su
Midhun Thomas, Ph.D.
Post Doc Research Associate
Midhun Thomas Tian Zhou
Graduate Student
Tian Zhou

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