Howard Fox's laboratory

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Howard E. Gendelman, M.D., Department of Pharmacology and Experimental Neuroscience, UNMC
Pawel Ciborowski, Ph.D., Department of Pharmacology and Experimental Neuroscience, UNMC 
Shilpa Buch, Ph.D., Department of Pharmacology and Experimental Neuroscience, UNMC 
Gary Siuzdak, Ph.D., The Scripps Research Institutes, San Diego
Cecilia Marcondes, Ph.D., The Scripps Research Institutes, San Diego 
Igor Grant, M.D., F.R.C.P.(C), University of California, San Diego 
Scott Letendre, M.D., University of California, San Diego 
Ronald Ellis, M.D., Ph.D., University of California, San Diego
Olha Taraschenko, M.D., Ph.D., Department of Neurological Sciences, UNMC


Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Centerr
MPI: Fox, Howard and Buch, Shilpa
NIH/NIMH  5 P30 MH062261
The goal of this project is to provide administrative and core support for scientists investigating NeuroAIDS.

NNTC Data Coordinating Center
PI: Fox, Howard
NIH/NIMH U24 MH100925
The NNTC has served as a valuable resource to the NeuroAIDS research community since 1998. Its continuation is critical given the need for quality CNS tissues and related antemortem clinical data. For this grant I serve as the leader of the Steering Committee which determines direction and policy to serve investigators using these resources (a consortium of 4 brain banks) to examine emerging research topics in the NeuroAIDS field such as: a) eradication of HIV from persistent CNS reservoirs; b) pathogenic mechanisms of HIV-associated neurocognitive disorders (HAND) in setting of long term HAART; and c) HIV and aging. Furthermore we are responsible for all the data obtained clinically on the subjects and experimentally on the specimens, and are the interface between requesting scientists and the brain bank sites.

Great Plains IDeA-CTR
NIH/NIGMS 1U54GM115458-01
PI: Rizzo, M; PI Pilot Program: Fox, H.
This is a grant to support clinical and translational research at UNMC and partner institutions in Nebraska, South Dakota and North Dakota. Dr. Fox directs the Pilot Project program.

Role of extracellular vesicles in methamphetamine mediated neurotoxicity
NIH/NIDA 5R01DA042379
PI: Yelamanchili, S; Co-I: Fox, H
HIV-1 infection is an ongoing pandemic, and although treatment is available the cognitive disorders continue to affect infected individuals. We have found a neurotoxic molecule, microRNA miR-21 to be significantly upregulated in the SIV/HIV-1 infected brain. Our studies are designed to uncover the mechanisms of its damaging effects that could subsequently lead to preventative and therapeutic measures.

The Lymphoid Tissue Pharmacology of Antiretroviral Drugs
PI: Fletcher; C; Co-I-: Fox, H.
NIH/NIA: R01AI124965

NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence
PI: Gendelman, H.E.; Core PI: Fox, H
NIH/NIDA 5P01DA028555
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.

The brain as a SIV reservoir under suppressive cART potentiation by drugs of abuse
NIH/NIDA: 1 R01 DA043164-01 
MPI: Fox H/Buch S/Byrareddy S
Using the SIV/macaque system, we will determine whether the brain is a viral reservoir in the setting of effective treatment, and will measure the effect of two commonly used drugs of abuse, morphine and methamphetamine, on the brain reservoir. Mechanisms by which drug abuse affect the viral reservoir will be examined, thus leading to strategies to target this reservoir to effect a cure in those with and without substance abuse.

Mechanisms of dopamine mediated increase in HIV infection of macrophages
PI: Fox, H
Drexel University
This is part of an NIH grant that supports the investigation of the effect of dopamine on HIV infection by a researcher at Drexel. Our subcontract supports in vivo studies in nonhuman primates examining the effect of agents that increase dopamine on acute infection of the brain by SIV.
Effect of Elevated Parkin on Brain Mitochondrial Bioenergetics and Proteome Dynamics
PI: Fox, H
Michael J. Fox Foundation
This grant supports the characterization of synaptic mitochondria in mice expressing either a “disinhibited” mutant Parkin, or multiple copies of human Parkin, to test the potential protective effect.
Opiate induced SIV-Neuropathogenesis:  Role of miRNA-29b in the Periphery-CNS Crosstalk
NIH/NIDA  5 R01 DA035203-02 
PI: Buch, S.; Co-I: Fox, H.
The goal of this project is to use an established opiate dependent simian model of neuroAIDS combined with microRNA profiling to understand how periphery-CNS cross talk leads to disease progression.
HIV-1 mediated synaptodendritic injury and microglial activation: Role of extracellular vesicle miRNAs
NIH/NIMH 1R01MH112848-01
PI: Buch, S; Co-Fox
The application proposes studies that will test the hypothesis that loss of dendritic spines and functional synapses (synaptodendritic) and the associated cognitive decline mediated by HIV proteins can be reversed by platelet-derived growth factor (PDGF)- CC, through activation of intracellular signaling pathways.
HIV Tat & cocaine-mediated alterations in microglial migration & activation involve epigenetic regulation or miRNAs
NIH/NIDA 5R01DA043138
PI: Buch S; Co-I: Fox, H
The goal of this proposal is to explore how cocaine and HIV Tat modulate increased microglial activation and migration respectively, via DNA methylation of microRNA 124 promoter, leading in turn, to increased TLR4 signaling and also via up regulation of miR-9 leading to enhanced microglial migration.
HIV Tat and Morphine Induce Microglial Migration and Activation via Release of miR-9 and 138
NIH/NIDA 1R01 DA040397
MPI: Fox H/Buch S
This grant aims to explore how viral protein such as Tat induces miRNA-9 in exosomes from the astrocytes leading to increased migration of microglia. We also propose to understand how morphine exposure of astrocytes can upregulate miRNA-138 in exosomes, which leads to increased microglial activation. Together HIV proteins and opiates co-operate to inflict increased glial migration and activation, thereby contributing to disease severity.

Techniques used in the laboratory


Mohannad Almikhlafi
Graduate Research Assistant

Mohannad Almikhlafi
Jenny Brady
Administrative Assistant
Jenny Brady
Shannon Callen
Research Coordinator
Shannon Callen

Allison Dye
Data Coordinator I


Anna Fangmeier
Research Technologist

Anna Fangmeier

Abigail Heithoff
Data Coordinator II

Abigail Heithoff

Benjamin Lamberty
Research Technologist II

Ben Lamberty
Brenda Morsey
Research Coordinator
Brenda Morsey
Kelly Stauch, Ph.D.
Kelly Stauch
Steven Totusek
Data Coordinator II
Steven Totusek
Niming Wu
Graduate Research Assistant
Niming Wu

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