Howard Fox's laboratory

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Funding
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Collaborators

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


Funding

Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center
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.

Elucidating the role of exosomal miR-21 in SIV/HIV neurological dysfunction
NIH/NIMH R21 MH106422-02
MPI: Yelamanchili, S; 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: R01AI12496

NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence
PI: Gendelman, H.E.; Core PI: Fox, H
NIH/NIDA 5PO1DA028555
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.

Macrophage, Meth, HIV and Histones:  An Interplay
NIH/NIDA 1 R01 DA043258-01 
MPI: Ciborowski P/ Fox H
We will perform high-throughput omics (proteomics, transcriptomics, genomics) combined with targeted profiling, computational biology, and bioinformatic analyses will uncover new and unreported mechanisms of the interaction of methamphetamine and HIV in macrophages, and will model functional networks that can be validated by focused and targeted experiments as they exist in ex vivo material from non-human primates. Better understanding of the epigenetic regulation of MP will enable us to define weak points of the major target cell under insult of viral infection and Meth.

PI: Fox, H
NIH/NIMH 5R21MH106422
The project examines the role of brain exosomes in the neurological damage due to HIV infection of the brain. Specifically we will examine the role of miR-21 in exosomes from brains of those with neuroAIDS, and its role in inducing neuronal damage.
 
Effect of Elevated Parkin on Brain Mitochondrial Bioenergetics and Proteome Dynamics
PI: Fox, H
Michael J. Fox Foundation
 
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


Personnel

Mohannad Almikhlafi
Graduate Research Assistant

Mohannad Almikhlafi
Jenny Brady
Administrative Assistant
402-559-4820
Jenny Brady
Shannon Callen
Research Coordinator
Shannon Callen

Allison Dye
Data Coordinator I

Allison_Dye

Anna Fangmeier
Research Technologist

Anna Fangmeier

Abigail Heithoff
Data Coordinator II

Abigail Heithoff

Benjamin Lamberty
Research Technologist II

ben lamberty

Brenda Morsey
Research Coordinator
402-559-5322

Brenda Morsey

Rebecca Sujatha Sampathkumar
Research Assistant
Rebecca_Sujatha_Sampathkumar
Kelly Stauch, Ph.D.
Instructor

kelly stauch

Steven Totusek
Data Coordinator II
Steven Totusek
Niming Wu
Graduate Research Assistant
Niming Wu

Dr. Fox's Home Page
Dr. Fox's Biographical Information
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