Fox Lab

Dr. Fox's Bio

Howard Fox, MD, Ph.D.

Collaborators
Shilpa Buch, PhD, Department of Pharmacology and Experimental Neuroscience, UNMC
Siddappa Byrareddy, PhD, Department of Pharmacology and Experimental Neuroscience, UNMC
Pawel Ciborowski, PhD, Department of Pharmacology and Experimental Neuroscience, UNMC
Peter Gaskill, PhD, Department of Pharmacology & Physiology, Drexel University, Philadelphia
Howard E. Gendelman, MD, Department of Pharmacology and Experimental Neuroscience, UNMC
Kelly Stauch, PhD, Department of Neurological Sciences, UNMC
Gary Siuzdak, PhD, The Scripps Research Institutes, San Diego
Cecilia Marcondes, PhD, San Diego Biomedical Research Institute 
Olga Taraschenko, MD, PhD, Department of Neurological Sciences, UNMC
Sowmya Yelamanchili, PhD, Department of Anesthesiology, UNMC

Funding

Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Centerr
MPI: Fox, H and Buch, S
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, H
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; Co-Director: 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
The major goals of this project are to develop a pharmacologic-based strategy using combinations of existing and new antiretroviral (ARV) drugs to design ARV regimens with enhanced penetration into lymphoid tissues to more fully suppress HIV production in that compartment and avert the long-term consequences of persistent viral production.

NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence
PI: Gendelman, H.E.; Animal 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.
 
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.

Macrophage, Meth, HIV and Histones: An Interplay
NIH/NIDA 5R01 DA043258
PI: Ciborowski P; Co-I: Fox H
The complexity of HIV infection is further complicated and intensified by use of drugs of abuse. Methamphetamine (Meth) is a drug with increasing popularity among the drug-abusing population and used by those with, or at risk for HIV. Treatment of these individuals is a very complex process and despite substantive research efforts, the broad picture of molecular mechanisms underlying functions of macrophages (MP) in the complex environment of HIV-1 infection and/or Meth use is far from being understood. We expect that targeted profiling, computational biology, and bioinformatic analyses will uncover new and unreported mechanisms of MP regulation 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.

Parkin as a Protective Strategy Against Mitochondrial DNA Stress
Michael J. Fox Foundation
PI: Fox H
This study examines the hypothesis that enhancing Parkin function mediates increased quality control in conditions of mitochondrial stress.

Mechanisms of Synaptic Energetic Failure Due to Pink1/Parkin Deficiency
Michael J. Fox Foundation
PI: Stauch K; Co-I: Fox H
The application proposes studies that will test the hypothesis that combined Pink1/Parkin deficiency leads to a reproducible rat model of Parkinson’s disease due to the accumulation of damaged/dysfunctional mitochondria at striatal synapses resulting in energetic failure and deficient neurotransmitter release. Determining mechanisms of region-specificity of mitochondrial dysfunction and selective vulnerability of striatal nerve terminals in this novel rat model will significantly advance the understanding of neurodegeneration linked to Pink1/Parkin mutations and potentially idiopathic PD.

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

Raj Dave, PhD
Instructor

Rajnish Dave, Ph.D.

Katy Emanuel
Research Technologist II

Katy Emanuel

Anna Fangmeier
Research Technologist

Anna Fangmeier

Trey Farmer
Post-Doc Research Associate

co-mentored with Kelly Stauch

Trey Farmer, Post-doc Research Associate 

Ashley Hanson
NNTC Data Coordinator II

Ashley Hanson

Benjamin Lamberty
Research Technologist II

Ben Lamberty

Eliezer Lichter
Graduate Research Assistant

co-mentored with Kelly Stauch

Eliezer Lichter
Brenda Morsey
Research Coordinator
402-559-5322
Brenda Morsey
Steven Totusek
Data Coordinator II
Steven Totusek

Andrew Trease, PhD
Post Doc Research Associate

 Andrew Trease, PhD