A K02 independent Scientist Award will enable the candidate to obtain maximum protected time at Virginia Commonwealth University (VCU) to pursue NIDA funded research on substance abuse-HIV-1 comorbidity, acquire advanced cross-disciplinary expertise, and to mentor student and faculty scientists in this area. Drug abuse and HIV-1 are interlinked epidemics with horrific consequences. To address this problem, the candidate directs grant P01 DAI 9398, "Opiate drug abuse and CNS vulnerability to HIV", is PI on grant ROI DA18633, "Mechanisms of opiate drug-HIV:lnduced neurodegeneration", is a co-l on a R01 DA024461 "Glial progenitors as targets of HIV/opiate interactions", is a co-l on a pending NIDA ROS grant to study opioid drug-hepatitis C virus (HCV) interactive pathology, and consultant on numerous other projects. The applicant has published seminal studies demonstrating: that opioids can directly affect CNS maturation;the cellular basis of opioid receptor and function in astrocytes and oligodendrocytes;and that opioids intrinsically exacerbate the pathogenesis of neuroAIDS-identifying both intra- and intercellular pathologic mechanisms in neurons and multiple glial types. The applicant has established worldwide collaborations that continue to optimize approaches to opioid abuse-HIV-1 comorbidity, has mentored highly successful pre- and postdoctoral, and basic and clinical faculty;including training in the responsible conduct of research (RCR), has co-directed a NIDA training grant, and organized local and international conferences promoting substance abuse research. A K02 award will enable the candidate to: (1) pursue the goals of current grants, while developing cutting-edge approaches to substance abuse (e.g., self-administration paradigms), HlV-1 (humanized SCID mouse model), and molecular neurovirology;(2) to merge basic and clinical approaches through translational research with the VCU HIV/AIDS Center and joint VCU/Johns Hopkins Univ. NIDA CTN;while continuing to mentor students/early career scientists (including under-represented individuals and an emphasis on RCR). He was recruited to VCU by the Dept. of Pharmacology and Toxicology to pursue these goals and receives tremendous support for this endeavor.

Public Health Relevance

Opioid (heroin) abuse and HIV/AIDS are interrelated epidemics. Not only does drug abuse spread HIV, but also the candidate discovered that opioids intrinsically promote the neurodegenerative effects of HIV. The candidate respectfully requests this award to devote more time to pursue research into the mechanisms underlying opioid drug abuse-HIV interactions to indentify new therapies for opioid abuse and neuroAIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA027374-04
Application #
8284484
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Sorensen, Roger
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$129,082
Indirect Cost
$9,562
Name
Virginia Commonwealth University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Fitting, Sylvia; Stevens, David L; Khan, Fayez A et al. (2016) Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice. J Pharmacol Exp Ther 356:96-105
Guedia, Joy; Brun, Paola; Bhave, Sukhada et al. (2016) HIV-1 Tat exacerbates lipopolysaccharide-induced cytokine release via TLR4 signaling in the enteric nervous system. Sci Rep 6:31203
Marks, William D; Paris, Jason J; Schier, Christina J et al. (2016) HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations. J Neurovirol 22:747-762
Hahn, Yun K; Paris, Jason J; Lichtman, Aron H et al. (2016) Central HIV-1 Tat exposure elevates anxiety and fear conditioned responses of male mice concurrent with altered mu-opioid receptor-mediated G-protein activation and β-arrestin 2 activity in the forebrain. Neurobiol Dis 92:124-36
Paris, Jason J; Zou, ShiPing; Hahn, Yun K et al. (2016) 5α-reduced progestogens ameliorate mood-related behavioral pathology, neurotoxicity, and microgliosis associated with exposure to HIV-1 Tat. Brain Behav Immun 55:202-14
Fitting, S; Ngwainmbi, J; Kang, M et al. (2015) Sensitization of enteric neurons to morphine by HIV-1 Tat protein. Neurogastroenterol Motil 27:468-80
Masvekar, Ruturaj R; El-Hage, Nazira; Hauser, Kurt F et al. (2015) GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity. Mol Cell Neurosci 65:11-20
Bhardwaj, Reetika; Yester, Jessie W; Singh, Sandeep K et al. (2015) RelB/p50 complexes regulate cytokine-induced YKL-40 expression. J Immunol 194:2862-70
Ellis, Kelstan; Marlin, Jerry W; Taylor, Tracey A H et al. (2015) The effects of human immunodeficiency virus infection on the expression of the drug efflux proteins P-glycoprotein and breast cancer resistance protein in a human intestine model. J Pharm Pharmacol 67:178-88
Sahu, Geetaram; Farley, Kalamo; El-Hage, Nazira et al. (2015) Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR. Virology 483:185-202

Showing the most recent 10 out of 46 publications