A K02 independent Scientist Award will enable the candidate to obtain maximally 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 grants R01 DA018633, """"""""Mechanisms of opiate drug-HIV-induced neurodegeneration"""""""" and R01 DA033200 """"""""Regulation of HIV and opiate-directed synaptodendritic injury/death in striatum"""""""", and is a multi-Pl on R01 DA034231 """"""""Glial origins of HIV and opiate-driven synaptodendritic injury"""""""", and is a co-l on other grants 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., whole-cell patch-clamp electrophysiology) to assess the trigger events underlying opiate and HIV interactive synaptodendritic injury) and better models of substance abuse (self-administration). (2) To merge basic and clinical approaches through translational research using engineered HIV proviral vectors as a novel source non-infectious HIV/""""""""virotoxins"""""""" for studying electrophysiological effects in bystander neurons and to adopt CRISPRs (clustered regularly interspaced short palindromic repeats), a genome editing strategy, with the goal of completely eliminating or adding receptor genes (e.g., OPRM1). The candidate will continue to mentor students/early career scientists (including under-represented individuals and with 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 the candidate also discovered that opioids intrinsically promote the neurodegenerative effects of HIV in the brain. The candidate respectfully requests this award to devote significant time to pursue cutting-edge research into the fundamental mechanisms underlying opioid drug abuse-HIV interactions to identify 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 #
2K02DA027374-06
Application #
8790219
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Sorensen, Roger
Project Start
2009-07-01
Project End
2019-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
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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

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