U01DA053600

Single Nuclei Transcriptome Profiling in Addiction Circuitry of the HIV+ Brain - HIV-Associated Neurocognitive Disorders (HAND) persist in the era of Combination Antiretroviral Therapy (CART).

HIV latency, and cell-specific expression of HIV transcript in the human central nervous system (CNS) remains incompletely understood, despite the continued high prevalence of HIV-associated neurologic disease and increasing recognition of CNS viral escape in people stably suppressed with CART. One of the major issues regarding CNS HIV in need of study is HIV integration. In other words, whether CNS HIV integration has a biologically significant impact, contributing to pathogenesis.

Issues of CNS functional deficit are further complicated by the co-occurring epidemic of opiate and other substance use disorders (SUD) in people living with HIV/AIDS (PLWHA), as SUD also have a profound impact on CNS function, and potentially on HIV latency. Nowhere in the CNS is this more evident than in the neuroanatomic overlap of HIV and SUD in striatonigral dopaminergic circuitry and frontostriatal projections, sites of predilection for functional and neurobiologic disease as well as for an increased burden of HIV infection.

Accordingly, directly utilizing brain tissues in these regions, from neurologically well-characterized HIV-infected individuals with and without SUD, the goal of this application will be:
(I) to replicate for the brain some of the emerging genomic mechanisms recently discovered in peripheral cells, linking HIV host genome integration and virus latency to nuclear topography and open chromatin;
(II) to explore whether HIV signatures in transcriptomes and epigenomes in dopaminergic circuitry including frontal and striatal targets are associated with prospectively monitored neurological status in the years before death and exposure to drug of abuse;
(III) explore HIV expression in potential reservoir cells of the brain, including microglia.

The innovative experiments proposed here are expected to offer novel insights into transcriptomic landscapes in specific brain cells and explore potential links between neurogenomic status of the infected brain and neurological and cognitive symptoms and substance abuse. While recognizing the high-risk aspects, these analyses will nevertheless have predictable, high-gain benefits in understanding the complex neurobiology underlying HIV-associated CNS disease in PLWHA and SUD.

Icahn School Of Medicine At Mount Sinai

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

New York, New York 100296504 United States

Single Zip Code

Single Cell Opioid Responses in the Context of HIV (SCORCH) Program Expansion: CNS Data Generation for Chronic Opioid, Methamphetamine, and/or Cocaine Exposures (U01 Clinical Trial Not Allowed) (RFA-DA-21-019)

Amendment Since initial award the total obligations have increased 441% from $796,024 to $4,310,228.