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Uncovering HIV/opioid effects in the brain at the single cell level: transcription, chromatin accessibility, and reservoir analysis in the SIV/cART/morphine/rhesus monkey model

Award Number: U01DA053624
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Uncovering HIV/opioid effects in the brain at the single cell level: transcription, chromatin accessibility, and reservoir analysis in the SIV/cART/morphine/rhesus monkey model - Project Summary A comprehensive interdisciplinary approach proposed to support the Single Cell Opioid Responses in the Context of HIV (SCORCH) Program Expansion: CNS Data Generation for Chronic Opioid, Methamphetamine, and/or Cocaine Exposures RFA from the National Institute on Drug Abuse (NIDA). We will perform studies on the interplay of HIV pathogenesis and opioid abuse in the gold-standard SIV/nonhuman primate system, using single-cell RNA sequencing (scRNAseq) to assess individual cellular transcriptomes. This will give us obtain unparalleled insight into the viral and drug-induced effects on diverse cell types in brain in regions critical for HIV infection and opioid abuse. In addition, we will also focus on primary targets of HIV and drivers of neuropathogenesis, microglia and brain macrophages, using scRNAseq as well as single-cell Assay for Transposase-Accessible Chromatin sequencing (scATACseq) to gain insight into the epigenetic regulation of gene expression at the single cell level. These will be combined with state-of-the-art sensitive assays for virus in the brain. We will ensure our data adhere to the FAIR (Findable, Accessible, Interoperable, and Reusable) standards, and will work closely with other members of the SCORCH program to share and disseminate data to yield maximal advancement to the field. Our experiments are carefully designed to address the role of virus, drugs, and their interactions, as well as include the clinically relevant scenarios of those taking antiretrovirals to suppress virus, and those who do not. Our rigor and reproducibility are facilitated by our detailed power analysis with proper sample sizes, as well as our experimental design to match the standards of blocking, replication and randomization. The results from these studies will provide novel insights into the CNS effects of HIV and drug abuse.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $929,071 )
2025	2025	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Drug Use and Addiction Research Programs	000	5	7/18/2025	NON-COMPETING CONTINUATION	$929,071
														Subtotal = $929,071

Issue Date FY: 2024 ( Subtotal = $1,579,167 )
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Drug Use and Addiction Research Programs	001	4	6/27/2024	NON-COMPETING CONTINUATION	$1,579,167
2024	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Drug Use and Addiction Research Programs	000	3	2/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,579,167

Issue Date FY: 2023 ( Subtotal = $2,099,091 )
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Drug Use and Addiction Research Programs	000	3	6/29/2023	NON-COMPETING CONTINUATION	$2,099,091
														Subtotal = $2,099,091

Issue Date FY: 2022 ( Subtotal = $2,219,107 )
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Drug Use and Addiction Research Programs	000	2	7/14/2022	NON-COMPETING CONTINUATION	$2,093,258
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Drug Use and Addiction Research Programs	001	2	9/6/2022	SUPPLEMENT FOR EXPANSION	$125,849
														Subtotal = $2,219,107

Issue Date FY: 2021 ( Subtotal = $1,417,351 )
2021	2021	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Drug Use and Addiction Research Programs	000	1	8/13/2021	NEW	$1,417,351
														Subtotal = $1,417,351

Grand Total All Awards = $8,243,787

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Uncovering HIV/opioid effects in the brain at the single cell level: transcription, chromatin accessibility, and reservoir analysis in the SIV/cART/morphine/rhesus monkey model

Award Number: U01DA053624

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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