Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Identification and interrogation of glial gene signatures in volitional opioid seeking

Award Number: DP1DA066476
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

Group Awards By:

View Award Description

Identification and interrogation of glial gene signatures in volitional opioid seeking - Project Summary Drug addiction remains a pervasive public health crisis, affecting millions of individuals worldwide. Despite the enormous societal cost and continued increase in opioid-related overdoses, treatment options are limited. This is due in part to our incomplete understanding of which molecular adaptations initiated by opioid use are necessary for the transition to the addicted state. An inherent challenge in identifying and isolating the key transcriptional changes driving this process is the diverse cellular composition in mesolimbic reward regions, including glial populations like astrocytes, microglia, and oligodendrocytes. More recently, converging lines of research demonstrate that these glial populations play a central role in the transition to addiction. However, our ability to harness the therapeutic potential of glial-specific transcriptional and epigenetic manipulations in the context of addiction has been limited by a lack of detailed insight into which specific gene signatures are initiated during persistent drug taking, and the inability to selectively target these alterations in real time to interrogate their role in cellular and behavioral function. The majority of transcriptomic and chromatin profiling in the context of opioid misuse has relied on either bulk tissue homogenates or neuron-centric sequencing experiments. While informative, such approaches do not allow for in-depth examination of glial-specific molecular signatures induced by drugs of abuse. Another challenge in understanding the complex nature of drug-induced alternations in glia is the lack of available tools for selective modulation of gene targets in these populations. Traditional CRISPR gene and epigenetic editing approaches have focused primarily on cell-agnostic or neuronal modulation of individual gene targets. To overcome these hurdles, this proposal will utilize single-nuclei RNA-sequencing (snRNA-seq) and the Assay for Transposase-Accessible Chromatin (snATAC-seq) to define glial-specific gene signatures of contingent drug use in the mesolimbic reward circuitry of male and female rats. In addition to revealing novel and potentially sex-specific therapeutic candidates, this information will be utilized to engineer new CRISPR/dCas9-based epigenetic editing tools, which will allow for manipulation of drug-responsive genes in discrete glial populations. This approach will enable selective modification of individual or multiple gene targets simultaneously, effectively allowing us to test the requirement of complex glial gene programs in a volitional model of drug use. Collectively, the proposed experiments will be the first to define the exact nature and scope of glial-specific gene signatures following sustained drug experience, and to mechanistically link the requirement of these gene programs in reward neurocircuitry during drug self-administration.


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: 2026 ( Subtotal = $468,000 )
2026	2026	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Drug Use and Addiction Research Programs	000	1	9/3/2026	NEW	$468,000
														Subtotal = $468,000

Grand Total All Awards = $468,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Identification and interrogation of glial gene signatures in volitional opioid seeking

Award Number: DP1DA066476

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer