SCORCH (Single Cell Opioid Responses in the Context of HIV) Program

Purpose

Illustration of the brain showing various regions

The purpose of NIDA’s SCORCH (Single Cell Opioid Responses in the Context of HIV) Program is to support generation and sharing of single nucleus RNA-sequencing and epigenomic data sets for brain regions relevant to persistent HIV infection and opioid use disorder (OUD). 

Funding

Since initial funding of two SCORCH data generation projects through RFA-DA-19-037, SCORCH data generation has been expanded beyond OUD to include cocaine or methamphetamine use disorder through RFA-DA-21-019 and NOT-DA-20-063.

In parallel through RFA-DA-19-038, a SCORCH data coordination, analysis, and scientific outreach center was established to standardize and share single cell molecular HIV/SUD data generated by this program with the scientific community by ensuring that the data is FAIR (Findable, Accessible, Interoperable, and Reusable).

Significance 

If fully successful, the SCORCH project will

  1. Establish cell type-specific gene expression differences in particular brain regions, potentially enabling precision genetic or pharmacological manipulation
  2. Reveal the molecular effects of HIV infection/treatment in the CNS, providing potential targets for addressing HIV persistence and/or HIV neurobiological sequelae
  3. Uncover cell type-specific gene expression and epigenomic changes resulting from chronic opioid, cocaine, and/or methamphetamine exposure providing potential novel therapeutic targets to treat addiction
  4. Identify potential synergistic effects of chronic addictive substance exposure and HIV infection in the CNS

SCORCH Scientific Overview

Seven data generation projects currently perform single nucleus transcriptomic or epigenomic assays on HIV/SIV/EcoHIV and/or OUD-relevant brains from human, primate, or mouse.  Some brain regions currently targeted include prefrontal cortex, dorsal and ventral striatum, nucleus accumbens, habenula, and hippocampus.  One project is assaying substantia nigra, locus coeruleus, and dorsal raphe from human opioid/cocaine users with and without HIV.  Another project is investigating the effects of HIV with and without methamphetamine use in human prefrontal cortex, ventral striatum, and amygdala.  For more detailed information, please see the SCORCH program website or individual abstracts of the funded projects below.

Funded SCORCH Projects:

  • NeMO Archive: SCORCH Support, Coordination, and Outreach (UM1DA052244), University of Maryland Baltimore
  • Single Cell Transcriptomics of the Opioid Use Disorder and HIV Syndemic in the Human Brain, (UM1DA051411-01), JCVI SCORCH 
  • The Y-SCORCH Data Generation Center at Yale for Single-Cell Opioid Responses in the Context of HIV (UM1DA051410-01), Yale University
  • Single nuclei transcriptome profiling in addiction circuitry of the HIV+ brain (U01DA053600-01), Mount Sinai SCORCH 
  • M-SCORCH: Methamphetamine use disorder data generation center for Single Cell Opioid Responses in the Context of HIV (U01DA053628-01), M-SCORCH 
  • Single cell brain transcriptome changes during chronic HIV infection and opiate use in conventional mice (U01DA053629-01), Mount Sinai SCORCH 
  • 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 (1U01DA053624-01), UNMC SCORCH 
  • Single Cell Transcriptomic and Epigenomic Dissection of Opioid and Cocaine Responses in HIV (1U01DA053631-01), MIT/BROAD SCORCH 
  • Revealing the single cell determinants of brain relevant to persistent HIV infection and opioid use disorder(1U01DA053630-01), UCSD SCORCH
  • Integrative Single Cell isoform and chromatin accessibility Mapping of Chronic Opioid Exposure in Cognitive Brain Areas in HIV (1U01DA053625-01), Weill Cornell SCORCH 
  • Single nucleus gene expression in moderate and compulsive drug self-administration in a rodent model of HIV (1U01DA056004-01), Scripps Research Institute
  • Single cell transcriptomic and epigenomic changes during chronic HIV infection and cocaine self-administration (1U01DA056003-01), Allen Institute
  • Single Cell Transcriptomics of the Cocaine Use Disorder in the Context of HIV (1U01DA056006), UCSD Cheng

Questions

Several DNB staff work on SCORCH including John Satterlee Ph.D. and Susan Wright Ph.D. as program officers with Anne Tsai Ph.D. and Holly Moore Ph.D. as project scientists.  If you have questions about SCORCH, please contact John Satterlee satterleej@nida.nih.gov