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Eleven data generation projects are currently funded by the SCORCH initiative:
UCSD SCORCH (Cheng, 5UM1DA051411-03)
This project will perform single nucleus RNA sequencing (snRNA-seq) on three brain regions with the possibility of identifying gene targets that exhibit region and cell type specific selectivity of opioid use disorder in the context of HIV/HIV associated neurocognitive impairment.
This project will perform snRNA-seq, single-nucleus ATAC-seq (scATAC-seq), and spatial transcriptomics on 20 brains from four donor groups: controls, HIV (HIV+), HIV with OUD (HIV+OUD+), and OUD without HIV (OUD+). Three regions which represent disease-relevant areas for OUD and HIV, will be assayed: prefrontal cortex, ventral striatum and insular cortex.
This project will generate a single-cell transcriptome and regulome atlas of gene regulatory networks in the human brain during neuroimmunologic perturbations by methamphetamine and HIV infection.
Mount Sinai SCORCH (Akbarian, U01DA053600-01)
This project will engage in mapping cell specific transcriptomes in monoaminergic circuitry associated with prospectively monitored neurological status in the years before death and exposure to drug of abuse. It will also explore whether or not opiate and cocaine exposures affect HIV neurogenomic activity.
Mount Sinai SCORCH (Kenny, U01DA053629-01)
This project will leverage state-of-the-art single cell and single nuclei RNA sequencing combined with molecular, cellular and behavioral approaches to define cell type-specific interactions between HIV and opioids in the brains of EcoHIV-infected mice.
UNMC SCORCH (1U01DA053624-01)
This project 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.
BROAD SCORCH (1U01DA053631-01)
This project will dissect the transcriptional and epigenetic changes associated with SUD and persistent HIV infection at single-cell resolution across seven human brain regions, and integrate the resulting datasets to predict driver genes.
UCSD SCORCH (Rana, 1U01DA053630-01)
This project puts forward an unprecedented concept and experimental system to identify single cell determinants of the brain relevant to persistent HIV infection and opioid use disorder as well as potential opportunities to illuminate how genetic variation affects gene expression.
- Tariq Rana, PhD
University of California San Diego
Weill Cornell SCORCH (1U01DA053625-01)
This projects seeks to generate topographical data sets and evidence at single cell resolution across the hippocampus and prefrontal cortex (PFC), two brain regions known for predilection for HIV persistence and OUD in non-human primate (NHP) and in post-mortem human brain. These data will provide an unprecedented cellular landscape of multiple modalities that can be harnessed to develop strategies to limit viral persistence and restore and retain optimal brain health in people living with HIV.
Scripps Research SCORCH (1U01DA056004-01)
The abuse of stimulants such as methamphetamine (METH) exacerbates the deleterious effects of HIV infection. This project will carry out single nucleus RNA-Seq with the goal of identifying cell types and cell states that are pivotal in the effects of HIV and chronic methamphetamine (METH) self-administration on key brain regions relevant to the effects of persistent HIV infection and METH use disorder in HIV transgenic (Tg) rats, which harbor a non-replicating HIV-1 transgene and express chronic low-levels of multiple HIV-1 proteins.
- Pietro Sanna, MD
Allen Institute SCORCH (1U01DA056003-01)
This project will leverage state-of-the-art single-nuclei RNA sequencing (snRNA-seq) coupled to single-nuclei epigenetics (snATAC-seq) to define the transcriptional and epigenetic landscape of neuronal and nonneuronal cells in addiction-relevant brain cells of HIV-infected mice that compulsively self-administer cocaine. In this manner cell types and brain sites in which HIV and cocaine interact to exacerbate the negative impact of HIV infection on the brain and contribute to the persistence of cocaine use disorder in infected individuals will be identified.