Subhash Pandey
University of Illinois Chicago, IL·Neuroscience
People with alcohol use disorder (AUD) who try to stop drinking often face withdrawal symptoms such as anxiety. These symptoms are a major reason people relapse.
- Fields
Neuroscience
Pharmacology
Genetics
- Topics
alcohol use disorder
alcohol withdrawal
anxiety
- Grants
- 3 known grants, through May 2030
What they work on
- Test whether EZH2, an enzyme that adds methyl tags to histones, controls synaptic genes, electrical activity, synapse structure and anxiety-like behavior in the central amygdala of male and female rats during alcohol withdrawal, and examine these genes in postmortem human AUD amygdala.
- Map cell type-specific changes in gene activity and DNA openness in the rat central amygdala during alcohol withdrawal using single-cell snRNA-seq and snATAC-seq, and confirm key genes with spatial transcriptomics.
- Test whether cell type-specific epigenetic editing with dCas9-P300 or dCas9-KRAB delivered by lentivirus normalizes gene expression, synapse structure seen by 3D electron microscopy, neurotransmission and anxiety-like behavior during withdrawal.
- Link cell type-specific epigenetic and gene-activity changes in four brain regions to withdrawal behaviors such as anxiety, depression, pain and cognitive deficits, using single-cell genomics and CRISPR-dCas9 or shRNA manipulation across the CARE center.
- Identify open and closed chromatin regions in the adult rat amygdala after adolescent intermittent ethanol exposure using ATAC-seq, combined with RNA-seq, and test the role of these marks with CRISPR-dCas9 epigenetic editing.
- Test whether the G9a inhibitor UNC0642 reverses adolescent alcohol-induced epigenetic, gene and dendritic spine changes in the amygdala and reduces adult anxiety-like and drinking behaviors in rats, and compare findings with human early-onset AUD brain tissue.
More about the research
Heavy drinking changes the brain partly through epigenetics: chemical tags on DNA and on histones, the proteins DNA wraps around, that switch genes on or off without changing the genetic code. The projects here ask how these tags change in specific brain cell types after chronic or adolescent alcohol exposure, how those changes alter brain circuits and behavior, and whether reversing them can relieve symptoms. Much of the work centers on the amygdala, a brain region that handles fear and anxiety, using rat models and postmortem human brain tissue.
Why it matters
Alcohol use disorder is a major public health problem, and withdrawal symptoms such as anxiety drive relapse. Identifying epigenetic changes in specific brain cell types could reveal new drug targets for treating withdrawal symptoms and preventing AUD. The adolescent studies could help explain why teenage binge drinking raises the risk of anxiety and AUD in adulthood, and may point to therapies for these later problems.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Claes Wahlestedt
University of Miami, FL·Neuroscience
Profile the silencing histone mark H3K27me3 in amygdala neurons and non-neuronal cells of rats that drink alcohol compulsively despite foot-shock, using CUT&RUN mapping, and link differences to gene expression with RNA sequencing.
Samuel Centanni
Wake Forest University, NC·Neuroscience
Test whether stress-driven activity in the insula-BNST pathway predicts later binge and aversion-resistant ethanol drinking, following mouse models of stress and binge drinking over time.
Erbo Dong
Ohio State University, OH·Neuroscience
Determine whether PP1a, an enzyme that promotes HDAC4 build-up in the nucleus, drives the ethanol preference, tolerance and anxiety-like behavior seen in adult mouse offspring of prenatally stressed mothers.
The school
University of Illinois Chicago: 42 labs on PI Pages, $532M a year on research, 359 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.