New York University School of Medicine has received a USD 1.69 million NIH R56 award to investigate the role of long non-coding RNAs in stress susceptibility and resilience, signaling growing NIMH interest in epigenetic contributors to psychiatric vulnerability.
The grant, administered through the National Institute of Mental Health, runs through June 2028 and is led by principal investigator Orna Issler. The R56 mechanism typically supports high-priority research bridging preliminary findings toward larger funding applications, suggesting NIMH views lncRNA biology in stress response as a credible translational target.
The central scientific question is why chronic stress precipitates psychiatric disorders in some individuals while others remain resilient. Long non-coding RNAs — a class of epigenetic regulators that do not encode proteins but modulate gene expression — are expressed abundantly in the brain and have emerged from genomic and transcriptomic analyses of depression as potentially relevant to this variability. The project combines bioinformatic integration of genome-wide association study data for depression with experimental validation in a mouse chronic stress model, focusing on the prefrontal cortex. A specific candidate, LINC02977, identified through multi-omics analysis, will be examined in animals of both sexes — an inclusion that reflects broader NIH mandates to account for sex as a biological variable in preclinical research.
The work is positioned at an early but mechanistically important stage: characterizing which lncRNAs are functionally relevant to stress resilience, rather than advancing a defined therapeutic candidate. If lncRNAs can be linked causally to differential stress outcomes, they could represent a class of targets for future psychiatric drug development, an area where novel mechanisms remain scarce. The lncRNA field has attracted increasing attention as sequencing technologies have revealed the scale of non-coding transcription across the genome, though translating these findings into actionable biology has proven challenging.