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Dysregulating brain transposable elements to study stress-induced social behaviors and gene expression

Award Number: F31MH143414
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Dysregulating brain transposable elements to study stress-induced social behaviors and gene expression - PROJECT SUMMARY/ABSTRACT This proposal aims to elucidate a potential neurobiological mechanism of stress-induced social behavior deficits. Chronic stress is well-known to contribute to neuropsychiatric disorders such as major depressive disorder and post-traumatic stress disorder, and social dysfunction is often cited by patients as a major quality of life problem. Based on previous work from the lab, transposable element (TE) dysregulation has been identified as a driver of social behavior deficits in stress- naïve mice. TEs are known to be silenced in the genome by KRAB zinc finger protein (KZFP) transcription factors, which collectively bind the transcriptionally repressive cofactor TRIM28. Using novel synthetic TRIM28 variants delivered into the medial prefrontal cortex (mPFC) of male and female mice, this study will probe the connection between chronic stress, mPFC TE stability, and social behavior. The synthetic TRIM28 variants, TRIM28WT and TRIM28VPR, exert opposing forms of transcriptional control, with TRIM28WT acting as a gene repressor and TRIM28VPR as an activator. Aim 1 seeks to determine the behavioral outcomes of applying synthetic TRIM28 variants to mice who have undergone chronic social stress, thereby providing training in the application of translationally relevant chronic stress paradigms. Restabilizing TEs via TRIM28WT is predicted to reverse stress-induced social behavior deficits. Aim 2 seeks to characterize the mPFC transcriptional correlates of these behaviors, in terms of both canonical genes and TEs, using bulk RNA sequencing of microdissected mPFC tissue. Moreover, Aim 2 will relate these gene transcriptional changes to known changes induced by chronic social stress in the absence of TRIM28 manipulations. This will clarify the gene and TE transcriptional responses to chronic stress and will provide training in the analysis of complex bioinformatic data. Collectively, this project aims to understand the role of TE stability in the mPFC in stress-induced social behavior deficits, ideally culminating in a novel approach to address the gap in quality of life for people with chronic stress associated neuropsychiatric disorders.


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 = $45,530 )
2026	2026	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Mental Health Research Grants	001	1	6/19/2026	NEW	$0
2026	2026	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Mental Health Research Grants	000	1	6/19/2026	NEW	$45,530
														Subtotal = $45,530

Grand Total All Awards = $45,530

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Dysregulating brain transposable elements to study stress-induced social behaviors and gene expression

Award Number: F31MH143414

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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