Wednesday, February 5, 2025 2/5/2025

Transposable elements in the keratinocyte genome and their regulation during skin development and epidermal differentiation

Award Number: R01AR078306
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

PROJECT SUMMARY Ethnic disparities represent a significant problem in modern dermatology, and additional efforts are required to better understand mechanisms underlying the development of skin diseases in patients with skin of color. Inflammatory skin conditions (acne, atopic dermatitis, hidradenitis suppurativa) represent a group of diseases, which disproportionally impact African American (AA) patients including children. Comparative transcriptome analyses of the skin reveal higher expression of multiple inflammation-related genes in AA healthy individuals compared to non-Hispanic White (NHW) individuals. Regulation of expression of the genes involved in inflammatory skin response occurs at several levels including signaling/transcription factor-mediated and epigenetic mechanisms. Transposable elements (TEs) are repetitive mobile segments of DNA that constitute 44%-55% of mouse or human genomes. Inappropriate TE activation has been implicated in pathogenesis of over 120 human diseases including autoimmune disorders. Most TEs are transcriptionally inactive, while their aberrant activation result in a production of double- stranded (ds) RNA and dsDNA triggering the dsRNA/DNA sensing mechanisms followed by anti-viral immune response. In the epidermis, UV exposure activates transcription of endogenous retroviral sequences. Endogenous retroviruses of the HERV-K and W families are significantly upregulated in psoriatic versus non- lesional skin. However, contribution of TEs to regulation of skin inflammation in AA individuals remain unknown. In this Administrative Supplement application to AR078306-03 grant, we will test a hypothesis that aberrant activation of TEs in epidermal keratinocytes serve as critical determinant driving inflammatory skin response in individuals with understudied skin types, while pharmacological inhibition of the TE transcription with the nucleoside reverse transcriptase inhibitors provides a novel strategy for management of inflammatory skin conditions in these individuals. This hypothesis will be addressed via two Specific Aims: 1. Perform comparative analyses of the landscapes of transposable element expression in human epidermal keratinocytes between understudied skin types and NHW skin and correlate these data with gene expression and patterns of active/repressive covalent DNA/histone modifications. 2. Define the effects of the inhibitors of dsRNA and dsDNA pathways on expression of inflammation- associated genes in epidermal keratinocytes isolated from understudied skin types in 3D skin equivalent culture and in experimental in vitro models of skin inflammation. The generated outputs from this application will provide novel insights into fundamental mechanisms regulating inflammation in understudied human skin types, as well as will promote the development of novel paradigms for management of skin inflammatory responses in humans via modulation of TE activities.


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: 2025 ( Subtotal = $423,238 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	12/23/2024	NON-COMPETING CONTINUATION	$423,238
														Subtotal = $423,238

Issue Date FY: 2024 ( Subtotal = $713,140 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	5/31/2024	NON-COMPETING CONTINUATION	$33,602
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	2/7/2024	SUPPLEMENT FOR EXPANSION	$247,500
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	2/5/2024	NON-COMPETING CONTINUATION	$432,038
														Subtotal = $713,140

Issue Date FY: 2023 ( Subtotal = $488,897 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/26/2023	NON-COMPETING CONTINUATION	$440,007
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	4/24/2023	NON-COMPETING CONTINUATION	$48,890
														Subtotal = $488,897

Issue Date FY: 2022 ( Subtotal = $486,628 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	2/2/2022	NON-COMPETING CONTINUATION	$442,388
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	5/30/2022	NON-COMPETING CONTINUATION	$44,240
														Subtotal = $486,628

Issue Date FY: 2021 ( Subtotal = $506,307 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/16/2021	NEW	$506,307
														Subtotal = $506,307

Grand Total All Awards = $2,618,210

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Transposable elements in the keratinocyte genome and their regulation during skin development and epidermal differentiation

Award Number: R01AR078306

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer