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Integrated spatial omics to elucidate conserved inflammatory mechanisms of vesicant-induced skin injury

Award Number: R34AR084669
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/17/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Integrated spatial omics to elucidate conserved inflammatory mechanisms of vesicant-induced skin injury - SUMMARY Despite significant research and investment, no FDA approved broad spectrum countermeasures are available to rapidly mitigate vesicant-induced injury following intentional or accidental chemical exposure. Inflammatory pathways are a promising shared target for therapeutic intervention as: (1) inflammatory mechanisms may be conserved across multiple vesicants as inflammatory damage is present in all types of burns; (2) burn injury is not static, inflammatory damage continues to occur up to 72 hours after exposure and there is potential to arrest inflammatory damage and necrosis with early anti-inflammatory intervention; and (3) there is an existing portfolio of anti-inflammatory therapies and an active drug development pipeline that can be applied and optimized. Current approaches to investigate inflammatory mechanisms in skin lack integration of mechanistic and spatial information. Systemic fluid readouts may not accurately reflect local burn response and all spatial information is lost when skin biopsies are homogenized for traditional omics analyses. Histological analysis of biopsies can provide spatial information regarding tissue damage but lacks mechanistic insight. Therefore, novel spatial omics approaches that provide in situ understanding of the pathological response will be important tools in the discovery and development of medical countermeasures to vesicant-induced damage. The long-term objective of this research is to implement and establish a state-of-the-art spatial multi-omics platform to investigate conserved mechanisms of inflammatory damage induced by cutaneous exposure of sulfur mustard and lewisite vesicants in a clinically relevant porcine skin model. Utilizing innovative methods in spatial mass spectrometry, MALDI mass spectrometry imaging (MALDI-MSI), immunohistochemistry, and spatial transcriptomics we will map the distribution of transcriptional pathways and biomediators associated with localized vesicant-induced skin damage. The specific aims of this study are to 1) Identify the inflammatory phenotypes induced in response to dermal exposure to sulfur mustard and lewisite; and 2) Use high resolution spatial transcriptomics integrated with MALDI-MSI and immunohistochemistry to identify pathologic programs conserved across sulfur mustard and lewisite burn lesions. Our proposed spatial mapping approach will allow us to decipher the local inflammatory pathological effects of vesicants not evident in systemic studies and thus elucidate conserved pathologic inflammatory pathways that drive tissue damage and can be targeted for the development of medical countermeasures.


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 = $182,240 )
2025	2025	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	8/12/2025	NON-COMPETING CONTINUATION	$182,240
2025	2024	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/12/2025	NEW	$0
														Subtotal = $182,240

Issue Date FY: 2024 ( Subtotal = $317,240 )
2024	2024	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/17/2024	NEW	$317,240
														Subtotal = $317,240

Grand Total All Awards = $499,480

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Integrated spatial omics to elucidate conserved inflammatory mechanisms of vesicant-induced skin injury

Award Number: R34AR084669

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/17/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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