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Using human skin grafted mice to identify biomarkers of exposure and study effects of radiation on skin

Award Number: U01AI148306
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Summary/Abstract In the event of a large scale radiologic or nuclear event, the immediate needs are to discriminate exposed individuals from the worried well and identify individuals at risk for radiation-induced tissue damage. Humans vary in their sensitivity to radiation-induced tissue injury, the factors that control radiation sensitivity are not fully understood, and there are no biomarkers to identify individuals at risk for radiation-induced tissue damage. The skin is an immunologically active barrier tissue that will be impacted by all types of external radiation events. Skin is visually observable, accessible to non-invasive testing and easily sampled, making it amenable to a variety of testing modalities. We propose to irradiate and study living, immunologically intact human skin grafts on immunodeficient NSG mice to identify biomarkers that detect exposure to radiation and predict radiation induced tissue damage. In Aim 1, we will study the effects of irradiation on adult human skin grafts carried by NSG mice. We will study DNA damage repair proteins, reactive oxygen species, epithelial barrier function and gene expression changes in adult human skin grafts exposed to 0, 0.5, 1.0, 2.0 or 5.0 Gy irradiation. We will identify biomarkers that detect radiation exposure within 24 hours of exposure (Phase I), remain detectable longer term and/or correlate with later tissue injury (Phase II) and we will validate these biomarkers in a separate validation cohort of 30 human skin donors (Phase III). In Aim 2, we will study the effects of irradiation on human neonatal foreskin grafts, a tissue that contains antigen presenting cells but lacks T cells, as a model for both pediatric and immunocompromised populations. We will test biomarkers identified in Aim 1 for their ability to detect radiation exposure within 24 hours and to predict tissue injury in neonatal foreskin. If necessary, we will identify new biomarkers for use in pediatric and immunocompromised populations. In Aim 3, we will develop rapid point-of-care tests to detect the biomarkers we identify in Aims 1 and 2. The skin is an accessible tissue that can be studied as a proxy to predict the risk of radiation-induced injury at other tissue sites. By studying immunologically intact skin from a diverse population of human donors, we will identify biomarkers that are useful in i) humans, ii) a diverse, outbred population with differing sensitivities to radiation, and iii) pediatric and immunocompromised populations. Identification of biomarkers that predict subsequent tissue damage in skin will identify radiation sensitive individuals. Our point-of-care tests have the potential to rapidly screen potentially exposed populations and identify individuals who are at risk for tissue damage and will require further medical attention.


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: 2024 ( Subtotal = $455,542 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	1/26/2024	NON-COMPETING CONTINUATION	$455,542
														Subtotal = $455,542

Issue Date FY: 2023 ( Subtotal = $609,209 )
2023	2023	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	1/20/2023	NON-COMPETING CONTINUATION	$509,209
2023	2023	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	4	7/26/2023	NON-COMPETING CONTINUATION	$100,000
														Subtotal = $609,209

Issue Date FY: 2022 ( Subtotal = $507,698 )
2022	2022	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	1/13/2022	NON-COMPETING CONTINUATION	$507,698
2022	2022	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	003	3	5/31/2022	NON-COMPETING CONTINUATION	$0
2022	2021	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	2	5/31/2022	NON-COMPETING CONTINUATION	$0
2022	2020	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	1	5/31/2022	NEW	$0
														Subtotal = $507,698

Issue Date FY: 2021 ( Subtotal = $534,914 )
2021	2021	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	1/28/2021	NON-COMPETING CONTINUATION	$534,914
														Subtotal = $534,914

Issue Date FY: 2020 ( Subtotal = $540,530 )
2020	2020	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	2/21/2020	NEW	$540,530
														Subtotal = $540,530

Grand Total All Awards = $2,647,893

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Using human skin grafted mice to identify biomarkers of exposure and study effects of radiation on skin

Award Number: U01AI148306

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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