Identification and non-invasive measurement of biomarkers of radiation exposure in human skin
Active Cooperative Agreement Awarded Last action
- Award ID
- U01AI189403
- Recipient
-
Brigham & Womens Hospital Inc. UEI QN6MS4VN7BD1 Part of Partners Healthcare System Incorporated
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,205,698
Award facts
- Assistance listing
- 93.310 Trans-NIH Research Support
- Completion date 23% complete
- Funding agency
- Office of the Director National Institutes of Health, Department of Health and Human Services
- Place of performance
- Boston, MA 02115, USA
Award details come from USAspending.gov.
Description
- Abstract
- Abstract: the skin is a barrier tissue that is impacted by all types of external radiation events and is accessible to non- invasive testing. Tape stripping of the skin is an effective, well established, and non-invasive method for sampling both protein and RNA biomarkers in human skin. We have developed a model of studying radiation injury in human skin by irradiating living human skin grafts carried by immunodeficient NSG mice. Our model recapitulates both the early inflammatory and late fibrotic changes in skin observed in patients after radiation exposure. We present pilot spatial profiling and immunostaining data demonstrating that superficial keratinocytes, the cell population sampled by non-invasive tape stripping, upregulate RNA and protein biomarkers within 24 hours of radiation exposure and that different biomarkers have the potential to discriminate between 1, 2 and 5 GY radiation. In this proposal, we will identify optimal keratinocyte biomarkers of radiation exposure and develop a point-of-care test to measure them using non-invasive tape stripping. In aim 1, we will identify, validate and measure the expression kinetics of keratinocyte biomarkers of radiation exposure (0, 1, 2, 5 GY) in human skin grafts carried by NSG mice. Xenium 5000 plex spatial transcriptional profiling will be used to identify candidate biomarkers (aim 1A), followed by single cell proteomic measurement of candidate biomarkers using cyclic immunofluorescence (cycif) in both discovery and validation sample cohorts (aim 1B, c). The kinetics of protein biomarker expression will then be evaluated via cycif on days 1, 2, 3, 5, and 7 after 1, 2, or 5 GY irradiation (aim 1D). In aim 2, we will use NSG mice grafted with neonatal foreskin and skin obtained from aged patients (>65 years) to study the utility of identified biomarkers in pediatric and aged individuals. In aim 3, we will develop and test a point-of-care test to measure biomarkers using non-invasive tape stripping of the skin. These studies will generate validated, human cutaneous biomarkers of radiation exposure and a non-invasive test to measure them that is immediately applicable to the care of humans exposed to radiation.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $589,496 | |
| Original award | $616,202 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Arizona State University | $102,837 |
Quick answers
Who received award U01AI189403?
U01AI189403 was awarded to Brigham & Womens Hospital Inc. by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on September 1, 2025.
How much is award U01AI189403 worth?
$1,205,698 has been obligated on U01AI189403.
Which agency awarded U01AI189403?
National Institute of Allergy and Infectious Diseases (National Institutes of Health) awarded U01AI189403, with funding from Office of the Director (National Institutes of Health).
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