Monday, April 28, 2025
4/28/2025
MOLECULAR ANALYSIS OF SCARLESS FETAL WOUND HEALING - DESCRIPTION (provided by applicant): Adult mammalian tissues respond to injury by healing with scar formation. Scar tissue assists in sealing a wound, but can also lead to significant morbidity. Scar can restrict tendon and muscle movement, obstruct visceral lumens, and impede peripheral nerve regeneration. In the head and neck especially scarring can have severe consequences, causing hearing loss, loss of smell and taste, loss of voice and articulation, airway obstruction, as well as the obvious stigma of gross visible deformity. In contrast to adults, mammalian fetuses are known to heal without scar in a process akin to regeneration. This remarkable ability is known to be intrinsic to fetal tissues, independent of the uterine environment, and is lost in the third trimester of gestation. An understanding of the biological basis for scarless healing might well lead to new strategies to limit the morbidity of scar. We hypothesize that scarless fetal wound healing drives from a subset of differentially expressed genes in fetuses versus adults. The aims of this project are to establish microarrays that encompass the full relevant gene set comprising the expressomes of healing fetal and adult wounds, to identify differentially regulated genes, to better characterize selected differentially regulated gene products, and to confirm differential expression at the protein level through a proteomics approach. We will evaluate promising candidate genes thus identified for their biological significance in a number of model systems, including transgenic and knockout animals, and through the use of somatic gene transfer. We will also investigate possible mechanisms controlling the fetal wound-specific downregulation of the eta chaperonin subunit. With these complementary approaches we hope to thereby arrive at a broad understanding of the gene patterns controlling both fetal and adult wound healing, and identify gene products/pathways critical to both.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).