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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08DE014780-01A2
Application #
6726474
Study Section
Special Emphasis Panel (ZDE1-LK (62))
Program Officer
Hardwick, Kevin S
Project Start
2003-07-28
Project End
2008-05-31
Budget Start
2003-07-28
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$124,927
Indirect Cost
Name
Allegheny-Singer Research Institute
Department
Type
DUNS #
033098401
City
Pittsburgh
State
PA
Country
United States
Zip Code
15212
Kathju, Sandeep; Nistico, Laura; Melton-Kreft, Rachael et al. (2015) Direct demonstration of bacterial biofilms on prosthetic mesh after ventral herniorrhaphy. Surg Infect (Larchmt) 16:45-53
Kathju, Sandeep; Nistico, Laura; Tower, Irene et al. (2014) Bacterial biofilms on implanted suture material are a cause of surgical site infection. Surg Infect (Larchmt) 15:592-600
Stoodley, Paul; Conti, Stephen F; DeMeo, Patrick J et al. (2011) Characterization of a mixed MRSA/MRSE biofilm in an explanted total ankle arthroplasty. FEMS Immunol Med Microbiol 62:66-74
Kathju, Sandeep; Lasko, Leslie-Ann; Nistico, Laura et al. (2010) Cutaneous fistula from the gastric remnant resulting from a chronic suture-associated biofilm infection. Obes Surg 20:251-6
Kathju, Sandeep; Cohen, Ruben; Lasko, Leslie-Ann et al. (2010) Pseudogout of the temporomandibular joint: immediate reconstruction with total joint arthroplasty. Head Neck 32:406-10
Stoodley, Paul; Braxton Jr, Ernest E; Nistico, Laura et al. (2010) Direct demonstration of Staphylococcus biofilm in an external ventricular drain in a patient with a history of recurrent ventriculoperitoneal shunt failure. Pediatr Neurosurg 46:127-32
Satish, Latha; Johnson, Sandra; Wang, James H-C et al. (2010) Chaperonin containing T-complex polypeptide subunit eta (CCT-eta) is a specific regulator of fibroblast motility and contractility. PLoS One 5:e10063
Tower, Irene; Lasko, Leslie-Ann; Kathju, Sandeep (2010) Secondary surgery for cicatricial complications of facial injury. J Oral Maxillofac Surg 68:751-5
Satish, Latha; Hogg, Justin; Johnson, Sandra et al. (2010) Expression of receptor for activated C kinase 1 in healing skin and mucosal wounds. Ann Plast Surg 64:238-41
Kathju, Sandeep; Nistico, Laura; Hall-Stoodley, Luanne et al. (2009) Chronic surgical site infection due to suture-associated polymicrobial biofilm. Surg Infect (Larchmt) 10:457-61

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