Restoration of cutaneous function within the body's largest organ in the wake of unplanned trauma inflicted by burns, lacerations, pathologic organisms, UV exposure, ischemia, iatrogenic agents, environmental toxins or planned surgical incisions/excisions remains a perpetual challenge. EGF receptor-activated mechanisms governing either epidermal proliferation or migration following cutaneous trauma continue to be our central focus.
Aim 1 Studies will define key responses along the prototypic EGF/EGFR pathway that differentiate between a poliferative and/or migratory phenotype in wounded epidermis. Laser capture microdissection techniques will be used to select discrete cell populations for gene expression analyses of EGF-like ligands and different ErB receptor types.
In Aim 2 Studies, an integrative microarray analysis approach will establish temporal positioning of receptor tyrosine kinases RTKs, their ligands and influential gene expression patterns between proliferating and migrating epidermal cells will be defined by combining the power of laser capture microdissection techniques with global screening options by gene microarrays.
Aim 3 studies will continue to build in vivo strategies for enhancing wound repair by boosting receptor tyrosine kinases. Using an adenoviral transfection delivery system in the porcine wound model, we will manipulate repair by boosting gene heterodimer partners c) sequential introduction of unrelated receptor tyrosine kinases (RTKs) over the course of the repair process. Effective manipulation of wound repair in terms of health care dollars and chronic human suffering is staggering. To accomplish this objective, we will primarily focus on the EGF/EGFR/Signaling Tranduction Pathways that are evoked in response to cutaneous trauma. The focal pathway will remain the prototypic cluster with the greatest RTK family - EGF-like ligand family and 4 EGF receptors forms will remain the focal pathway for our studies. This proposal places the spotlight on genes that control either a migratory or a poliferative phenotype within the complex human wound environment.
| Greco 3rd, J A; Pollins, A C; Boone, B E et al. (2010) A microarray analysis of temporal gene expression profiles in thermally injured human skin. Burns 36:192-204 |
| Caldwell, Robert L; Opalenik, Susan R; Davidson, Jeffrey M et al. (2008) Tissue profiling MALDI mass spectrometry reveals prominent calcium-binding proteins in the proteome of regenerative MRL mouse wounds. Wound Repair Regen 16:442-9 |
| Nanney, Lillian B; Woodrell, Christopher D; Greives, Mathew R et al. (2008) Calreticulin enhances porcine wound repair by diverse biological effects. Am J Pathol 173:610-30 |
| Pollins, Alonda C; Friedman, David B; Nanney, Lillian B (2007) Proteomic investigation of human burn wounds by 2D-difference gel electrophoresis and mass spectrometry. J Surg Res 142:143-52 |
| Caldwell, Robert L; Opalenik, Susan R; Davidson, Jeffrey M et al. (2007) Tissue profiling MALDI mass spectrometry reveals prominent calcium-binding proteins in the proteome of regenerative MRL mouse wounds. Wound Repair Regen : |
| Okwueze, Martina I; Cardwell, Nancy L; Pollins, Alonda C et al. (2007) Modulation of porcine wound repair with a transfected ErbB3 gene and relevant EGF-like ligands. J Invest Dermatol 127:1030-41 |
| Ajmal, Nadeem; Riordan, Colin L; Cardwell, Nancy et al. (2003) Chemically assisted capsulectomy in the rabbit model: a new approach. Plast Reconstr Surg 112:1449-54; discussion 1462-3 |
| Draper, Bradley K; Komurasaki, Toshi; Davidson, Mari K et al. (2003) Topical epiregulin enhances repair of murine excisional wounds. Wound Repair Regen 11:188-97 |
| Ajmal, Nadeem; Riordan, Colin L; Cardwell, Nancy et al. (2003) The effectiveness of sodium 2-mercaptoethane sulfonate (mesna) in reducing capsular formation around implants in a rabbit model. Plast Reconstr Surg 112:1455-61; discussion 1462-3 |
| Milatovic, Snjezana; Nanney, Lillian B; Yu, Yingchun et al. (2003) Impaired healing of nitrogen mustard wounds in CXCR2 null mice. Wound Repair Regen 11:213-9 |
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