We will investigate combined injury by moderate dose radiation in two models in a two- phase study. In the first phase, we will use anonymized surgical samples irradiated and wounded ex vivo by burning to study gene and protein expression differences, develop a non-invasive assay to predict successful wound healing, and test a beta adrenergic receptor antagonist as potential therapy to improve wound healing. In the second phase, we will investigate similar issues in a mouse model. Thus, the total study will combine human data (which is, however, not in vivo) and data from intact animals (which is in vivo) to obtain relevant information that can inform the development of a better mechanistic understanding of the mechanisms of wound healing in the presence of radiation damage, and to develop potential therapies that can later be tested in the clinic.
In a nuclear warfare or terrorist incident, combined injury by radiation and burn wounding is likely. We will provide a better mechanistic understanding of the molecular biology behind healing of combined injury wounds, and will test a non-invasive assay for wound healing success and a potential therapy to improve healing. All of this would be of considerable public health benefit in such a scenario.
|Sivamani, Raja K; Shi, Biao; Griffiths, Elizabeth et al. (2014) Acute wounding alters the beta2-adrenergic signaling and catecholamine synthetic pathways in keratinocytes. J Invest Dermatol 134:2258-66|
|Mamalis, Andrew; Fiadorchanka, Natallia; Adams, Lauren et al. (2014) An immunohistochemical panel to assess ultraviolet radiation-associated oxidative skin injury. J Drugs Dermatol 13:574-8|
|Kim, Min-Ho; Gorouhi, Farzam; Ramirez, Sandra et al. (2014) Catecholamine stress alters neutrophil trafficking and impairs wound healing by ?2-adrenergic receptor-mediated upregulation of IL-6. J Invest Dermatol 134:809-17|
|Mamalis, A D; Lev-Tov, H; Nguyen, D-H et al. (2014) Laser and light-based treatment of Keloids--a review. J Eur Acad Dermatol Venereol 28:689-99|
|Babalola, Olubukola; Mamalis, Andrew; Lev-Tov, Hadar et al. (2014) Optical coherence tomography (OCT) of collagen in normal skin and skin fibrosis. Arch Dermatol Res 306:1-9|
|Mamalis, Andrew; Garcha, Manveer; Jagdeo, Jared (2014) Targeting the PD-1 pathway: a promising future for the treatment of melanoma. Arch Dermatol Res 306:511-9|
|Babalola, Olubukola; Mamalis, Andrew; Lev-Tov, Hadar et al. (2013) The role of microRNAs in skin fibrosis. Arch Dermatol Res 305:763-76|
|Albrecht, Huguette; Durbin-Johnson, Blythe; Yunis, Reem et al. (2012) Transcriptional response of ex vivo human skin to ionizing radiation: comparison between low- and high-dose effects. Radiat Res 177:69-83|