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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
3R33AI080604-04S1
Application #
8531403
Study Section
Special Emphasis Panel (NSS)
Program Officer
Dicarlo-Cohen, Andrea L
Project Start
2008-07-15
Project End
2014-02-28
Budget Start
2012-08-21
Budget End
2013-02-28
Support Year
4
Fiscal Year
2012
Total Cost
$113,871
Indirect Cost
$39,916
Name
University of California Davis
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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
Dasu, Mohan R; Ramirez, Sandra R; La, Thi Dinh et al. (2014) Crosstalk between adrenergic and toll-like receptors in human mesenchymal stem cells and keratinocytes: a recipe for impaired wound healing. Stem Cells Transl Med 3:745-59
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
Yang, Hsin-ya; La, Thi Dinh; Isseroff, R Rivkah (2014) Utilizing custom-designed galvanotaxis chambers to study directional migration of prostate cells. J Vis Exp :
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
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 β2-adrenergic receptor-mediated upregulation of IL-6. J Invest Dermatol 134:809-17
Babalola, Olubukola; Mamalis, Andrew; Lev-Tov, Hadar et al. (2014) NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents. Arch Dermatol Res 306:313-30
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
Babalola, Olubukola; Mamalis, Andrew; Lev-Tov, Hadar et al. (2013) The role of microRNAs in skin fibrosis. Arch Dermatol Res 305:763-76

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