“Members of RFG3 promote research into the mechanisms by which various environmental factors (UV light, ROS-generating chemicals, etc) interact with combinations of genes to produce adverse health effects. An emphasis on UV exposure is particularly relevant to the desert southwest, with Arizona suffering from the highest incidence of skin cancer in the USA.” - Terrence Monks
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The unique environment of the southwest involves extraordinarily high levels of ultraviolet light exposure, leading to degenerative conditions in skin and to skin cancer. Center investigators are studying how environmental factors and micronutrients modulate UV damage.
Investigators/Funding: Bowden (RFG3), Jacobson E (RFG3), Jacobson M (RFG3), Wondrak (RFG3), Zhang (RFG3): NCI/CA43894, NCI/CA106677, NCI/CA122484, NCI/CA27502
- Folate is a nutrient essential for the appropriate control of cellular proliferation, synthesis of new DNA, repair of damaged DNA, and maintenance of epigenetic integrity, all of which are processes critical for skin homeostasis. The Jacobson laboratory is examining the effects of simulated solar light on skin cells as a function of folate status to assess folate as a potential chemoprevention agent.
- Sirtuin expression in the skin is disregulated in response to UV radiation, and modulated by niacin (Jacobson). Multiple niacin dependent pathways have been identified that function to enhance terminal differentiation and the development and maintenance of the skin barrier and genomic stability. Such studies may lead to the identification of new agents to prevent photoaging and skin cancer.
- UVB light promotes survival of initiated keratinocytes, in part, by the direct activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Dr. Bowden has identified quercetin as a novel chemopreventive agent targeting UVB-induced signaling pathways in an effort to reduce the incidence of non-melanoma skin cancer.
- A series of potent cinnamoyl-derived Michael acceptor pharmacophores, including cinnamic aldehyde and methyl-1-cinnamoyl-5-oxo-2-pyrrolidine-carboxylate have been identified as potent inducers of the Nrf2/Keap1-controlled antioxidant response in skin cells (Wondrak and Zhang).