General Research InterestThe role of inflammation, immunosuppressive status, and gender in the development of ultraviolet light induced non-melanoma skin cancer.
Research DescriptionStudies in the Oberyszyn skin carcinogenesis laboratory are designed to increase our understanding of the function of biological mediators including prostaglandins, cytokines and reactive oxygen intermediates during Ultraviolet Light induced Squamous Cell Carcinoma development. Current studies are focused on understanding the differences in male and female skin that contribute to men developing significantly more skin cancer. We are also trying to understand the link between therapeutic or disease induced immunosuppression and the staggering increase in development of non-melanoma skin cancer. In addition we are evaluating both topically applied as well as orally delivered natural compounds such as black raspberry extracts and tomatoes as potential chemopreventive and chemotherapeutic agents.
Transinstitutional WorkWe have several ongoing collaborative efforts both within OSU as well as with investigators at other institutions. Within OSU we are working with Dr. Greg Lesinski (Hematology and Oncology) examining gender differences in the development of myeloid derived suppressor cells (MDSC) and the role these cells play in ultraviolet light induced cutaneous tumor development. MDSC are a heterogeneous population of immature cells of myeloid lineage, which are mobilized from the bone marrow to peripheral lymphoid tissues upon various inflammatory stimuli such as infection, acute and chronic inflammation, sepsis, trauma, and cancer. These cells have been shown to produce immunosuppressive cytokines as well as reactive oxygen and nitrogen species that have been linked to tumor development and progression. Our preliminary studies suggest that gender related differences in the development of these cells might play a key role in tumor burden. Collaborative efforts with Dr. Amanda Toland (MVIMG) are using our murine model as well as human tumors to examine the genetics of skin cancer. These studies are geared towards identifying a genetic profile that could predict cutaneous tumor development in both immunosuppressed patients as well as in the general immunocompetent population. Ongoing studies with Dr. Abhay Satoskar (MVIMG) are focused on identifying the source of macrophage inhibitory factor (MIF) which contributes to pathogenesis of non-melanoma skin cancer to determine whether MIF is a potential therapeutic target in the prevention and treatment of non-melanoma skin cancer and to identify the polymorphism(s) in the MIF gene which may be associated with increased risk of non-melanoma skin cancer. Support from the MCC program and Dr. Steve Clinton are allowing us to begin studies determining the role of Vitamin D in preventing or promoting ultraviolet light induced skin cancer. Additionally, we are carrying out preliminary studies with Dr. Steve Schwartz (Food Sciences) on the effectiveness of tomatoes as a natural orally delivered sunscreen. These studies supported by CAFFRE/MCC funds will be testing the hypothesis that the dietary consumption of tomatoes containing lycopene, phytoene, and phytofluene will reduce skin damage caused by UV radiation as compared to no tomato consumption resulting in decreased development of skin tumors. They are based upon human studies, which have shown that consumption of tomatoes for at least 10 weeks has an inhibitory effect on the UVB-induced inflammatory response in humans. Internationally we have been collaborating with Dr. Gina Rojas, at the University of Concepcion in Chile examining inflammation in the development of lip cancers, a major problem in Chile. We are also collaborating with Dr. Günther Hofbauer from the Dermatology department at the Zurich University Hospital to compare histological changes that occur in the skin of immunosuppressed mice to those that occur in the skin of immunosuppressed patients following acute UV irradiation. Within the US we are collaborating with Dr. Sam Hwang, chair of Dermatology at the Medical College of Wisconsin, to look at alterations in CXCR4 in the skin following UV irradiation and the role that this chemokine receptor may play in non-melanoma skin cancer development and progression. Immunosuppressive molecules expressed on selected cells have the potential to regulate tissue-specific inflammation, and consequently, autoimmunity. Recent studies have revealed that CD200, a potent immunoregulatory protein, is expressed on Langerhans cells and keratinocytes in mouse epidermis. Studies conducted with Dr. Edit Olasz in the Department of Dermatology at the Medical College of Wisconsin, are focused on the effects of ultraviolet light exposure on CD200 expression in the skin and the role that this molecule may play in cutaneous homeostasis and tumor development.