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Do ‘classical’ Or ‘oxidative’ UVR-induced DNA Adducts Drive Melanoma Induction After Ultraviolet Radiation
Funder
National Health and Medical Research Council
Funding Amount
$335,757.00
Summary
There is debate about the mechanisms by which sun exposure influences melanoma development. This leads to difficulties in formulating adequate sunscreens and guidelines for safe levels of exposure. We will elucidate the critical UV-induced DNA adducts that are necessary for MM development. This will introduce experimental evidence into the debate about sun exposure and melanoma. The use of post sunburn creams containing enzymes which rapidly remove the dangerous DNA adducts will be indicated.
There is a need for a greater understanding of the complex relationship between sun exposure and the production of Vitamin D. This study will expand on the recently-completed AusD study to examine how personal, behavioural, and environmental factors impact on intra-individual seasonality in Vitamin D production. The study findings will guide the development of specific, evidence-based public health recommendation that balance the risks and benefits of sun exposure.
Squamous cell carcinoma of the skin is extremely common in Australia, resulting in disfiguring surgeries and deaths. Although cumulative sun exposure is important, some people are very susceptible, and we do not know why. This project hinges on the notion that skin cancer is a complex (many genes involved). We will utilize novel systems to harness this complexity to understand why some people are resistant and others very susceptible so as to design appropriate control measures and treatments.
Fighting Epidermal Skin Cancers By Targeting Epidermal Clones That Accumulate Mutations
Funder
National Health and Medical Research Council
Funding Amount
$1,149,373.00
Summary
Common skin cancers such as basal and squamous cell carcinomas (BCC and SCC) are by far the most frequent cancer worldwide and require over a million interventions per year in Australia. This project will identify the skin cells that are most susceptible to give rise to cancer if excessively exposed to the sun and explores ways to prevent cancer formation. This will inform on new strategies to prevent new skin cancer development.
Tracking Epidermal Clonal Evolution During Skin Cancer Induction And Progression
Funder
National Health and Medical Research Council
Funding Amount
$558,168.00
Summary
Skin cancer is the most frequent form of cancer in Australia and in many parts of the world. It is strongly connected to ultraviolet radiation from the sun. In this project, we will use our capacity to track individual cells, to observe the heterogeneity of tumours and the lesions that precede them. We will show the importance of this heterogeneity in tumour progression unveiling the limits of current therapies against skin cancer.
Synthetic Lethality Screen Targeting A Defective Checkpoint In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$552,121.00
Summary
All cancers have defects in the mechanisms that regulate normal cell growth and division. These defects provide a growth advantage for the cancer, but can also be an Achilles Heel. In this project we will investigate targeting a defective control mechanism we found in a high proportion of melanomas. We will identify genes that when inhibited combine with the defective control to specifically kill tumour cells with this defect. Normal tissue is protected by its intact regulatory mechanism.
Is CYP11A1 Critical For The Vitamin D Photoprotective System In Skin?
Funder
National Health and Medical Research Council
Funding Amount
$517,567.00
Summary
Sunlight produces DNA damage. When inadequately repaired, this damage produces skin cancer. The vitamin D system in skin helps protect against this skin damage, but the vitamin D compounds involved and how they work is unclear. Recent data shows new vitamin D compounds with photoprotective activity and that vitamin D compounds increased expression of DNA repair proteins. These studies may enable pharmacological enhancement of protection from sunlight.
Identifying The Mechanism Of The G2 Phase UV Checkpoint And Repair Response Commonly Defective In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$569,656.00
Summary
The UV component of sunlight is the major environmental factor driving the development of melanoma. UV radiation can directly mutate genes resulting in their inability to perform normal functions which may contribute to cancer. Despite the high number of mutations directly attributable to UV radiation, the mechanisms known to repair these mutations are generally normal in melanoma. This research will investigate a repair mechanism we have identified that is commonly defective in melanomas.
Narrow Band UVB Phototherapy For Patients With Clinically Isolated Syndrome: A Phase 1 Trial
Funder
National Health and Medical Research Council
Funding Amount
$682,803.00
Summary
The environment, particularly lack of sunlight exposure, contributes to the incidence and progression of multiple sclerosis. We will give patients with early multiple sclerosis controlled exposure to ultraviolet light and then measure biomarkers of their disease activity over the next 12 months. The therapy is safe and is used for treatment of patients with psoriasis. Patients should gain benefits from sunlight-induced vitamin D, as well as other sunlight-induced molecules.
Brm And Brg-1 Protect From Ultraviolet Radiation-induced Skin And Ocular Damage
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Ultraviolet radiation within sunlight is the most important environmental hazard to which Australians are exposed. It causes cancers of the skin and eye, in addition to other forms of skin and eye damage. However sunlight also has health benefits such as vitamin D production. To protect our health from the sun we need to understand how it causes damage and the meachanisms involved. We have discovered a new pathway that we plan to study, called Brm and Brg-1, that provides protection from UV.