The discoveries made to date and the proposed studies point to an intrinsic role for vitamin D compounds in skin in providing protection from sun damage. As a result of sun exposure, increased concentrations of vitamin D compounds in skin will be generated and this is likely to provide protection against further UV damage, in much the same way as increased pigmentation and increased thickness of the outer layer of skin. Furthermore, the studies are designed to test whether vitamin D compounds wh ....The discoveries made to date and the proposed studies point to an intrinsic role for vitamin D compounds in skin in providing protection from sun damage. As a result of sun exposure, increased concentrations of vitamin D compounds in skin will be generated and this is likely to provide protection against further UV damage, in much the same way as increased pigmentation and increased thickness of the outer layer of skin. Furthermore, the studies are designed to test whether vitamin D compounds which have minimal effects on serum calcium, could nevertheless be used topically in association with a sunscreen or moisturizer to add to sun protection. As Australia has the highest skin cancer rates in the world, this would be of significant health and economic value.Read moreRead less
Mechanisms Of Photoprotection By Vitamin D And Analogs
Funder
National Health and Medical Research Council
Funding Amount
$438,186.00
Summary
Our discoveries have clearly shown that vitamin D compounds produced in skin due to UV exposure, have a role in protecting skin from further UV damage. The studies are designed to further examine the mechanism of this photoprotective effect, as it appears to be novel. This will aid in the developmentof agents, which could be used as an after-sun lotion to gain some protection. As Australia has the highest skin cancer rates in the world, this would be of significant health and economic value.
The Melanoma Susceptibility Gene Product P16 Functions In A UV-induced Cell Cycle Checkpoint In Human Skin
Funder
National Health and Medical Research Council
Funding Amount
$204,131.00
Summary
The contribution of the ultraviolet component of sunlight to skin cancer generally, and melanoma in particular, is widely acknowledged. However, the actual mechanism by which ultraviolet radiation changes the normal skin melanocytes, the pigmented skin cells, into cancerous melanomas is unclear. Several years ago, a gene was identified that was found to be mutated in a high proportion of sporadic melanomas, and was also found to be mutated in a proportion of families with a predisposition to dev ....The contribution of the ultraviolet component of sunlight to skin cancer generally, and melanoma in particular, is widely acknowledged. However, the actual mechanism by which ultraviolet radiation changes the normal skin melanocytes, the pigmented skin cells, into cancerous melanomas is unclear. Several years ago, a gene was identified that was found to be mutated in a high proportion of sporadic melanomas, and was also found to be mutated in a proportion of families with a predisposition to developing melanoma. This melanoma susceptibility gene, p16, can act to block cells growth, thus loss of this gene function in disease could lead to uncontrolled cell growth, a hallmark of cancer. This proposal investiagtes the role of p16 in responses of normal skin cells to ultraviolet radiation. We will examine the increased levels of p16 detected in skin after exposure to low doses of ultraviolet radiation and attempt to define the growth responses of these cells to the increased p16 levels. This project will help to establish the normal role of p16 in cellular responses to ultraviolet radiation, and may also identify novel targets for diagnosis, prevention or treatment of melanoma.Read moreRead less
Quantitiative Assessment Of Solar UV Exposure For Vitamin D Synthesis In Australian Adults
Funder
National Health and Medical Research Council
Funding Amount
$1,162,536.00
Summary
This research program will add significantly to our current scientific understanding of the dual health outcomes of UV exposure (Vitamin D and skin cancer) . This project is in line with Australia's R and D Priorities, in that it will result in direct and indirect social and economic benefits to Australia by applying the scientific knowledge gained through this research to develop public health initiatives to improve some of Australia's most significant and costly health problems.
Susceptibility Of The Basal Layer Of Human Epidermis To UVA Oxidative Damage Due To Pheomelanin And Suboptimal DNA Repair
Funder
National Health and Medical Research Council
Funding Amount
$559,354.00
Summary
Australia has the highest incidence of skin cancer in the world. It is important to understand how sunlight causes skin cancer and the wavelengths involved in order to devise effective preventative and therapeutic strategies. Our proposal is that the cells in the skin that give rise to the most common forms of skin cancer, squamous cell carcinoma and basal cell carcinoma, are particularly vulnerable to UVA. We aim to study why this is the case and whether this vulnerability can be prevented.
Interaction Of Mc1r With The PRb And P53 Pathways In UVR-induced Melanoma Development
Funder
National Health and Medical Research Council
Funding Amount
$553,479.00
Summary
This project will shed light onto fundamental processes causing UV-induced melanoma (MM). Innate differences between individuals, independent of pigmentation, influence MM development. We will study the mechanisms of UVR-induced MM development in mice carrying gene mutations (Cdk4, Arf, Mc1r) that underpin human MM susceptibility. Knowledge of the sensitivity of an one's MCs to UV could be critical for targeting susceptible groups for health education campaigns and more intense screening.
NEURAL MODULATION OF HEARING LOSSES INDUCED BY LOUD SOUND
Funder
National Health and Medical Research Council
Funding Amount
$290,500.00
Summary
Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with ....Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with a view to optimising such mechanisms. I propose to build on seminal Australian work to examine how one such system, nerves from the brain to the inner ear (the site of most damage from loud sounds), modulates hearing losses caused by loud sounds. Early studies indicated these nerves could protect from damage induced by short-lasting loud sound and this has led to international interest in functional applications of such protection to reduce hearing damage suffered by humans. However, my recent work indicates the nerves exert complex protective and exacerbative effects to loud sounds similar to common trauma or occurring under conditions similar to common trauma. They even exacerbate hearing losses due to loud sound, especially when there is an imbalance in hearing sensitivity in the two ears (bilateral) similar to what is common in humans. These findings make it critical that functional application be delayed until the full range of effects exerted by the nerves is understood. I propose to elucidate the novel complex effects of these nerves to loud sound. Specific aims are: (1) To understand effects of these pathways to loud sounds like those encountered by humans, (2) To investigate how chronic imbalanced bilateral hearing sensitivity, like that common in humans, alters effects of the nerves and when they change from being protective to exacerbative, (3) To adduce how an atraumatic sound affects hearing losses due to later loud sound and the role played by these nerves.Read moreRead less