Ligand Interactions Of The MC1R Receptor And Cellular Consequences For Melanocyte Responses To UV-damage
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
Although it is evident that fair skin types are more susceptible to sun damage, the relationship between sun exposure, skin colour and skin cancer formation is less clear. The genes and processes that determine an individual's skin phototype and the mechanisms involved in the tanning response after UV-exposure of the skin are the focus of this investigation. A major regulator of the response to UV radiation in the skin is the melanocortin-1 receptor. It is essential to understand the complex int ....Although it is evident that fair skin types are more susceptible to sun damage, the relationship between sun exposure, skin colour and skin cancer formation is less clear. The genes and processes that determine an individual's skin phototype and the mechanisms involved in the tanning response after UV-exposure of the skin are the focus of this investigation. A major regulator of the response to UV radiation in the skin is the melanocortin-1 receptor. It is essential to understand the complex interactions of this receptor that induce tanning.Read moreRead less
Modulating Inflammation As A Therapy For Harlequin Ichthyosis
Funder
National Health and Medical Research Council
Funding Amount
$718,739.00
Summary
Harlequin Ichthyosis is a severe inherited skin disease caused by mutations in a protein which regulates how skin cells control their levels of lipids. Treatments for this disease are limited and do little to improve patients condition. We believe we have found a new way to treat this condition by altering tissue inflammation. This grant will undertake important experiments aimed at developing new therapies for this currently incurable disease.
Defining The Mechanisms Regulating Tissue Mechano-reciprocity In Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$624,488.00
Summary
Wound healing is slow in people with diseases including diabetes or reduced blood circulation to the limbs. Wounds that remain unhealed for a long time may require surgery and limb amputations, often leading to disability and premature death, while costing the health system $3 billion/yr. We have found that wound healing can be accelerated more than 2-fold by the inhibition of a protein called 14-3-3zeta, and seek to find out how this occurs so that it may be exploited for therapy.
Identification Of Clinically Significant Subtypes Of Head And Neck Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$469,122.00
Summary
Squamous cell carcinoma of the head and neck region (HNSCC) is amongst the top 10 most prevalent cancers. It is a life threatening cancer that is associated with a mortality rate of approximately 40%. Whilst most patients are treated with a combination of surgery, radiation and chemotherapy a significant fraction of patients relapse and eventually succumb to the cancer. The molecular basis for relapse in these patients is still unknown. One possible explanation for treatment failure is the notio ....Squamous cell carcinoma of the head and neck region (HNSCC) is amongst the top 10 most prevalent cancers. It is a life threatening cancer that is associated with a mortality rate of approximately 40%. Whilst most patients are treated with a combination of surgery, radiation and chemotherapy a significant fraction of patients relapse and eventually succumb to the cancer. The molecular basis for relapse in these patients is still unknown. One possible explanation for treatment failure is the notion that the cancer contains biologically distinct subtypes of cancer cells. Some these cells may respond to therapy whilst a small fraction of cells may not. If this small fraction of resistant cells were able to divide and repopulate the tissue then this would provide an explanation for relapse in these patients. However, as yet no such data has been available to support this argument. Most recently, studies with another cancer called acute myelocytic leukaemia has shown that they do contain a small subtype of cancer cells that are resistant to therapy and can regenerate the disease in patients. These cells have been called tumour initiating cells (TIC). In this application we will use patient tumour samples to try to isolate TICs from HNSCC. We will first determine whether these TICs exist and whether they express markers of normal human stem cells. We will also test whether these TICs are more resistant to chemotherapeutics or radiation than the rest of the tumour cells. In addition we will enrich for these TICs and identify new protein markers that could be used to test patient samples before or after treatment. This would be of considerable assistance in making decisions about treatment choice or prognosis. Since TICs have not been reported in HNSCC previously their identification would lead to a considerable advance in our undesratnding of how these tumours form.Read moreRead less
Mechanism And Treatment Of Sympathetically Maintained Pain
Funder
National Health and Medical Research Council
Funding Amount
$482,962.00
Summary
This project investigates a crucial but neglected element in the mechanism of chronic pain that develops after nerve and tissue injury. In particular, our aim is to establish whether expression of a chemical target of the neurotransmitter noradrenaline increases in the painful skin of affected patients, and whether medication that blocks this target alleviates inflammation and pain. If so, this may open up new avenues for treatment for previously intractable pain syndromes.