Gamble
Blood vessels supply every organ in our body with oxygen and nutrients, and are essential for the removal of toxic compounds from organs. Further, the cells that comprise the blood vessels are major control points for the regulation of the timing, extent and type of inflammation. We are particularly interested in the endothelial cells, cells that form the inner lining of the vessels, and their interacting partners, the pericyte or smooth muscle cells and the perivascular macrophages.
Our major effort is to understand the ageing process in these cells, since age is the biggest risk factor for disease and chronic disease is generally associated with blood vessel dysfunction. We are particularly focused on Alzheimer’s Disease and heart disease-two significant diseases of the aged, where both have a major vascular component and where the incidence of these diseases is increasing in the population.
The program has 3 main areas under investigation:
- Endothelial cell ageing: Endothelial cells form the lining of blood vessels and they maintain the anti-inflammatory, anti-thrombotic and selectively permeable nature of blood vessels. Cardiovascular diseases, which are linked to age, all show endothelial cell dysfunction. We are investigating the molecular, biological and metabolic changes that are induced in ageing endothelial cells and how these changes could predispose us to diseases of the age.
- Alzheimer’s disease (AD): AD is an age-related neurodegenerative disease that progressively affects brain function. AD is the most common form of dementia, which is the 2nd leading cause of death in Australia. In 2019 there were approximately 500,000 Australians with dementia, of which about 70% suffer from AD. One of the new concepts in AD is that changes in the brain vasculature are an early major contributing factor to the pathogenesis. The significant change seen early in AD is in the breakdown in the blood-brain barrier, where the vessels become leaky and this occurs before the formation of the classic features of Alzheimer’s pathology, the plaques and the tau tangles. Our research is directed to understanding the molecular changes that occur in the blood vessels that result in vascular leak and the progression of Alzheimer’s pathologies.
- Calcific aortic valve disease (CAVD): CAVD is an age-related cardiovascular disease, and the most common valvular heart disease in developed countries, affecting 2-4% of those over 65 years. CAVD begins as mild sclerosis of the valve and progresses to stenosis and calcification, with increased stiffness and fusion of the leaflets. Interventions, such as aortic valve replacement or less invasive transcatheter aortic valve replacement technologies are costly, are often delayed until the late stages of the disease when left ventricular dysfunction has occurred. At present there are no drug therapies available, and few in development, largely due to the limited understanding of the underlying molecular and cellular mechanisms driving calcification. Our focus is elucidating the effect of age on the function of the cells of the valve leaflets and the process of calcification.
Australian
CTR Endothelium
Macquarie University
University of Queensland
University of Sydney
International
Fudan University, China
Ranger Biotechnologies A/S, Denmark
The program has 3 main areas under investigation:
- Endothelial cell ageing: Endothelial cells form the lining of blood vessels and they maintain the anti-inflammatory, anti-thrombotic and selectively permeable nature of blood vessels. Cardiovascular diseases, which are linked to age, all show endothelial cell dysfunction. We are investigating the molecular, biological and metabolic changes that are induced in ageing endothelial cells and how these changes could predispose us to diseases of the age.
- Alzheimer’s disease (AD): AD is an age-related neurodegenerative disease that progressively affects brain function. AD is the most common form of dementia, which is the 2nd leading cause of death in Australia. In 2019 there were approximately 500,000 Australians with dementia, of which about 70% suffer from AD. One of the new concepts in AD is that changes in the brain vasculature are an early major contributing factor to the pathogenesis. The significant change seen early in AD is in the breakdown in the blood-brain barrier, where the vessels become leaky and this occurs before the formation of the classic features of Alzheimer’s pathology, the plaques and the tau tangles. Our research is directed to understanding the molecular changes that occur in the blood vessels that result in vascular leak and the progression of Alzheimer’s pathologies.
- Calcific aortic valve disease (CAVD): CAVD is an age-related cardiovascular disease, and the most common valvular heart disease in developed countries, affecting 2-4% of those over 65 years. CAVD begins as mild sclerosis of the valve and progresses to stenosis and calcification, with increased stiffness and fusion of the leaflets. Interventions, such as aortic valve replacement or less invasive transcatheter aortic valve replacement technologies are costly, are often delayed until the late stages of the disease when left ventricular dysfunction has occurred. At present there are no drug therapies available, and few in development, largely due to the limited understanding of the underlying molecular and cellular mechanisms driving calcification. Our focus is elucidating the effect of age on the function of the cells of the valve leaflets and the process of calcification.
Australian
CTR Endothelium
Macquarie University
University of Queensland
University of Sydney
International
Fudan University, China
Ranger Biotechnologies A/S, Denmark
