Vascular Biology
Blood Vessels play a key role in keeping us healthy. But sometimes the growth of new blood vessels can exacerbate diseases such as cancer and heart disease.
Group Head: Professor Jenny Gamble
Professor Gamble completed her Masters Degree at the Walter and Eliza Hall Institute in Melbourne and her PhD in 1994 at the University of Adelaide. During this time she was the first to describe the capacity of endothelial cells to be regulated by inflammatory cytokines thus exposing the endothelium as a major regulator of disease. She was a Founding Scientist of the Hanson Centre for Cancer Research (now Hanson Institute) in Adelaide and established the Vascular Biology group within the Institute. In 2007, Prof Gamble relocated to the Centenary Institute and has established the Vascular Biology group focusing her research effort on understanding the genetic regulation, including microRNA control of endothelial cell function and on the impact of senescence (or “ageing”) in disease. She is currently a Medical Foundation Fellow, Department of Medicine, University of Sydney.
About our Vascular Biology Research
The principle cell of the blood vessel is the endothelial cell (EC), which in most vessels forms a continuous lining, regulating the passage of nutrients
and cells from the blood into the tissues. In adults, blood vessels normally do not proliferate except during the female reproductive cycle. However, in pathologies such as solid tumour growth and cardiovascular diseases, uncontrolled blood vessel growth and dysfunctional endothelial cells are a hallmark of these diseases.
The Vascular Biology Group is focused on understanding how mature endothelial cells form from their progenitor cells, the signals that operate to induce new blood vessel formation and ultimately what changes take place in the vessels upon ageing and in disease.
Research focus
Blood vessels age
One of the critical features of ageing is the increased incidence of cardiovascular disease and cancer. Indeed age is the most significant risk in cardiovascular disease development. We have discovered a gene SEN that causes endothelial cells to age undergoing a process known as senescence.
Expression of SEN1 is essential for EC survival, thus suggesting that SEN1 is a major fulcrum for dictating EC function. We have started a program of research to characterise how this gene is induced (for example, by oxidative stress), how it effects cellular functions (for example on vascular permeability) and the mechanism underlying its regulation.
Role of senescence in tumour growth
SEN1 is also expressed in epithelial cells and when over-expressed induces senescence similar to that seen in EC. However, SEN1 does not appear to be essential for epithelial cell survival and the mechanism of regulation displays differences to that seen for EC. Dr Matthew Grimshaw has initiated work to delineate the role of SEN1 in breast development and in breast cancer progression.
Blood vessel formation
Angiogenesis is a process of endothelial cell re-organisation and differentiation. miRNAs are endogenous non-coding RNAs which are expressed as
long hairpin-forming precursor RNAs that are further processed to 21-23 nucleotide RNA molecules. miRNAs regulate gene silencing generally by post-transcriptional mechanisms.
miRNAs are involved in developmental timing, apoptosis, metabolism and cell differentiation. Recently, abnormal patterns of miRNA expression have been found in disease states, including cancer. We have identified a group of miRNAs which are regulated during blood vessel formation and which control two different but major signalling pathways known to be essential for endothelial cell function.
Further work is directed to understanding the impact of these specific miRNAs in normal and tumour associated angiogenesis, particularly in progression from chronic liver cirrhosis to hepatocellular carcinomas.
Differentiation of Endothelial Progenitor Cells (EPC)
Since the maturation of EPCs to EC is a major differentiation process we predict that miRNAs will also serve central regulatory roles. We have initiated a project to identify the suite of miRNAs which control EPC differentiation and to determine whether these are common to the differentiation of EC from the three classes of EPC (bone marrow, peripheral blood and vascular wall).
