Associate Professor Andrew Murphy


Baker Heart and Diabetes Institute

2018 CSL Centenary Fellow

What really causes our arteries to clog?

We've long known the lifestyle risk factors for heart attack and stroke. But Andrew Murphy wants to know what is happening at a cellular level. What’s happening in our bone marrow that causes excess white blood cell production and leads to the clogging of our arteries?

Cracking this mystery could lead to a new generation of drugs to fight cardiovascular disease and contribute to new blood cancer treatments.

In 2011 Andrew discovered that an increase in white blood cells accelerates the development of artery-blocking plaque. Now, with the help of his $1.25 million CSL Fellowship, he’s planning to find out what is happening in the bone marrow where these cells are made.

"We know that high blood pressure, high cholesterol, lack of exercise, and smoking are all risk factors that contribute to heart attack and stroke. We know they contribute to the formation of artery-blocking plaques," Andrew says.

"Plaques form when cholesterol accumulates in the artery wall. White blood cells are summoned to remove the cholesterol. Sometimes this inflammatory response gets out of control, causing an increase in plaque and over-production of white blood cells."

But what are the fundamental processes at work, and how do they go wrong? Andrew has shown that we need to look in the bone marrow, where blood stem cells make white blood cells. Why, in cardiovascular disease, do these stem cells produce too many white blood cells? And why do they sometimes leave home, and spread to the spleen?

Andrew investigated the anti-inflammatory actions of lipoproteins for his PhD, before heading to New York and a postdoctoral fellowship at Columbia University. A series of discoveries of the role of cholesterol in inflammation led to a 2011 paper which reported that increased production of blood stem cells and white blood cells in the bone marrow accelerates the development of plaque.

The first project Andrew will undertake as part of his CSL Fellowship will investigate how diabetes and obesity alter bone marrow and its production of blood stem cells, and how that may accelerate atherosclerosis and cardiovascular disease.

His second project will explore how salt promotes cardiovascular disease. His team has already shown that a high salt diet encourages blood stem cells to spread to the spleen and produce more white blood cells there.

His third project will explore how to deliberately promote the development of blood stem cells for transplantation for cancer treatments.

Andrew is a National Heart Foundation Future Leader Fellow and a National Health and Medical Research Council Career Development Fellow. His research is supported by project grants from the National Health and Medical Research Council.

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