Controlling rogue blood stem cells – Ashley Ng

Dr Ashley Ng seeing a patient. Credit: WEHI.

Dr Ashley Ng is revealing how blood stem cells are controlled, and how they sometime go rogue, leading to blood cancers. He has discovered how a protein known as ‘ERG’ underpins healthy development of blood cells, and how it also plays a role in Down syndrome-associated leukaemia and a range of other blood cancers.

As a researcher at WEHI and a clinician at the Royal Melbourne Hospital and Peter Mac, Ashley will use his $55,000 Metcalf Prize to advance his ideas from the laboratory into treatments for blood and blood cancer diseases.

Blood stem cells can form any cell of the blood system and they self-renew, so they are a source of endless supply. But, blood cancers can also arise from these cells, and are responsible for three per cent of all deaths in Australia. We need to understand why this occurs and use this knowledge to treat disease.

Winning a Metcalf Prize is personal for Ash. While studying for a Bachelor of Medical Science degree at the University of Melbourne, he had the opportunity to work in the late Professor Don Metcalf’s lab and became interested in blood cells and blood disorders.

“Throughout his career Don was always encouraging early career researchers. He was a great mentor and friend to me. So, I’m absolutely blown away by this award. It is very humbling, very emotional for me to receive this award.”

After gaining his BMedSci and his degree in medicine, Ashley did a further 10 years training to become a specialist haematologist. He is currently a consultant in haematology at the Royal Melbourne Hospital and the Peter McCallum Cancer Centre. But in 2008 he also returned to the lab, and a PhD at WEHI leading to postdoctoral work as clinician researcher in the areas of blood stem cells, immunology and leukaemia.

A focus of his work has been ERG, a transcription factor or protein that regulates gene activity in the cell nucleus. In fact, ERG works at the highest level of the regulatory hierarchy, controlling the activity of networks of other genes.

“ERG plays different roles in the development of different blood cell types. It is very important to what a blood cell becomes. It is absolutely required for the development of blood stem cells and critical to the development of the B cells, which are a major component of our immune system.” Imbalances in ERG can also lead to blood cancers and other blood disorders.

Ashley is now in a position to zero in on just how ERG has its impact. His proposed Metcalf Prize research project aims to do just that. With the help of colleagues at WEHI he has developed tags that bind to ERG and will allow him to track where the molecule goes, with what other molecules it interacts, and the stem cell genes it controls.

It will also provide a molecular map of gene regulatory networks in blood stem and progenitor cells that will serve as a resource for researchers in the field. Being a clinician as well as a researcher helps define the questions he wants to ask in the laboratory, Ashley says. “All human disease has some sort of molecular basis. So, to understand and develop new treatments for disease, we need to know how it develops at a molecular level to identify the key players to control. While investigating molecular mechanisms may appear far from the clinic, we are living in an era of molecular medicine, where translating relevant findings to patients can proceed at an incredible pace.”

Photos for media use