2015 PAHMR recipients
The Recipient of the 2015 Premier’s Award for Health & Medical Research
Dr Peter De Cruz - The University of Melbourne
Crohn’s disease is a chronic bowel condition that is on the rise internationally. Eighty per cent of patients with Crohn’s disease need an operation at some time in their life. Unfortunately even if the entire diseased intestine is removed, the disease nearly always recurs, and 70% of those who have had an operation will require more surgery.
Dr Peter De Cruz together with Professor Michael Kamm from the University of Melbourne, initiated and coordinated an international study of 174 patients with Crohn’s disease to trial a more proactive approach to post-operative care. Rather than waiting until symptoms return, a colonoscopy was performed early in the postoperative period to look for signs of change to the patient’s bowel. If early changes were detected during the colonoscopy, medication was prescribed to help prevent tissue damage.
The results of this study have been outstanding and were published in The Lancet in 2014. The study found that participating patients experienced significantly fewer recurrences and required fewer surgeries than would otherwise have been required. The results have changed practice internationally.
Alongside this landmark study, Dr De Cruz also explored the role that both good and bad gut bacteria may play in causing Crohn’s disease, and the way that they may influence its severity and recurrence. Dr De Cruz’s findings have significantly advanced the field and have been instrumental in the development of therapies targeted at specific gut bacteria that may help to treat Crohn’s disease.
Commendations were awarded to
In no particular order:
Dr Lucille Rankin - The Walter and Eliza Hall Institute of Medical Research
A family of immune cells in our bodies called innate lymphoid cells (ILCs) are critical for protective immunity and good intestinal health. Abnormalities in these cells can lead to the development of health problems of the intestine. Dr Lucille Rankin’s doctoral research at the Walter and Eliza Hall Institute of Medical Research has shown that a particular gene (T-bet) is essential for the generation of a specialized population of ILCs. This is because T-bet is a critical part of the complex signalling pathway that works to generate these cells.
Dr Rankin then used a sophisticated genetic mouse model to determine the role of this ILC population during intestinal infection. Dr Rankin also collaborated with Dr Cyril Seillet to identify another gene that is important for the generation of all different types of ILCs. This gene is called Nfil3 and its absence makes mice extremely susceptible to intestinal infections.
By finding the molecular switches responsible for generating ILCs, Dr Rankin’s research has provided valuable new insights into how we might target these cells in diseases such as irritable bowel syndrome.
Dr Daniel Pellicci - The University of Melbourne
The immune system encompasses a complex collection of cells that act together to protect us from disease. T cells are a major subset of immune cells and are essential for survival. Most studies of T cells to date have focussed on those that respond to protein fragments (peptides) from viruses, bacteria and other pathogens.
Dr Daniel Pellicci from the University of Melbourne has undertaken research with a focus on another specialised population of T cells, called Natural Killer T cells. These cells respond to lipids or fat molecules rather than peptides. Despite their importance and the unique role they have in infection, cancer, allergy and autoimmune disease, there is a serious lack of understanding of how Natural Killer T cells specifically recognise different kinds of lipids and therefore influence different immune responses.
The aim of Dr Pellicci’s PhD was to investigate how Natural Killer T cells recognise foreign lipids like those from bacteria, and the self-lipids from human cells. His studies revealed that Natural Killer T cells from mice and humans recognise lipids in a similar manner by ‘moulding’ selflipids to resemble foreign lipids.
This work has provided critical knowledge into how Natural Killer T cells participate in infectious and non-infectious diseases. Accordingly, Dr Pellicci’s research provides fundamental insight into the biology of Natural Killer T cells and their importance in the immune system, which will have an impact on a range of diseases.
Mr James Rickard - The Walter and Eliza Hall Institute of Medical Research
Inflammatory diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel disease cause significant human suffering. By inhibiting Tumour Necrosis Factor (TNF), a protein that switches on inflammatory genes, treatment of these diseases has been revolutionised. But not all patients respond to this treatment.
During his PhD research, Mr James Rickard and colleagues from the Walter and Eliza Hall Institute of Medical Research characterised two proteins, including one called RIPK1, that regulate TNF and established that their absence causes cell death, leading to inflammation. TNF induced cell death caused widespread disease, including psoriasis-like skin disease and intestinal inflammation. This showed an alternate mechanism by which TNF can cause damage.
Some disease also arose independently of TNF, suggesting that in certain scenarios inhibiting cell death might reduce inflammation more potently than current treatments like TNF inhibitors. Some cell death involved ‘necroptosis’, which is like a cellular explosion with leakage of intracellular contents into tissue that incites inflammation. RIPK1 activates necroptosis and has been therapeutically targeted in pre-clinical trials successfully. Mr Rickard’s research showed that RIPK1 also inhibits necroptosis in some tissue types, indicating a protective function for RIPK1 that must be preserved when therapeutically targeting it. This research has given significant insight into the therapeutic potential of inhibiting cell death in inflammatory disease.