New funding for Centenary's life saving research

The Centenary Institute has welcomed the Federal Government’s announcement of funding for 9 new and innovative medical research projects via the latest round of NHMRC grant rounds funding, officially confirmed today.

The successful grants cover a diverse range of research areas and diseases, including chronic skin inflammation, liver cancer, liver disease, genetic heart conditions, tuberculosis, type 2 diabetes, rheumatoid arthritis and lupus erythematosus.

The Centenary Institute’s Executive Director, Professor Mathew Vadas AO, has welcomed this support from the Federal Government.

“This vital funding support will help ensure Centenary stays at the forefront of cutting edge medical research, delivering the critical breakthroughs needed to understand disease and find cures,”Professor Vadas said.

“The Centenary Institute relies on the generous support of the Australian and NSW Governments, as well as the wider Australian community to fund our life saving research in the areas of cancer, inflammation and cardiovascular disease.

“Every day we come closer to delivering new drugs, treatments and cures to some of the most chronic diseases affecting today’s society. Every dollar invested in medical research is an investment in the future health and wellbeing of all of us.”

2015 NHMRC grants received by the Centenary Institute cover the following projects:

Mast cell precursors and skin disease

Mast cells (MC) are key regulators of chronic skin inflammation, such as atopic eczema, and can also give rise to a group of diseases called mastocytosis. How MC numbers are regulated in these conditions is poorly understood. We have identified a novel circulating precursor cell that gives rise to MC. We will determine the function of these precursors in skin diseases, including eczema and mastocytosis, with the aim to curtail the course of these difficult-to-treat conditions.

A novel liver cancer therapy targeting tumour stroma

In Australia, there are 1,300 new cases of liver cancer each year with an average survival of 7 months. Liver cancer is now the most rapidly increasing cancer, probably caused by more hepatitis, obesity and diabetes. Our commercial partner has a novel innovative new antibody that shrinks other cancer types and we want to see how well it combats liver cancer in mice. This antibody has a raft of superior features and we have a clear plan towards making it available to patients.

Genetic Basis of Childhood Cardiomyopathy

Cardiomyopathies (heart muscle problems) are the most common inherited heart conditions and represent an important clinical problem. The clinical and psychosocial impact on both the children and their families is significant. The proposed research will improve our understanding of the clinical and genetic basis of childhood cardiomyopathies, and how genetic factors may influence the development, progression, and clinical outcome, including heart failure, transplantation, and sudden death.

Inhibition of haemostasis as a novel host directed therapy for tuberculosis

Mycobacterium tuberculosis induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish and out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.

The role of the actomyosin cytoskeleton in T cell-mediated anti-tumour immunity

T cells, specialised immune cells, are crucial in the defence against tumours. In order to reach cancerous target cells, T cells must enter tumour tissues from the blood stream and then effectively migrate in the extravascular space. This application aims to uncover the role of the cytoskeleton, a group of molecules driving cell shape change and motility, in the efficient execution of T cell anti-tumour function. These studies will aid the development of improved immunotherapies against cancer.

DPP4 family proteases as drivers of chronic liver injury

Type 2 diabetes afflicts over 220 million people and often causes a chronic liver injury. That and hepatitis viruses can cause cirrhosis, liver failure and liver cancer, which is the 2nd most common cause of cancer death. Many Australians suffer from diabetes, fatty liver and/or hepatitis virus infection. We will understand these diseases far better and likely discover a new therapy by assessing roles of the DPP4 family of enzymes in diabetes, fibrosis and fatty liver.

Dynamics and mechanisms of immune complex-mediated skin inflammation

Type III hypersensitivity underlies a number of common autoimmune diseases, including rheumatoid arthritis and lupus erythematosus. These diseases are caused by the deposition of immune complexes (IC) and the accumulation of neutrophils within small blood vessels. We will use real time imaging to dissect in space and time the recruitment of neutrophils and IC deposition during type III hypersensitivity reactions in order to better understand the pathogenesis of these conditions.

A unique network of phagocytic cells at the interface between the liver and peritoneal cavity

This project aims to characterise the nature and ontogeny of a novel population of cells with phagocytic capacity that forms a network underlying the capsule of mouse and human liver reminiscent of that formed by Langherans cells in the epidermis of the skin. In this project we will characterise this newly described liver capsular macrophage subset, define their ontogeny and assess their specific functions.

Role of sphingolipid signalling in hepatic insulin resistance and its application in prediction of risk for type 2 diabetes and prediabetes

There has been a striking increase in the prevalence of both type 2 diabetes mellitus (T2D) and prediabetes worldwide. Prediabetes is usually unrecognized and constitutes a major public health concern that needs earlier interventions, because the majority of prediabetic subjects proceed to T2D. On the other hand, in the prediabetic stage, lifestyle modifications and some medications can ameliorate insulin resistance and hence delay or reduce the progression to T2D. Thus, there is an urgent need to identify high-risk populations of prediabetes by using a biomarker. This project will not only elucidate a new mechanistic cause of hepatic insulin resistance, but also provide a potential biomarker that identify high-risk populations with prediabetes and/or diabetes, which will help the management of obesity, T2D and other relevant diseases at both public health and clinical levels. For further information about the Centenary Institute visit www.centenary.org.au

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