HRI is delighted to announce the award of three grants funded by donors to support research into cardiovascular disease – the biggest killer in not just Australia and New Zealand, but the world.
The grants, which will ensure the advancement of critical heart research with collaborators based in New Zealand, were awarded to HRI’s Cardiovascular-protective Signalling and Drug Discovery Group, Clinical Research Group and Haematology Research Group.
Safter treatments for ischaemic stroke, Cardiovascular-protective Signalling and Drug Discovery Group
The Cardiovascular-protective Signalling and Drug Discovery Group, led by Dr Xuyu Liu, will be conducting a collaborative research project entitled “Photo-responsive thrombin inhibitors enable precise control of localised antithrombotic therapy” with the Ferrier Research Institute of the Victoria University of Wellington (VUW), New Zealand.
Stroke is a leading cause of death and disability in New Zealand and globally, but there is currently only one approved drug treatment for stroke, called rTPA. Previous studies have revealed that anticoagulants can substantially improve the efficiency of rTPA, but they pose a high risk of life-threatening bleeding. This bleeding consequence is ascribed to the indiscriminate inhibition of all roles of thrombin in our circulatory system, the key enzyme in blood clotting, thrombosis and stroke.
Dr Liu’s research will address this shortfall by investigating the transformation of a direct thrombin inhibitor into a photo-responsive therapy for stroke, with the aim to precisely control local anticoagulation using two-photon excitation lasers. It will also provide proof-of-concept information on the utility of this photo-pharmacology system in the treatment of thrombosis and stroke for the first time.
The computational modelling and drug screening in this project will be conducted by Dr Wanting Jiao, who is based at the Ferrier Research Institute of VUW. The project will also involve collaboration with Dr Kai Chen, who will employ world-class spectroscopy techniques and laser facilities for the development of photo-anticoagulant therapy at the Robinson Research Institute of VUW. This collaborative research team aims to develop a cutting-edge, much needed technological platform to create light-controllable drug molecules enabling rapid, non-invasive treatment of stroke. They are also combining the PROteolysis TArgeting Chimera discovery platform established at the Heart Research Institute with femtosecond laser technology to accelerate the development and screening of next generation PROTAC molecules specific for stroke and thrombosis.
“This project has the potential to develop safer treatment strategies for ischaemic stroke,” says Dr Liu.
“It also has the capacity to inspire new drug discovery strategies for cardiovascular disease more broadly.”
L-R: Prof David Celermajer and Dr Freda Passam. Dr Xuyu Liu in header image.
Improving patient care for congenital heart disease patients, Clinical Research Group
The Clinical Research Group, led by Professor David Celermajer, will be conducting a collaborative research project in New Zealand entitled “Congenital Heart Alliance of Australia and New Zealand (CHAANZ) Congenital Heart Disease Registry; Initiating the New Zealand CHD Registry”. The project will be run in conjunction with Auckland City Hospital, Starship Children’s Hospital Auckland, New Zealand.
Prof Celermajer chairs the Congenital Heart Alliance of Australia and New Zealand (CHAANZ), a consortium of paediatric, adult and surgical congenital heart disease (CHD) researchers from around Australia and the national CHD unit in Auckland, New Zealand. An earlier feasibility study conducted by Prof Celermajer found that there was an overall lack of understanding of CHD outcomes and burden in Australia and New Zealand. The study established the need for a collective CHD registry across Australia and New Zealand, to improve research and clinical outcomes. This would allow for improved understanding of the total numbers of patients living with CHD and the total burden across the life continuum, which is imperative for patients, those responsible for treating them and health care systems. The Australian CHD Registry has previously been funded by the Federal Government’s Medical Research Future Fund scheme.
In this research project, the Group aims to establish a comprehensive NZ registry of demographic and clinical data from cohorts of paediatric and adult cases of CHD from sites across New Zealand, with the goal of generating specific information about critical outcomes in people with CHD and the parents of children with CHD, including psychological, mental health, neurocognitive and quality of life. While accrual of data has already begun in Australia, the HRI grant will enable the initiation of data accrual from New Zealand.
“This project will generate the knowledge needed to better understand the true diversity of outcome and burden of the entire spectrum of CHD across the lifespan, in New Zealand as well as Australia, in a strong trans-Tasman collaboration,” says Prof Celermajer.
“This data has the strong potential to improve patient care in both countries and to drive policy development towards optimal management of CHD patients.”
Researching preventative therapies for cardiovascular disease, Haematology Research Group
The Haematology Research Group, led by Dr Freda Passam, will be conducting the project “Role of ER stress in platelet function” in collaboration with the University of Auckland (UoA), New Zealand.
Platelets are critical for the development of cardiovascular complications in a wide range of diseases. Endoplasmic reticulum (ER) is a metabolic compartment of protein folding, calcium storage and lipid synthesis, but the downstream effects of ER stress in anucleate cells such as platelets is not well known.
This collaboration between Dr Passam and Dr Maggie Kalev-Zylinska, group leader in the Department of Molecular Medicine and Pathology, UoA proposes that platelet ER stress can lead to enhanced platelet secretion, a novel concept that may yield important mechanistic insights into platelet production and function. Increased platelet secretion is a feature of type 2 diabetes, which is a major risk factor for cardiovascular disease, and is linked to an increased tendency for blood clots in people with diabetes.
With a current paucity of research in this area, this project will generate significant new knowledge, with the potential to manipulate ER stress responses to prevent complications from blood clots in patients.
“This will be the first comprehensive study of platelet ER stress in health and cardiovascular disease, and could open new pathways for preventative therapies,” says Dr Passam.
