Awarded Project grants

Awarded Project Grants 2018

  • 26 Jun 2018

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June Round

Immunooncology of Merkel Cell Carcinomas ($25,000 – 6 Months) 1118005

Dr Cherie Blenkiron, Dr Kate Parker
Department of Molecular Medicine & Pathology, The University of Auckland

Merkel Cell Carcinoma (MCC) are a rare tumour that are often identified as small red, quickly growing lumps on the skin. As well as growing quickly they can also spread or metastasise to other sites in the body. MCCs are caused either by an infectious virus or more often here in New Zealand by genetic damage caused by sun exposure. These two environmental triggers themselves can be the downfall for the tumour, causing an immune response or white blood cell attack. The tumour can however overcome this attack through molecular camouflage. This is where new immunotherapies, like the Melanoma treatment Keytruda can be used to reawaken the immune cells. In order to understand whether people with MCC could benefit from immunotherapy, this study will identify the types of immune cells present in these tumours and decipher their molecular camouflage signals. The project will provide new biological information about an understudied rare cancer and in the long term it could support the provision of funded immunotherapy for people with MCC.

Whānau experience of a healthy homes initiative ($14,259 – 1 year) 1118001

Dr Kyle Eggleton
Department of General Practice & Primary Health Care, The University of Auckland

Cold damp houses are associated with poorer health outcomes. Significant evidence exists demonstrating that housing insulation may reduce exacerbations of asthma and respiratory illnesses. There are a number of healthy homes initiatives nationwide and this research intends to explore one such initiative, based in Northland, to ascertain whānau experiences of the programme. The research will determine the wider health benefits of insulating and warming damp homes and whether the implementation of the project has met whānau expectations. The intent of the research is to improve the delivery of healthy homes initiatives in order to align with whānau expectations.

CGRP and bone healing ($160,000 – 2 years) 1118008

Dr Brya Matthews, Dr Christopher Walker, Dr Dorit Naot
Department of Molecular Medicine & Pathology, The University of Auckland

Bone fractures cause severe morbidity in both young, active people, and in the elderly. Fracture healing is significantly delayed or fails to occur in approximately 10% of patients. Limited treatment options are available to treat poor fracture healing, so more insight is needed into the mechanisms involved in the healing process. Sensory nerves are abundant in bone tissue, more so following injury, however their function in the healing process is not understood. One of the neurotransmitters produced by these nerves is known as CGRP and has previously been shown to promote bone formation. We will try to understand the role of CGRP in bone healing using a mouse model that lacks CGRP, as well as performing cellular studies to understand the mechanisms by which CGRP promotes bone cell activity.

Characterising the role of cardiac neurons in heart rhythm ($154,539 – 1.5 years) 1118003

Associate Professor Johanna Montgomery, Dr Jesse Ashton, Dr Kirsten Finucane, Dr Martin Stiles, Professor Bruce Smaill, Professor Julian Paton
Department of Physiology, The University of Auckland

Abnormal heart rhythms, termed arrhythmias, are devastating disorders. The most common arrhythmia, atrial fibrillation (AF), significantly increases the risk of stroke, heart failure, and dementia. Treatment strategies are limited, and more precise therapies are essential. One treatment target is the neurons located on the heart. These neurons regulate heart rhythm, and they can trigger AF. However, how these neurons trigger AF is unknown, which limits our ability to precisely target them to increase treatment success. We have assembled a team of scientists and clinicians with expertise in neurophysiology, cardiac physiology, cardiology and cardiac surgery. This enables us to examine the properties of cardiac neurons in animal models and human tissue for the first time. We hypothesise that changes occur in these neurons, termed “plasticity”, driving abnormal neuron activity in AF. We will identify the changes in cardiac neuron function during normal heart rhythm versus AF, and whether these changes can be reversed to stop AF. We will also establish protocols to precisely record from human cardiac neurons collected during heart surgery. Our novel data sets will advance our understanding of cardiac neuron function during normal and abnormal heart rhythm, which is critical to develop more precise therapies to treat AF.

Benzenesulphonamides: A promising new class of immunosuppressants ($158,808 – 2 years) 1118004

Dr Julie Spicer, Dr Kate Gartlan, Dr Stephen Jamieson, Professor Geoff Hill
Auckland Cancer Society Research Centre, The University of Auckland

Stem cell transplantation is used to treat cancers such as leukaemia, lymphoma and myeloma, but in many cases the patient’s immune system sees the incoming cells as ‘foreign’ and they are rejected, often with fatal consequences. This is because without a perfectly-matched donor, the procedure relies on mis-matched grafts from stored umbilical cord blood or partly-matched grafts from relatives. The cells responsible for early rejection overwhelmingly use a protein called perforin to kill the transferred stem cells. We have developed a class of small molecules that can block this process in the critical period of 4-5 days after the transplant. This will allow far more stem cells to survive and migrate to the marrow where they will essentially be in a ‘safe haven’ and able to multiply to produce red blood cells, white blood cells and platelets. Effective perforin inhibitors would increase the number of successful stem cell transplants, improving survival from potentially fatal cancers and with applications in solid organ transplantation more generally. In this project we plan to optimise the potency, physicochemical and pharmacological characteristics of these molecules to give safe and efficacious candidates suitable for pre-clinical development.

Inflammation and Cochlear Implantation ($158,942 – 2 years) 1118002

Professor Peter Thorne, Associate Professor Phil Bird, Associate Professor Srdjan Vlajkovic, Dr Andrew Wise, Dr Ravindra Telang
Department of Physiology, The University of Auckland

Deafness is a leading cause of disability worldwide and affects over 18% of New Zealanders. It occurs predominately from injury or disease of the cochlea of the inner ear and the primary treatment is with hearing aids or cochlear implants. Cochlear implants, normally for people with total deafness, are now available for people with some residual hearing but in many cases the hearing can deteriorate following implantation, possibly due to inflammation from surgery. This research will investigate a novel approach to reduce the inflammation by applying an activator (or agonist) of the Adenosine receptors in the cochlea that have been shown to inhibit inflammation in other tissues. We will test this in an animal model by applying the drugs loaded into nanoparticles, which are inserted surgically along with the implant. Our preliminary findings show that these drugs can reduce the post-implant deterioration in hearing and in this study, we will confirm if this is due to inhibition of inflammation. If these studies are successful, it should be easily translatable to treating patients during implant surgery as the compounds are already approved for use in humans. Protecting the ear during surgery is important to maximise the outcome of the cochlear implant.

The role of Epac in diabetic heart disease ($155,688 – 2 years) 1118006

Dr Marie-Louise Ward, Dr Sarbjot Kaur, Mr Nicholas Kang, Professor Peter Ruygrok
Department of Physiology, The University of Auckland

Type 2 diabetes (T2D) is one of the largest and fastest growing health issues within New Zealand, and is closely linked with the development and progression of cardiovascular diseases, including cardiac dysfunction, arrhythmias and heart failure. Decades of research using experimental animal models of diabetes suggest that the development of diabetic heart disease is progressive, beginning soon after the onset of diabetes, and resulting in subcellular changes to the cardiomyocytes that impact upon their function. Recently, exchange proteins activated by cAMP (known as “Epac”) have been shown to induce alterations in intracellular calcium regulation when activated in many cell types, including heart muscle. Cyclical changes in intracellular calcium control contraction and relaxation of heart muscle, which enables it to function as a pump. Experimental activation of Epac in isolated heart cells upsets calcium cycling. This results in less calcium available for excitation-contraction coupling, and an increased susceptibility to developing arrhythmias. Incomplete relaxation between beats can also occur if calcium within the muscle cells remains high. Our study will investigate Epac in tiny human atrial tissue samples obtained from consenting patients undergoing routine surgery. We hypothesise that altered Epac activation and location in T2D promotes abnormal muscle cell calcium handling. We aim to test this by measuring the relative abundance and distribution of the Epac isoforms (1 & 2), as well as their function and ultrastructural organization in atrial tissue samples from non-diabetic and T2D patients. This study will provide new knowledge of human T2D and the cellular changes that are detrimental to the heart during diabetes.

Novel treatment for acute pancreatitis ($159,266 – 2 years) 1118007

Professor John Windsor, Dr Jiwon Hong
Department of Surgery, The University of Auckland

Acute pancreatitis is a common and potentially fatal disease for which there is no specific drug treatment. Our studies have provided a new treatment paradigm that is based on the concept that the gut becomes leaky during acute pancreatitis and that toxic factors are taken up by gut lymph and drained into the main blood circulation. These toxic factors cause severe inflammation and injury to vital organs such as the heart, lungs and kidneys, which in turn results in a worse clinical outcome. This project is the first to test two types of drugs which specifically target key factors in the gut-lymph responsible for it’s toxicity in acute pancreatitis. The first study is designed to show that these two drugs are taken up preferentially by gut lymph and as a result reduces the toxicity of the gut-lymph when tested on cultured cells. The second study is designed to show that one of the drugs is effecting in reducing inflammation and organ injury. These critical proof-of-principle studies will directly contribute to further drug development and to the design of larger clinical studies which are necessary to translate this new treatment strategy for acute pancreatitis.

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