Funded Research

Over the past two years, Genomics Into Medicine has helped support the research of 58 researchers/clinicians/geneticists across 12 research projects:

2018/2019 GIM funded projects

Nikki Earle – University of Auckland
Stefan Bohlander – University of Auckland
Peter Browett – University of Auckland
Malcolm Legget – University of Auckland
Rob Doughty – University of Auckland
Katrina Poppe – University of Auckland
Purvi Kakadiya – University of Auckland

Coronary artery disease is one of the leading causes of death in New Zealand. An important goal is to accurately identify high-risk individuals and offer preventive interventions. Nikki Earle and colleagues will sequence a panel of 70 myeloid genes from individuals participating in a subclinical atherosclerosis study. This will enable the team to assess whether clonal haematopoiesis of indeterminate potential (CHIP) is a risk factor for atherosclerotic cardiovascular disease and whether this myeloid gene panel can be used to eventually increase the accuracy of cardiovascular risk assessment.

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Kimiora Henare – University of Auckland
Maui Hudson – University of Waikato

Understanding the challenges and barriers to indigenous participation in genomic research is a pressing concern, given the pace of this research area and the significant inequities in health outcomes for Māori and Pacific people in New Zealand. Māori leadership and focus is needed to establish an indigenous-led education platform for researchers, clinicians, counsellors, educators, and community members with an active stake in genomics-based medicine. Kimiora Henare and Maui Hudson will develop a discussion document on ‘The Challenges of Enhancing Indigenous Participation in Genomic Medicine’, laying the foundation for an Indigenous Genomics Conference to be held in Aotearoa in 2020.

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Polona Le Quesne Stabej – University of Auckland
Patrick Yap – Genetic Health Service NZ, Auckland District Health Board
Cristin Print – University of Auckland
Ben Curran – University of Auckland
Peter Tsai – University of Auckland
Mark Greenslade – LabPLUS, Auckland District Health Board
Phil Asquith – LabPLUS, Auckland District Health Board
Tarn Donald – LabPLUS, Auckland District Health Board
Audrey Long – Auckland District Health Board
Monique Stein de Laat – Auckland District Health Board
Mariam Buksh – Auckland District Health Board
Ian Hayes – Genetic Health Service NZ, Auckland District Health Board
Juliet Taylor – Genetic Health Service NZ, Auckland District Health Board
Nerine Gregersen – Genetic Health Service NZ, Auckland District Health Board
Raoul Heller – Genetic Health Service NZ, Auckland District Health Board
Kimberley Gamet – Genetic Health Service NZ, Auckland District Health Board

Non-immune hydrops foetalis (NIHF) is a condition characterized by an abnormal accumulation of fluid in at least two different foetal organ spaces and has a perinatal mortality rate estimated to be >50%. Although the majority of cases likely have a genetic cause, only a subset can be explained by standard genetic tests. Le Quesne Stabej, Yap and colleagues will use trio whole-exome sequencing of parents and their neonates affected by NIHF. This study will contribute towards a better understanding of pathomechanisms of NIHF through delineation of its genetic causes. In the longer term, this will enable accurate clinical diagnosis and prognosis, reproductive risk clarification and medical management of the condition.

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Soizick Mesnage – University of Auckland, Auckland District Health Board
Michelle Wilson – University of Auckland, Auckland District Health Board
Cristin Print – University of Auckland
Andrew Shelling – University of Auckland
Cherie Blenkiron – University of Auckland
Kathryn Payne – Auckland District Health Board
Katrina Sharples – Cancer Trials New Zealand
Kimberley Gamet – Genetic Health Service NZ, Auckland District Health Board

Gynaecological cancers, such as ovarian, endometrial or cervical cancer, are a major cause of morbidity and mortality. Soizick Mesnage and team will evaluate cancer- and immune-related gene expression in gynaecological malignancies, and the evolution of gene expression from diagnosis to relapse, to gain insights into mechanisms of tumour proliferation, resistance and the anti-tumour immune response. The study will integrate this information with genomic DNA sequence data to provide a deeper understanding of the link between functionally significant genomic alterations that drive tumourigenesis, resistance and the anti-tumour immune response.

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Richard Roxburgh – University of Auckland, Auckland District Health Board
Gina O’Grady – Auckland District Health Board
Miriam Rodrigues – Auckland District Health Board
Christina Buchanan – University of Auckland

Many families in New Zealand dealing with neuromuscular or other neurogenetic diseases do not have a genetic diagnosis. Richard Roxburgh and team will conduct a pilot project to establish pathways and infrastructure to enable whole exome sequencing for patients with neurogenetic disease. Patients not receiving a diagnosis through clinical gene panels of well-known mutations will be considered for inclusion in an ongoing collaborative study with international colleagues to identify neurogenetic disease-causing genes. The framework established through this project will lead to the development of a well-established in-house neurogenetic research Exome/Genome pipeline in Auckland.

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Emma Scotter – University of Auckland
Richard Roxburgh – University of Auckland, Auckland District Health Board
Christopher Shaw – King’s College, London
Mike Dragunow – University of Auckland

New Zealand’s rate of motor neuron disease (MND) is among the highest in the world and may be partially underpinned by genetics. Emma Scotter and colleagues will develop a diagnostic pipeline for familial MND cases that will decrease the cost of providing diagnostic coverage of all known causative, risk factor and modifier genes. Those patients that do not receive a genetic diagnosis for their MND using this pipeline will be candidates for whole exome sequencing as part of an international gene-hunting effort. A number of gene-specific therapies for MND are on the horizon and a better understanding of the relevant DNA variants in the New Zealand population will help connect people with MND to appropriate therapies.

 

2017/2018 GIM funded projects

Susan Bigby – University of Auckland
Andrew Shelling – University of Auckland
Anita Muthukaruppan – University of Auckland
Lois Eva – Auckland District Health Board
Peter Tsai – University of Auckland
Nicholas Knowlton – University of Auckland

Squamous cell carcinoma of the vulva (SCCV) is rare but potentially debilitating, with relapse more common in cases that arise independently of human papillomavirus (HPV) involvement. A clinically important question is whether relapses represent spread of the original cancer, or new cancers arising in damaged skin predisposed to cancer development. Susan Bigby and team will use Next Generation Sequencing (NGS) to explore the relationship between primary and secondary vulval cancers, testing the hypothesis that early somatic mutations predisposing women to SCCV can be detected in the background skin, and that relapses are comprised of both true relapses and new tumours.

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Francis Hunter – University of Auckland
Stephen Jamieson – Auckland Cancer Society Research Centre, University of Auckland
Cristin Print – University of Auckland
Peter Shepherd – University of Auckland
Rosalie Stephens – Auckland City Hospital
Stefan Bohlander – University of Auckland
Bill Wilson – Auckland Cancer Society Research Centre, University of Auckland

New Zealand has the highest rate of melanoma in the world. Of particular concern are the 15-20% of aggressive melanomas that harbour mutations in the NRAS gene, for which no effective drugs are available after immunotherapy fails. One promising approach to cancer therapy is to identify and target proteins that are essential to the survival of neoplastic cells that harbour a specific mutation. Stephen Jamieson and colleagues will use next-generation DNA sequencing and whole-genome CRISPR-mediated gene knockout screens to survey the entire complement of human genes and identify those that are essential to the survival of NRAS melanoma cells.

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Stephen Jamieson – Auckland Cancer Society Research Centre, University of Auckland
Andrew Macann – Auckland District Health Board
Nick McIvor – Auckland District Health Board
John Chaplin – Auckland District Health Board
Dennis Kee – LabPLUS, Auckland District Health Board
Tet-Woo Lee – Auckland Cancer Society Research Centre
Phillip Shepherd – Auckland Regional Tissue Bank, University of Auckland
Bill Wilson – Auckland Cancer Society Research Centre, University of Auckland
Cristin Print – University of Auckland
Stefan Bohlander – University of Auckland

Stephen Jamieson and colleagues have developed new tumour models of head and neck cancer squamous cell carcinoma (HNSCC) using patient-derived xenografts (PDXs), in which patient tumour specimens are engrafted directly into highly immunodeficient mice. Their study will evaluate the clinical validity of these PDX models of HNSCC using comprehensive RNA sequencing (RNAseq) to assess the expression profile of every gene in these tumour cells compared to clinical tumours and standard xenograft models. The tumours that most closely recapitulate the human gene expression profile of the clinical tumours will be used for preclinical testing of their novel hypoxia-activated prodrugs.

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Erin Macaulay – Genetic Health Service NZ, Auckland District Health Board
Kimberley Gamet – Genetic Health Service NZ, Auckland District Health Board
Helen Wihongi – Auckland District Health Board
Kim Southey – University of Waikato
Cristin Print – University of Auckland

Erin Macaulay and colleagues will explore the possibility of developing national genomic consent documents for clinical genetics performed in conjunction with research. Genetic counsellors and clinical geneticists will be surveyed to identify the clinical information that should be included in the consenting documents and how media/online tools may be utilised. Draft documents/tools will be assessed by Māori and Pacifica liaisons to ensure they meet the cultural needs of their people. This project will reduce inconstancies in the information a patient/participant receives between services/groups and improve the cultural appropriateness of genomic consenting documents.
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Kelly Sullivan – Auckland District Health Board
Romy Kerr – Auckland District Health Board
Cherie Blenkiron – University of Auckland

The cost and time required to sequence genetic information has exponentially decreased, such that genomic sequencing of tumours is now realistically part of clinical medicine. Oncologists must now be able to interpret the relative contributions of germline and somatic mutations to tumour development. However, medical education has not kept pace with this disruptive technology and few specialists outside genetics receive formal training in genomics. Kelly Sullivan and team will conduct qualitative semi-structured interviews with oncologists from various sub-specialties working in Auckland. Thematic analysis will be used to develop an understanding of oncologists’ perceptions of genomics and to establish their educational needs.

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Patrick Yap – Genetic Health Service NZ, Auckland District Health Board
Stefan Bohlander – University of Auckland
Purvi Kakadiya – University of Auckland

Whole exome sequencing (WES) is widely used in clinical and research settings to diagnose rare monogenic genetic disorders. However, even after detailed clinical phenotyping of patients, and WES or comprehensive gene panel analysis, 40-70% of patients remain undiagnosed. Patrick Yap, with clinical and research colleagues within the Auckland District Health Board and University of Auckland, will perform trio WES in this group of patients with proposed ultra-rare and/or unique phenotypes of unknown molecular origin. This study will enhance diagnostic rate and gene discovery and help develop clinical grade trio WES for patients in New Zealand.