Congratulations to our members who were successful in their HRC Grant applications this year. The five successful members received a total of almost $6 million. You can read the details of their projects below.
Professor Julia Horsfield
Fighting leukaemia colonisation of the haematopoietic niche
Acute myeloid leukaemia (AML) has a low survival rate of 22 per cent in New Zealand. Treatment options for AML are limited and new strategies are needed to combat this disease. Understanding the function of AML-associated gene mutations is required to develop new therapies. Mutations in genes of the cohesin complex are present in ~12-20% of AML. Leukaemia stem cells can survive and evade treatment through interaction with the surrounding microenvironment known as the ‘niche’. We found that cohesin mutation enhances adhesive characteristics of leukaemia cells. We propose that these characteristics could promote increased interaction and colonisation of the leukemic cells into the niche. Zebrafish are an excellent model to study leukaemia development in vivo. This project will utilise cohesin mutant zebrafish models to examine the interaction and invasion potential of cohesin mutant cells within the niche, and determine whether niche interactions can be targeted for therapeutics.
Dr Euan Rodger
Identifying epigenetic markers for early detection of colorectal cancer
Colorectal cancer (CRC) death rates are particularly high in Aotearoa New Zealand and are increasing in younger people (age <50 years) and Māori, who are more likely to present with advanced stages of disease. Prognosis and survival of CRC patients rely heavily on the stage at diagnosis. Therefore, there is an urgent need for accessible and easily clinically-deployable biomarkers that enable early diagnosis and improve CRC outcome. Recent work demonstrates that DNA methylation patterns could be used as a powerful tool for highly specific and highly sensitive early tumour detection. We aim to use unbiased whole genome-scale analysis to identify DNA methylation markers in the blood that can be used for minimally invasive early detection of CRC patients. In the future, our work will contribute further to enhanced surveillance for relapse and treatment response to improve CRC outcomes in New Zealand.
Dr Rachel Purcell
Targeting the tumour microenvironment to improve outcomes in rectal cancer
The incidence of rectal cancer is increasing in NZ, particularly in younger people (< 50 years). Radiotherapy is often used to treat rectal cancer but patients have varying response, and currently, there are no predictive biomarkers of response available. Our recent work has identified an immune signature in rectal tumours that is predictive of response to radiotherapy, and, based on this, we will validate a biomarker test in an international cohort to predict response to radiotherapy and better direct treatment for rectal cancer patients. In addition, we found that the immune signature is linked to a specific tumour microbiome. We will use state-of the art techniques to determine the tumour immune-cell microenvironment that co-operates with radiotherapy and explore the potential of microbiome-based interventions to improve response to radiotherapy. This work will lead to the development of novel tests and microbiome-based treatments for rectal cancer, and ultimately improve outcomes for cancer.
Dr Htin Aung
Understanding inequitable tuberculosis transmission in Aotearoa
In Aotearoa New Zealand tuberculosis (TB) disproportionally affects Māori and Pasifika particularly children under five and 5-14 years, suggesting ongoing transmission is occurring in these communities. Adding to this problem, there are variants of TB-causing Mycobacterium tuberculosis bacteria which predominate in these communities. Our research project will investigate TB transmission in Māori and Pasifika communities, by combining the expertise of bacterial genetics, epidemiology, and social science research teams. This will involve working alongside communities and combining expertise from public hospitals, New Zealand universities and Te Whatu Ora in a collaborative approach. Utilising this culturally-responsive, transdisciplinary approach, our research project also aims to serve as a blueprint to tackle other infectious diseases in New Zealand and promote better health outcomes for New Zealanders.
Professor Merilyn Hibma
A molecular triage test to reduce colposcopy referrals after HPV testing
In 2023, the primary test for cervical screening will change to human papillomavirus (HPV) testing. HPV testing can be carried out on a self-collected swab, improving accessibility of screening for Māori and other women. However, a follow-up invasive triage test may be required. Additionally, many women referred to colposcopy following an HPV+ test do not have disease and would be better managed with monitoring. The purpose of this research is to develop a triage test for HPV+ women using the cells from a self-collected vaginal swab that will distinguish high-grade disease requiring treatment from low-grade disease that can be monitored. RNA sequencing will be used to identify disease-associated changes in gene expression and an assay will be developed and evaluated for its diagnostic effectiveness in a cross-section of HPV+ women. If successful, this test will have a significant impact on women’s health and on health delivery nationally and globally.
