|Baylor College of Medicine, Houston, Tx, USA||1|
Validation of a novel DNA sequencing method ‘REAMS’ using DNA from Multiple Myeloma patients and Acute Myeloid Leukaemia mouse models, by developing bioinformatics protocols to enable comprehensive genetic and cytogenetic analysis of whole-genome sequencing data.
Investigating genomes (DNA/genes in cells) is complicated and expensive because multiple methodologies and laborious analysis are required, so detail is often sacrificed for simplicity. We aim to validate a novel technology, ‘REAMS’, that can study whole genomes in one method, substantially reducing time, complexity and cost whilst producing more detailed analysis than previously possible. We will study blood cancers: Multiple Myeloma (MM) and Acute Myeloid Leukaemias (AML). This may elucidate causes of MM/AML, mechanisms of MM/AML development, and new therapeutic targets, likely facilitating improvements in diagnosis, prognosis, management and treatment. Additionally, REAMS will likely advance future cancer and non-cancer research.
Survival mechanisms orchestrated by the Imprinted and Ancient gene in cancer cells.
Cancers use IDO1 to disable the patient’s cancer-killing immune cells. IDO1 depletes tryptophan. The immune cells cannot function properly at low tryptophan levels, become inactivated and die. It is not understood how the cancer cells themselves overcome deprivation of tryptophan when the immune cells are dying. Our previous research indicates that an imprinted and ancient gene, IMPACT, promotes survival of cancer cells starved of tryptophan. This research investigates whether IMPACT aids cancer cells to overcome chemotherapy and deficiency in essential nutrients. Understanding the role of IMPACT in cancer has high potential to identify novel strategies to combat cancer.
Multi-tumour associated antigen targeted T-cell therapy for acute myeloid leukaemia.
This research investigates the safety and efficacy of harnessing immune cells to eradicate acute myeloid leukaemia (AML). Current treatment of AML, a common type of blood cancer, requires chemotherapy and often stem cell transplantation. However, there remain risks including relapse and potentially life-threatening complications. Here, the patient’s own immune cells are trained in the lab to specifically identify proteins on AML cells. These retrained cells are then given back to patients to destroy the cancerous cells. We will monitor the patient’s response to these cells and the properties of the cells to better understand how this novel therapy works.
Experiences of staff working in children’s blood and cancer centres in New Zealand. It is widely documented in the literature that children’s haematology and oncology can be an environment of high stress. This fellowship will enable me to study the experiences of staff in this area and what influences how they maintain wellbeing working in this environment.
There are two centres for care of children with cancer in New Zealand: the Starship Blood and Cancer Centre (Auckland) and the Children’s Haematology and Oncology Centre (Christchurch). Staff from both of these units have been invited to take part in the study. Findings of the study will be used to inform practice and policy.
Molecular analysis of squamous cell carcinoma of the vulva and the field of cancerisation
Cancer of the vulva is uncommon, and little is known about the mutations resulting in the development of cancer. We suspect cancer arises in a general area or risk field, with early underlying genetic changes that predispose to the development of cancer. We wish to investigate these genetic alterations, and in particular, to identify whether the same or different mutations are present when there are more than one cancer. By understanding how these cancers develop, we hope to improve early detection, identify which women are likely to relapse, and ultimately achieve better treatment to prevent further cancer development.
Discovering the molecular pathways used by HPV to suppress the immune system and cause cancer using CRISPR/Cas9 functional screens.
High-risk Human Papillomaviruses (HPV) can cause a variety of cancers such as cervical, head and neck, and anogenital cancers. These high-risk HPVs have evolved to suppress the immune system so that they can persist in the body, however it not fully understood how this suppression occurs. This study aims to identify the molecular pathway(s) by which HPV suppresses the function of immune cells, using innovative genetic functional screens, utilising CRISPR/Cas technology. Understanding how this suppression occurs will inform the development of therapeutics for the treatment of HPV pre-malignancy and cancer.
New DNA minor groove alkylating agents for arming anticancer antibodies
Antibody-drug conjugates (ADCs) are an emerging class of cancer therapeutics which has stimulated much interest. They have the unique ability to deliver cytotoxic-agents differentially to tumour cells limiting systemic toxicity. Duocarmycins are ultra-potent agents derived from a class of natural products and have the potential to surpass existing agents, however, are limited by poor solubility. We will synthesise and preclinically evaluate a series of novel duocarmycin-based analogues that address vital properties, and which are predicted to provide more effective ADCs.
How do common New Zealand cancers lose their memory?
Cancer often show stem-cell-like features along with loss of DNA methylation, a genome modification that provides a cell with a memory of its identity. The only other human tissues that shows low levels of methylation are the very earliest stem cells of the body and germline. We have discovered a feature that is common to cancer and these embryonic cells that appears to explain the low methylation and loss of memory of cancer cells. We will determine the strength of association in common types of cancer and dissect the mechanisms of this fundamental change.
Immune evasion in GI cancers – what role does the immunoproteasome play?
Gastric cancer is one of the leading causes of death in New Zealand, with limited treatment options available. Our own immune system, trained to recognise and destroy cancer cells, is often circumvented by immune escape strategies employed by tumour cells. We have identified two genes (PSME1 and PSME2) important for the immune response to cancer, that impact survival from stomach cancer, but in opposite ways in different types of stomach cancer. In this project, we aim to understand how expression of these genes affects anti-tumour immunity and how they could be targeted to improve survival from gastric cancer.
Phase Ib randomised, placebo-controlled, double-blinded trial of cimetidine to prevent the nephro-, neuro- and oto-toxicity of cisplatin in patients undergoing chemo-radiotherapy for head and neck cancer
Patients with cancers of the head and neck are often cured with cisplatin chemotherapy and radiotherapy but this can lead to permanent reduction in hearing and kidney function. This trial will study if the drug cimetidine can protect kidneys and hearing from damage due to cisplatin chemotherapy in patients having this treatment for head and neck cancer. If cimetidine is found to be protect against these side effects in this group of patients, further trials will be undertaken to see if it may also be helpful to the many adults and children receiving cisplatin chemotherapy for other types of cancer.
To attend the Trans-Tasman Radiation Oncology Group (TROG) Annual Scientific Meeting 2018, to be held in Hobart, Tasmania, Australia from the 19-22 March 2018.
To attend two meetings. One local workshop (NIWA UV workshop) to be held in Wellington in April 2018 and one international conference (4th International Conference on UV and Skin Cancer Prevention) to be held in Canada in May 2018.
To attend is ESTRO 37 the European Society for Radiotherapy and Oncology, Barcelona, Spain, April ‘18
To undertake a Masters in Health Science, 2018. Semesters 1 and 2, University of Auckland
To undertake a Postgraduate Diploma in Palliative Medicine for Health Care Professionals at Cardiff University