Breast cancer is the most common female malignancy, and a leading cause of death. Although molecular technologies have led to new therapeutic targets for breast cancer, much remains to be done to reduce its societal and economic impact. This project focuses on an emerging cancer drug target – Junctional Adhesion Molecule-A (JAM-A), an adhesion protein that Dr Hopkins (Supervisor; RCSI) and others have implicated in breast cancer. This proposal centres around recent data suggesting that JAM-A controls the expression of HER2 and HER3, key tyrosine kinases associated with aggressive breast cancer. I will test the novel hypothesis that combining a JAM-A antagonist and an anti-HER2/HER3 drug (Pertuzumab) exerts synergistic anti-tumour effects in breast cancer settings. This will be accomplished by: Testing the combination of a JAM-A antagonist and an anti-HER2/HER3 antibody for anti-tumor efficacy in 2D and 3D models of breast cancer in vitro; Using chick embryo xenograft assays (cell line-based and patient-derived xenograft-based) to test the combination of a JAM-A antagonist and an anti-HER2/HER3 antibody in vivo; Identifying new JAM-A antagonists and test them for synergism with an anti-HER2/HER3 antibody in breast cancer settings;Validating a possible JAM-A-HER2/HER3 signalling axis in breast cancer patient datasets and samples. Combining an innovative, multi-faceted approach, and offering an academic multidisciplinary environment which will both complement my industrial skills and enable me to transfer valuable industry-centred knowledge, this project presents a wealth of opportunities to enhance by career prospects and enable a transition back to academia. As there are currently no anti-JAM-A drugs on the market or in clinical trials, this is a timely and important project which will give valuable new translatable knowledge into the treatment of certain aggressive breast cancer phenotypes.

The coronavirus (COVID-19) pandemic has brought health inequalities into sharp focus and exposed the structural disadvantage experienced by people facing the greatest deprivation. Research studies such as Growing Up in Ireland (GUI) and TeenPath at Trinity College Dublin (TCD) and the Royal College of Surgeons Ireland (RCSI) are specifically documenting these inequalities in the lives of children and young people in Ireland pre-COVID-19. This proposal will integrate with the TeenPath study and its aims to centre young people in the development of public health policy targeting adolescent health, with a view to addressing longer term health inequalities revealed and potentially exacerbated by the pandemic. Despite their behaviours being subject to high levels of public scrutiny and social policing throughout the pandemic, young people have limited power to influence society’s response to it. Rapid studies have generated snapshots of the experiences of people living through the COVID-19 outbreak in Ireland, but largely overlook how young people’s routines and emotional wellbeing have adapted. This project will take participatory and social network approaches to investigate how adolescents in Ireland have experienced COVID-19, and will address intersectional dimensions including gender and ethnicity to examine disproportionate impacts of the pandemic on health inequalities. Working with the TeenPath project at RCSI in partnership with TCD, this interdisciplinary project will bring together Public Health, Anthropology and Sociology to deploy innovative approaches such as Photovoice and Social Network Analysis to centre young people in the co-development of public health policy. This co-designed, inter-sectoral and participatory project will contribute to understanding of the impacts of COVID-19 on young people and health inequalities in Europe through policy-focused research, while developing my interdisciplinary skills as an independent public health researcher.

Von Willebrand Factor (VWF) is a protein that blood needs to clot normally. VWF is made by cells that line our blood vessels called endothelial cells. About 1 in 100 people inherit low levels of Von Willebrand Factor. This means that they have a lifelong bleeding disorder known as Von Willebrand Disease (VWD). People with this disease bruise easily and suffer from nosebleeds. They also sometimes bleed after surgery or after having a tooth removed. We do not fully understand why these patients have low levels of VWF. This is especially true for patients whose levels are only slightly less than usual. This group of patients is known as ‘Low VWF’. People with ‘Low VWF’ also often have bleeding that is more than would be expected. To better understand this disorder, we will study why these patients have low VWF levels. We will study if they are making less VWF or clearing VWF from their circulation too quickly. Finally, we will study why these patients bleed by looking at other parts of the clotting system. This will help improve how we diagnose and treat these patients.