Personal Statement
My first degree was Psychology BSc(Hons), which I studied at the University of York. After one year at University College London, where I obtained my MSc in Clinical Neuroscience, I moved to the University of Liverpool in late 2015 to undertake a PhD working with Professors Jim Gallagher and Lakshminarayan Ranganath on the inherited disorder of metabolism alkaptonuria. In my PhD I gained expertise in metabolomic techniques and established new liquid chromatography mass spectrometry (LC/MS) workflows for metabolite analysis which continue to be invaluable to academic and clinical research groups both within and outside of the University of Liverpool. Since obtaining my PhD in 2020, I have branched out to research other areas of translational metabolism including metabolite biomarker discovery endeavours in end-stage lung cancer and metastatic prostate cancer. I am currently funded by the Alkaptonuria Society as a Tenure Track Fellow to lead my own research into new treatment approaches for disorders of neutral amino acid metabolism.

Research Overview
Metabolism is arguably the fundamental biological process, encompassing the entire sum of biochemical reactions necessary to sustain life. These reactions are dynamic and highly regulated to ensure survival, but also extremely sensitive to genetic and environmental influence. My research explores various ways in which metabolism can be altered in specific conditions across life course and how this knowledge can be exploited in translational approaches.

Inherited disorders of amino acid metabolism
This project aims to establish new treatment strategies for disorders of neutral amino acid accumulation with support of the alkaptonuria (AKU) Society patient charity. I am particularly interested in disorders of tyrosine accumulation and therapeutic approaches based on inhibiting the renal reabsorption of neutral amino acids in these conditions. This research has potential to result in the first effective treatment for neutral amino acid accumulation.
Rebecca Brown (PhD supervisee): Rebecca is exploring mRNA as a potential new therapeutic modality for replacement of the enzyme Hgd. Lack of Hgd activity due to genetic mutations is the cause of a serious disease known as AKU. No cure exists for AKU, and existing treatments have major limitations in clinical practice. In simplest terms, we are aiming to deliver the 'message' instructions for production of functional Hgd enzyme to cells of the liver, the organ where Hgd activity is most important. In this project, Rebecca is working with industry collaborators to design and test a variety of candidate mRNA constructs in cell and mouse models of our target disease. A key aspect of this research is to address challenges including specific delivery to the correct site and prolonging the activity of the constructs for sustained enzyme functionality.


Tyrosine metabolism and oxidative stress
My research has helped to establish that certain metabolites of the tyrosine pathway are redox-active and direct sources of free radicals. Studies in inherited disorders of this pathway have shown an association between increases in tyrosine metabolites and chronic degenerative conditions including osteoarthritis and Parkinson’s disease. In this project I aim to define the contribution of chronic exposure to tyrosine pathway metabolites to systemic oxidative stress, which has potential to reveal new disease mechanisms and therapeutic targets. I am using various in vitro and in vivo models to study the effects of tyrosine metabolic alteration combined with manipulation of antioxidant pathways on redox homeostasis.

Metabolite biomarker discovery
I collaborate with various clinical research groups in projects aiming to discover new metabolite biomarkers for diagnosis and monitoring of disease in a range of conditions, including cancer and osteoarthritis. Working with Dr Seamus Coyle (University of Liverpool), I have identified specific urine metabolites that change in the last days of life in patients with lung cancer. In the next phase of this collaboration we are establishing the potential for a simple urine test based on these metabolites to predict whether patients are imminently dying in a palliative care setting. I am also collaborating with Professor Isabel Syndikus (Clatterbridge Cancer Centre) on a metabolite biomarker discovery project in metastatic bone disease, which is particularly common in prostate cancer; over 80% of patients with metastatic prostate cancer have bone metastasis. In previous research we have identified specific compounds including novel bone markers indicating evidence of bone metastasis. This collaboration has potential to result in a new non-invasive test to monitor bone metastasis from prostate cancer based on specific urine metabolites and to reduce the burden of imaging episodes in metastatic prostate cancer.