Dr Brendan Norman BSc(Hons) MSc PhD

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 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.

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.