Professor of Mitochondrial Pathology, Newcastle University
Honorary Consultant Clinical Scientist, Newcastle upon Tyne Hospitals NHS Foundation Trust
Head of Laboratory, Newcastle NHS Highly Specialised Mitochondrial Diagnostic Laboratory
Scientific Director, Yorkshire and North East Genomic Laboratory Hub
Following a Bachelor’s degree in Biochemistry and an introduction to mitochondrial bioenergetics by Dr Stan Sherratt, I undertook graduate training in the Departments of Clinical Neuroscience and Child Health under the supervision of Professor Doug Turnbull and Professor Kim Bartlett, obtaining my PhD in 1994. I was appointed to a Lectureship in 2001, Senior Lecturer in 2005 and a Chair in Mitochondrial Pathology, Newcastle University in 2007. I am also an Honorary Consultant Clinical Scientist, Newcastle upon Tyne Hospitals NHS Foundation Trust, leading the National-Commissioned Highly Specialised NHS Mitochondrial Diagnostic laboratory and following NHS England’s recent reconfiguration of Genomic services have been appointed to the role of Scientific Director of the Yorkshire and North East Genomic Laboratory Hub, the regional partnership of accredited NHS diagnostic molecular genetics laboratories in Leeds, Sheffield and Newcastle delivering genomic testing, including whole genome sequencing, to the 8.5M population of the North East of England.
I began my research by studying the biochemical and molecular genetic basis of mitochondrial respiratory chain and fatty acid oxidation disorders, with a particular emphasis on understanding the control of oxidative phosphorylation on fatty acid β-oxidation flux. Following periods of post-doctoral research focussed on investigating the role of mitochondrial DNA (mtDNA) mutations in diabetes and the development of experimental gene therapy strategies for the treatment of heteroplasmic mtDNA disorders, I have developed a programme of research linked to unique patient cohorts investigated through the multidisciplinary NHS Mitochondrial Diagnostic laboratory. This aims to identify and characterise novel mtDNA and Mendelian mitochondrial genetic defects causing mitochondrial disease, dissect the molecular mechanisms leading to cellular dysfunction and translate this information to improvements in diagnostics, clinical care and treatment.
The overall aim of my research is to use biochemical, molecular genetic and cell biological tools to diagnose and characterise the molecular pathology associated with human mitochondrial (both mtDNA-derived and Mendelian) disorders so as to understand disease mechanism and benefit patient care through the development of treatments and provision of accurate genetic advice.
This work is wide-ranging, encompassing projects aimed at:
1. defining the prevalence, natural history and genotype:phenotype correlations associated with mitochondrial disease
2. improving the laboratory diagnosis and options for prenatal and preconceptional genetic screening
3. documenting the neuropathological changes associated with mitochondrial genetic disease to delineate the molecular mechanisms leading to neuronal loss and neurological deficits in patients with mitochondrial disease
4. using next generation sequencing strategies, including whole exome and whole genome sequencing, to identify novel disease genes associated with a range of mitochondrial oxidative phosphorylation defects with the broader aim of characterising the mechanisms which underlie post-transcriptional mitochondrial gene expression. My laboratory uses patient tissue, cell lines, CRISPR-cas9 generated lines and additional models to study the functional consequence of mutated mitochondrial proteins.
Uniquely positioned at the diagnostic-research interface, I work closely with all the Wellcome Trust Centre PIs and collaborate extensively with a number of international clinical and basic scientists.