Following the completion of my BSc at the University of Leeds, I went on to study for a PhD, working on a project investigating the post-translational regulation of the LDL receptor (LDLR) and its role in dyslipidaemia. Central to this were cell biological and biophysical studies of proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine protease that modulates the LDLR receptor. It is the third genetic locus for autosomal dominant hypercholesterolaemia (ADH) and has in recent years become an important target for the development of novel cholesterol lowering therapeutics. The work carried out for my PhD involved the characterisation of the protein-protein interaction that PCSK9 forms with the LDLR and the investigation of strategies for its pharmacological inhibition.
After completion of my PhD I moved to the University Hospital of North Staffordshire to train as a Clinical Biochemist, a role that as well as providing formalised clinical scientist training has also allowed me to partake in a significant amount of research. Specific areas of interest include the genetics of dietary folic acid utilisation and pregnancy outcome, the use of laboratory investigations in the diagnosis and monitoring of diabetes mellitus and biochemical markers of cardiovascular disease.
Research and scholarship
- Fetal origins of later onset disease
Genetic and environmental influences of pregnancy outcome and risk of future disease. As a member of the Fetal Epigenetic Group (FEG), I have investigated the association of polymorphisms in genes involved in the methylation of DNA, through the metabolism and utilisation of dietary folic acid, and short-term measures of pregnancy outcome (e.g. birth weight)
Work to investigate whether glycated haemoglobin (HbA1c) has a role in the diagnosis of gestational diabetes mellitus (GDM).
Clinical audit work surrounding the long-term follow-up of women diagnosed with GDM, assessing adherence to NICE guidance
- Cardiovascular disease
As a member of a European working group for cardiac biomarkers, I am involved in European-wide collaborative studies into the appropriate use and clinical effectiveness of biomarkers (e.g. B-type natriuretic peptide, BNP) in cardiovascular disease. I also have interests in the effective use of cardiac biomarkers in clinical practice at a local level.
- Ordinary member - The Association for Clinical Biochemistry and Laboratory Medicine (ACB)
- Member (Young Scientist) – European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Cardiac Markers
- West Midlands Trainees’ Representative – Association for Clinical Biochemistry and Laboratory Medicine (ACB)
Duff, C.J. and Hooper, N.M. (2011). PCSK9: an emerging target for treatment of hypercholesterolemia. Expert Opin Ther Targets 15, 157-168.
Duff, C.J., Scott, M.J., Kirby, I.T., Hutchinson, S.E., Martin, S.L. and Hooper, N.M. (2009). Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J 419, 577-584.
Duff, C.J., Haworth, K.E., Farrell, W.E., Emes, R.D., Ismail, K.M.K., Carroll, W.D., Borthwick, H.A.,
Yates, A.M., Hubball, E., Rooney, A., Khanam, M., Aggarwal, N., Fryer, A.A. (2013). Genetic polymorphisms in the one-carbon metabolic pathway and their association with birth weight. Ann Clin Biochem 50, Suppl 1, 13-14.
Duff, C.J., Hanna, F.W., Hitchin, S.A., Hodgson, E., Stirling, K. and Fryer, A.A. (2012). An evaluation of laboratory testing in the diagnosis of gestational diabetes mellitus: a potential role for HbA1c? Ann Clin Biochem 49, Suppl 1, 88.
Fryer, A.A., Hitchin, S.A., Duff, C.J., Hodgson, E., Stirling, K. and Hanna, F.W. (2011). Does HbA1c have a role as a diagnostic tool in gestational diabetes mellitus (GDM)? Association of British Clinical Diabetologists Autumn Meeting 2011 Abstracts. Practical Diabetes 29, 124a-124e.
Key oral presentations
April 2013 ACB Focus, York, UK. ‘Genetic polymorphisms in the one-carbon metabolic pathway and their association with birth weight’
March 2010 PCSK9 Conference, Nantes, France. ‘The development of small molecules to inhibit PCSK9 function’.
July 2008 Gordon Research Conference: Proprotein Processing, Trafficking and Secretion, New Hampshire, USA. ‘Inhibition of the PCSK9-LDLR interaction: A potential therapeutic strategy’.