I was appointed Professor of Discovery and Experimental Medicine and Director of the Centre for Advanced Discovery and Experimental Therapeutics in 2011. I have also had a Chair at the University of Auckland, New Zealand, since 1995.
My research over the past decade has had two closely related aims: firstly, to elucidate the mechanisms of diabetic organ damage; secondly, to determine the metabolic basis of age-related dementia, starting with Alzheimer's Disease and Huntington's Disease and continuing with Parkinson's disease dementia and vascular dementia; and finally to use diabetic organ damage (particularly neurodegeneration) as a 'Rosetta Stone' to find mechanistically relevant perturbations that might be shared among them. This approach is based on epidemiological evidence and molecular data linking diabetes with common age-related dementias.
I was elected a Fellow of the Royal Society of New Zealand in 1998 and a Fellow of the Academy of Medical Sciences (UK) in 2013.
After completing my medical and pathology training in New Zealand, I was awarded a Nuffield Medical Fellowship to study for a doctorate with Ken Reid in the MRC Immunohistochemistry Unit at the University of Oxford, where I discovered and isolated the beta-cell hormone amylin from the pancreatic islets of type-2 diabetes patients. Starting in Oxford and continuing in the USA and back in New Zealand, I characterised the two intertwined structure-activity relationships of amylin as a hormone and as a cytotoxic amyloid-forming protein. In 1987, I founded and was sole scientific founder of Amylin Pharmaceuticals Inc., a biotechnology corporation in San Diego, California, USA. The company, where I was Chief Technical Officer/Executive Board Member until 1992, was set up to progress amylin as a drug lead, which underpinned the development of a new class of anti-diabetic medicines, termed amylin agonists. This ultimately lead to the licencing of pramlintide, the first non-aggregating amylin chimaera, Symlin®, approved by the US Food and Drug Administration for treatment of diabetes in 2005.
In 1993, I returned to New Zealand to become Associate Professor, then Professor at the University of Auckland, where I continued my research into amylin and other peptide hormones, demonstrating, for example, that amylin becomes deficient in both major types of diabetes and that human amylin causes islet beta-cell degeneration via the FAS/FASL/FADD/caspase-8 signaling pathway. In parallel my research has been translated into further new first-in-class therapeutic molecules for the treatment of diabetes: these are the synthetic GLP-1 agonists Byetta® and Bydureon®; and into the discovery of new classes of molecules that suppress amylin-mediated beta-cell death, which also have the potential to be new anti-diabetic agents.
More recently both in Auckland and since my appointment at The University of Manchester, I have shown that defective copper regulation is a substantive pathogenic mechanism causing diabetic organ damage in the heart and kidneys, and have identified severe metabolic perturbations in glucose, sorbitol, fructose, urea, vitamin B5 and copper that potentially cause neurodegeneration in age-related dementias.
I am also active in developing Intellectual Property related to my investigations. In addition to my publications in scientific journals, I have been awarded 47 international patents. I consider these patents to be just as important as the journal articles, because they underpin the processes by which my research can be translated into new medicines, and also because they provide independent evidence of the novelty, originality, and utility of the research.
BSc, BSc (Hum Biol), MBChB, Dip Obst, DPhil (Oxon), FRCPA, DSc (Oxon)
Visiting Professor of Experimental Pharmacology, Jinan University1 Nov 2018
→ 31 Oct 2023
Visiting Professor and High-End Foreign Expert to Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences1 Jan 2014
→ 31 Dec 2019
Visiting Research Professor of Pharmacy and Pharmacology, Li Ka Shing School of Medicine, University of Hong Kong2014
Visiting Professor of Experimental Therapeutics, Medical Sciences Division, Oxford University2010
Professor of Biochemistry and Clinical Biochemistry, and of Medicine, University of Auckland1995