Career Summary: Since 2014 John has served as Director, Curtin Health Innovation Research Institute, Curtin University, hosting >300 researchers addressing the national health priority of chronic diseases with ageing. John has been funded principally via NHMRC for >30 years and held several prestigious Fellowships. John was awarded the NHMRC-Marshall and Warren Award for most innovative and potentially transformative research (all categories) for his pioneering studies in ageing and neurocognition.
Translational research outcomes:
Cardiovascular: John is a physiologist with 35 years of medical research experience, broadly in nutritional physiology, metabolism, lipids, vascular biology and neurosciences. In a historical career context, John provided first equivocal evidence that postprandial lipoproteins become entrapped within the subendothelial space of arterial vessels contributingdirectly to atherosclerotic process (high citations). A major body of work he led over 20 years led to the development of the pharmacological agent Ezetimibe, targeting postprandial lipoprotein metabolism for reducing risk for coronary artery disease. John was recognized by multiple industry sponsored invitations across North America and to European centres of medical research excellence.
Alzheimer’s disease: John has led a series of studies resulting in the paradigm shifting hypothesis that Alzheimer’s disease is a consequence cerebral capillary microvascular corruption caused by exaggerated exposure in blood to lipoprotein-beta amyloid. John’s team were the first to show age- associated blood-brain barrier disruption, positively associated to lipoprotein-amyloid homeostasis; that amyloid is secreted from lipogenic organs (liver and intestine) as an apoprotein of nascent triglyceride rich lipoproteins; that the latter compromise capillary integrity, resulting in blood-to- brain parenchymal extravasation; neurovascular inflammation and accelerated cell death. In a seminal publication in 2021 (PLOS Biology, >50,000 reads within 2 months of publication; 69 international news outlet reports, Altmetric impact score of 694, which is in the top 1% of more than 20,000,000 articles ever published), John genetically engineered mice to synthesise amyloid restricted only in liver and demonstrated equivocally that the blood-to-brain neurodegenerative pathway may explain late sporadic Alzheimer’s disease. John also discovered an historic drug which suppresses lipoprotein amyloid secretion concomitant with preservation of capillary integrity and sparing of cognitive function. The latter findings led to award in 2020 of the MRFF-Probucol in Alzheimer’s trial for which he serves as Principal Investigator. John has also developed a pro-drug of probucol enabling targeted effects with reduced off-target consequences (Australian provisional patent: 2021904008).
Pain: Based on his positive findings in preclinical studies, John has developed a nutraceutical formulation targeting capillary tone and microvascular inflammation. The approach is based on his hypothesis that chronically exaggerated capillary constriction and associated microvascular inflammation triggers pain. In an ongoing clinical trial in migraineurs which John leads (ACTRN12621001476820), interim analysis suggests a significant reduction in migraine frequency and severity. Migraine pain is the most significant neurological burden affecting particularly women. Based on anecdotal evidence provided via the migraine trial, the formulated preparations will now also be trialled in 2023 in women with endometriosis; and in Australians with rheumatoid arthritis. Multiple Sclerosis: John has led the preclinical studies which herein demonstrate profound preservation of myelin integrity in aggressive models of demyelination as consequence of the provision oral supplementation with purified formulated nutraceuticals.