This research area covers: 1) Identifying novel targets for the treatment of diabetic complications, including heart failure and nephropathy; 2) Use of MRI technology to identify diabetes risk factors in different ethnicities; 3) Finding natural compounds from New Zealand marine organisms for the treatment of cancer, heart disease and diabetes.
Spermine/Spermidine Acetyltransferase as therapeutic target for diastolic heart failure in Streptozotocin-induced diabetic rats
Diabetic heart failure develops in most diabetic patients and its development is independent of ischemic heart disease and hypertension. Currently, this condition is the most common (>50%) type of heart failure worldwide, including New Zealand. Metabolic alterations in diabetes are closely associated with diabetic heart failure. Polyamine metabolism may influence such metabolic changes. As the polyamine metabolism has previously been shown to have implications in various complications of diabetes mellitus, we propose that the induction of the rate limiting enzyme of polyamine metabolism (Spermine/Spermidine Acetyltransferase - SSAT) may provide a unique, novel treatment approach for diabetic heart failure. It is also important to find an effective treatment for diabetes related heart failure, because the underlying mechanism for this condition is entirely different from the non-diabetic heart failure, thus the routine treatment of heart failure could be ineffective. We have planned the current project to study the therapeutic effect of three SSAT inducers in a diabetic rat model, which have been previously shown as a good experimental model of diabetes related heart failure.
Phthalimide analogues as new chemotherapeutic agents for the treatment of cancer
The structure activity relationship shows substitution on nitrogen position of glutarimide ring improves thalidomide’s anti-tumour activities. In addition, copper was determined as a switch in angiogenesis process in tumour cells. Triethylenetetramine (trien) as a copper chelator is currently considered as a cancer therapy of anti-angiogenesis. Therefore, a novel group of compounds can be synthesized by structural combination of two compounds thalidomide analogues and trien at nitrogen position of glutarimide ring in the structure of thalidomide analogues. The synthetic compounds are involved in in vitro and in vivo characteristic determination. The individual function from each compound is not statistically and significantly affected by synthetically structural combination in in vitro study, also the clinical efficacy outcome is expected to possess synergetic effects from two compounds in in vivo mice with human MM model.
PVT 1 as a potential target for the treatment of diabetic nephropathy
Briefly, diabetic nephropathy is a severe long-term complication of diabetes. It is the leading cause of kidney failure or end-stage renal disease (ESRD) which accounts for most of the reduced life expectancy in diabetic patients. There is no effective treatment option to prevent the onset of diabetic nephropathy and its progression to end-stage renal disease at present. Recent research has identified a gene called PVT1, which is closely associated with the development of diabetic nephropathy and susceptibility to ESRD in diabetes. However the molecular action of PVT1 remains poorly understood. The project aims to characterize the role of PVT1 along the development of diabetic nephropathy and to study the effect of PVT1 inhibition on the onset or progression of diabetic nephropathy in a diabetic model. It is hoping that the findings can lead to better understanding of the mechanism of PVT1 on diabetic nephropathy.