Research interests

Diabetes, stem cells and epigenetics

Diabetes is a chronic metabolic disease in which a person has high blood sugar levels either because the body does not produce enough insulin (type1 diabetes), or because of insulin irresponsiveness (type2 diabetes). The loss of pancreatic beta cells causes insulin dependency in diabetes. While increased circulating insulin may promote pancreatic cancer. Regeneration of pancreatic beta-cell thus provides the next generation of diabetes treatment and elimination of its complications. In this study, the epigenetic modifications on the genome, as illustrated below, that lead to diabetic conditions were explored, to understand the disease etiology and develop possible diagnostic tools.

Epigenetic modifications that drive step-wise differentiation of stem cells to pancreatic beta cells were also explored to assist regenerative medicine technologies for diabetes. See publications.

Iron metabolism in anemia of chronic diseases - Hepcidin Diagnostic

Hepcidin, a hormone secreted by the liver, is a principal regulator of systemic iron homeostasis. It regulates body iron levels by inhibiting intestinal iron absorption and sequestering iron in the macrophages. Hepcidin inhibits cellular iron efflux by degrading ferroportin, the cellular iron exporter as illustrated in the figure below. In this study, hepcidin reduction leads to iron overload in hemochromatosis. Interestingly, hepcidin is elevated in many chronic conditions and contributed to the development of anemia of chronic diseases, possibly due to an evolutionary mechanism to limit iron availability to invading microorganisms. Here, the regulation of iron metabolism by hepcidin and molecular signaling of hepcidin in chronic conditions including chronic infections (e.g. malaria, shown below), chronic inflammation (e.g. obesity and diabetes) and malignancy/cancer were identified. See publications.

Atherosclerosis and inflammatory diseases - preclinical studies of iron chelators and supplements

Coronary heart disease and stroke have claimed the lives of millions of people each year. These diseases result from hypercholesterolemia, coupled with a chronic inflammatory condition of the vascular wall, termed atherosclerosis, that lead to vessel occlusion and various clinical manifestations. It is also commonly a result of diabetic and rheumatoid arthritis conditions. The study aimed to investigate the role of iron in the inflammatory events of atherogenesis, in the course of phagocyte-endothelial cell interactions in the artery, as shown in the video below. This study has revealed an immunomodulatory function of iron in inflammation. Non-transferrin bound iron promotes accumulation of intracellular labile iron and production of oxygen-derived free radicals, leading to cell activation. Activation of endothelial cells is a well-characterized phenotype that leads to endothelial dysfunction in vivo, which not only will initiate the development of atherosclerosis, but also plays a role in thrombosis, promoting vessel occlusion and acute cardiovascular events. In combination with chronic infections, iron enhances infection-induced endothelial activation and aggravates atherosclerosis. Iron alone promotes phagocyte activation and complicates the progression of atherosclerotic cardiovascular diseases. Furthermore, such infiltrating phagocytes are also involved in tumor progression to cancer by providing angiogenesis-associated activities, and neuroinflammation that stimulates development of neurodegenerative diseases.

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PhD thesis, Utrecht University.

Iron fortification and iron chelation could be useful to fine tune immune response. The modifying role of iron chelators and supplements in inflammation identified in this study, offers an additional strategy for prevention and therapy of inflammatory diseases, like atherosclerotic vascular diseases, malignancy and neurodegenerative diseases. See publications.

Thalassemia diagnostic

Thalassemia is an inherited disorder that is caused by mutations or missing genes that affect how the body makes hemoglobin, the main component of the red blood cells. People with thalassemia make less or no hemoglobin, which results in mild or severe anemia. The aim of the study here was to develop molecular genetic-based methods to diagnose many different genetic mutations of thalassemia in many ethnic groups. The methods were also specifically aimed for prenatal diagnosis. Phenotype-genotype variations between the severity of the disease and the type of genetic mutation were also explored. See publications.

Genetic modification of sugarcane

The enzyme, polyphenol oxidase, causes production of dark colorization from phenolic compounds when sugarcane juice is extracted. Paler colored sugar crystals have a better market potential than the dark crystals. In this study, an antisensing technology was attempted here to modify sugarcanes genetically, to produce clones with low polyphenol oxidase activity and lighter sugarcane juice color. See publications.

Protein expression and characterization

Acetolactates synthase, also known as acetohydroxyacid synthase, is an enzyme that catalyzes the first step in the synthesis of branched-chain amino acids (valine, leucine and isoleucine) from pyruvate. Thought to be present only in plants and microorganisms, this enzyme has been the target of many commercial herbicides. A putative human acetolactate synthase gene was identified. This study used a molecular biology technique to clone this putative gene, and express it in E. Coli. Expressed protein was then purified using a liquid chromatography technique and its activity was identified using several enzymatic test techniques. The folded protein did not contain acetohydroxyacid synthase activity. See publications.

Honours thesis, The University of Queensland.