Proteomics to decipher diseases
Proteomics refers to the large-scale study of the proteins produced by a given organism, including their structures and functions.
Such study requires diverse research skills with instrumentation, protein chemistry, and bioinformatics, etc., as proteomics emerged only in the past two decades as an interdisciplinary subject.
Professor Sze Siu Kwan Newman, of Nanyang Technology University’s School of Biological Sciences, is leading a multidisciplinary research team to develop and apply advanced proteomic technologies to decipher human diseases, elucidate epigenetic regulatory mechanisms and chromatin structure, and characterise microbial biocatalysts for viable biorefinery processes.
Sze’s team works closely with clinicians and clinical scientists from the National University Hospital, the National Cancer Centre, and has collaborated with a number of overseas institutes, including the Interuniversity Cardiology Institute of The Netherlands, and the University of Ulm Medical Centre in Germany. The team is also aiming to establish a ‘biobank’ of patients’ medical records and clinical data for in-depth analyses and cross reference, so as to help detect and catalogue biomarkers which signal the presence of disease.
Over 50 per cent of annual deaths in developed countries can be attributed to heart disease, stroke, and cancer. Sze and his team have been focusing on discovering the common molecular pathophsiologies in these three major lethal diseases. Having identified hypoxia as a common causative element in the development of the three major diseases, the team has been studying hypoxia model systems for each of the medical conditions using cell lines, animal models, and clinical samples.
Regarding Ischaemic heart disease and stroke, the team has developed a novel proteomics platform which integrates in vitro studies of cellular hypoxia with in vivo animal models of Ischaemia to identify potential therapeutic targets for the prevention of cellular and tissue damage in human patients. Together with the Interuniversity Cardiology Institute of the Netherlands, the team has discovered a biosignature of protein biomarkers from atherosclerotic plaque and plasma microvesicles that contains information predictive of secondary cardiovascular events on top of traditional risk factors.
On the subject of cancer treatment, it is often overlooked that hypoxia is an important factor in cancer development. Indeed, tissue hypoxia promotes the evolution of cancer cells towards more aggressive, therapy-resistant profiles. Sze’s team has designed an in vitro model of cancer development under conditions of variable hypoxia stress that can be monitored using quantitative proteomic analyses. Cancer cells initially grown under normal oxygen conditions are subjected to three oxygen-level conditions that reflected the phases of a tumour’s development. Thus the researchers are able to determine the modulation processes by low-oxygen conditions. In a paper in the journal Molecular & Cellular Proteomics (2013), the team has reported the identification of a potential new drug target called HP1BP3, which appears to be a key switch in promoting cancer cell proliferation and survival.
According to Sze, the ultimate aim of his research is to apply proteomic technology to solve biomedical and biological problems which impact on human health and benefit the widest population.
Reflecting on his academic career path, Sze is glad to have received multidisciplinary research trainings in chemistry, chemical physics, protein chemistry, and mass spectrometry at leading institutes in both Asia and North America. Such experience is so beneficial to him that today when proteomics is still at its infant stage, he can relate different branches of knowledge and explore research methods from various angles.
Professor Sze graduated from the University of Hong Kong with a bachelor’s degree in chemistry and a doctoral degree in chemical physics. During 1995 and 2002, he held two subsequent postdoctoral fellowships at the University of Toronto and University of Waterloo, concentrating on chemical physics and protein chemistry, and later became a visiting proteomic scientist at Cornell University. He joined the Genome Institute of Singapore in 2002, and since 2006, has fully dedicated to his academic role at the School of Biological Sciences at the NTU. Professor Sze has established NTU’s proteomics facility and serves as its director.
Professor Sze has received the award from Croucher Foundation for two times, first time in 1990 a studentship at the University of Hong Kong, second time in 1994 a fellowship at the University of Toronto.
To view Professor Sze’s NTU page, please click here.