发布时间 :2013-05-09  阅读次数 :2173

【报告题目】Correlation of genetic and cardiovascular risk markers with blood telomere length–understanding role of telomere in cardiovascular disease

【报告人】Dr. WANG Xueying,

Assistant Professor and Principal Investigator at Department of Biochemistry,

NUS, Singapore

【报告时间】 2013年5月20日 上午 10:00-11:00

【报告地点】 闵行校区, 生物药学楼1号楼 (大红楼) 105室




Dr. Xueying Wang was one of the first scholars awarded by the Economic Developmental Board of Singapore (EDB)-Glaxo Wellcome (GSK) for the pursuit of a degree in life sciences. She graduated from the University of Toronto and then went on to pursue her Ph.D. at the Institute of Molecular and Cell Biology (IMCB), Singapore, where she conducted research in the areas of mouse developmental biology and signaling transduction under the mentorship from Prof. Baojie Li. In 2006, Dr. Wang joined Prof. Elizabeth Blackburn’s lab in the University of California, San Francisco (UCSF) where she held a Susan Komen Breast Cancer Foundation fellowship. During her stint at UCSF, she has been a highly enterprising and collaborative researcher. Her research centres on telomeres, the protective ends of the chromosomes, and on telomerase, the enzyme, which Prof. Blackburn originally discovered. Together with Prof. John Sedat, they explored a live cell dynamic approach to telomere regulation. The topic of how chromosomes are protected by telomeres and the enzyme telomerase has won Prof. Blackburn the Nobel Prize for Physiology or Medicine in 2009. Dr. Wang is currently developing a novel anti-cancer therapy based on telomerase inhibitors and aims to decipher the mechanisms of telomere attrition-induced body dysfunctions using both human disease samples and mouse models to provide new therapeutics for telomerase-regulated human diseases. Dr. Wang has won many awards including the AACR-MERCK award and was appointed the Principal Investigator of her lab in the National University of Singapore in Dec 2008 to further develop the fundamental biological research into this promising new avenue of telomerase for the potential treatment of cancer and aging disorders.



Telomeres at the ends of chromosomes are critical for maintaining chromosomal stability and cellular genomic integrity. Telomere length (TL) shortens with age and can be accelerated through oxidative stress. Epidemiologic studies have shown that average TL of peripheral blood or buccal DNA, a surrogate biomarker of telomere abnormality, is related to risk of various chronic diseases such as cardiovascular disease (CVD) and cancer, all of which increase in incidence with ageing. Dietary nutrients and genetic factors also influence TL; accelerate TL shortening in some cases. However, the link is not clear and the mechanism is unknown. Using a pilot study of about 500 human blood samples from the Singapore Chinese Health Study (SCHS) with well characterized dietary determinants and known risk markers of CVD already measured in the cohort (e.g., cholesterol levels in hypercholesterolaemia condition of CVD), we performed leukocyte TL association studies. We found TL of participants shortens with increasing chronological age, correlated with literature. Statistical analysis also reveals sexual dimorphism in TL where females had longer mean TL than males. Interestingly, smokers have a significantly shorter TL than non-smokers, which implies an increased exposure to oxidative stress. This is the first report ever in an Asian population with genetic homogeneity from the SCHS. More importantly, TL correlated inversely with cholesterol level and it is mainly with low density lipoprotein, suggesting the development of TL as an early risk marker of CVD. With the pilot 500 samples and employing arrays, chips, and molecular telomere biology techniques, we aim to find detailed link of TL to CVD risk markers and whether this link could be influenced by primary genetic (single nucleotide polymorphisms) and/or secondary (nutrition and dietary determinants) causes of CVD. Finally, we aim to investigate the possible mechanistic pathways involved and thereafter devise appropriate therapeutic agents against CVD risk.