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The Research Grants Council funded six projects of Theme-based Research Scheme totalling some $248 million in July. Last month, four of the funded projects were introduced. This article introduces the remaining two projects (supported with a total of $85 million) the research findings of which will greatly benefit the treatment of liver cancer and cardiovascular diseases. The Liver Cancer Genome Project Liver cancer is a highly aggressive tumor that is prevalent in China and Southeast Asia. An annual incidence of about 320,000 new patients has been reported, of which more than 50% occur in China. In Hong Kong, the mortality incidence from liver cancer is about 1,450 cases per year and it currently ranks the 3rd leading cause of cancer deaths. The dismal outcome for the majority of individuals diagnosed with liver cancer is largely attributed to (i) the lack of early diagnostic markers that render patients diagnosed late in the clinical course of disease progression; and (ii) most patients show low therapeutic efficiencies, which consequentially lead to an inferior survival prospect. The median survival for the majority of patients is estimated at about 11 months. Like other cancer types, liver cancer is also a genetic disease. In the areas of liver cancer genome research, clinical diagnosis and treatment of patients with liver cancer, Prof. Nathalie Wong and research team have more than 15 years of broad and extensive experience. In 2011 exercise of the Research Grants Council Theme-based Research Scheme (first-round), Prof. Wong and research team have been awarded HK$4.5 million to undertake a ‘Liver Cancer Genome Project’ aiming to comprehensively delineate the DNA and RNA sequence abnormalities in this cancer. The Project is a joint collaborative program of clinicians and basic researchers from The Chinese University of Hong Kong, The University of Hong Kong, The Hong Kong University of Science and Technology, Beijing Genomics Institute – Shenzhen and The State Laboratory of Oncology in South China. Understanding that current limitations in the clinical management of liver cancer patients is largely due to the paucity of information related to its malignant transformation from liver cirrhosis and the biology of liver metastasis, this Project proposes to conduct large-scale genome-wide analyses to define genetic events which discriminate tumor from cirrhosis and progression to metastatic disease. The deployment of the innovative massively parallel sequencing will offer unprecedented depth, speed and capacity to widely elucidate somatic variations at the genome and transcriptome levels. The instigation of a ‘Liver Cancer Genome Project’ will have strategic importance in cataloguing the genetic blueprint of liver cancer which in turn will provide the foundation for research into identifying targets for therapies, biomarkers for early diagnosis, and prognostic indicators for predicting recurrence. This program is also expected to make significant impact in developing effective disease control strategies for this commonly fatal cancer. Prevention and treatment of Cardiovascular diseases Cardiovascular diseases (CVD) remain the leading global cause of morbidity and mortality. Despite recent advances in the management of cardiovascular risk factors such as hypertension, diabetes, dyslipidemia and obesity, the prevalence of CVD continues to increase worldwide. This highlights the need for new approaches beyond monitoring of conventional serum biochemical parameters to prevent, identify and treat individuals who are at risk of developing CVD. Genome-wide association scan studies show that comorbid traits such as dyslipidaemia and abdominal obesity, are more strongly controlled by genetic factors than their related diseases. Recently, it is reported that genetic polymorphism involved in the regulation of gene expression and thus the serum level of blood lipid. This change in the serum lipid level conferred a significantly increased risk of CAD. This finding emphasizes that genetic studies can offer novel insight into the complex pathophysiology of human diseases that might translate into new approaches to prevent, diagnose and treat CVD. The latest technological breakthrough in the production of human induced pluripotent stem cells enables the generation of patient-specific tissue in-vitro for disease modeling and drug testing. Recent studies by the research team have demonstrated that human stem cells can be generated and differentiated into different tissues, such as vascular smooth muscle cells and mesenchymal stem cells for modeling complex inherited disorders. These techniques should allow us to generate an unlimited supply of patient-specific relevant tissue, such as liver, fat and vascular endothelial cells, and enable study of the relationship between blood lipid related genetic polymorphisms, biological pathways and clinical manifestations. The investigation of the genetic determinants of dyslipidemia in which potential biological pathways can be identified for development of biomarkers, and tested in the in-vitro human stem cells platform for patient-specific disease modeling as well as therapeutic avenues. The ultimate goal is to develop a novel approach to “Personalized Medicine” in the diagnosis and treatment of dyslipidemia, a major risk factor for CVD. Research Grants Council |
