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Theme-based Research Scheme - First Round Layman Summaries of Projects Funded

Theme 1: Promoting Good Health
Project Title: The Liver Cancer Genome Project: translating genetic discoveries to clinical benefits
Project Coordinator: Prof Nathalie Wong (CUHK)

Abstract
Hepatocellular carcinoma (HCC) is a highly aggressive tumor that is prevalent in China and Southeast Asia. In Hong Kong, HCC is a major health problem that attracts social attention and resource. The dismal clinical outcome for the majority of individuals diagnosed with HCC is largely attributed to limited understandings on the malignant transformation of HCC from its histological precursor, namely liver cirrhosis, and the paucity of information related to the biology of hepatic metastasis. Under this grand challenge, we propose to conduct large-scale genome-wide analyses to define the genetic events which discriminate tumor from cirrhosis, and during the progression to metastatic disease. We propose to deploy the innovative massively parallel sequencing that offers unprecedented depth and speed, and also to exploit its capacity to comprehensively elucidate copy number and structural 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 HCC which will in turn provide the foundation for research into identifying targets for therapies, biomarkers for early diagnosis, and prognostic indicators for predicting recurrence. We expect this program will make significant impact in developing effective disease control strategies for this commonly fatal cancer.


Theme 1: Promoting Good Health
Project Title: Massively Parallel Sequencing of Plasma Nucleic Acids for the Molecular Diagnostics of Cancers
Project Coordinator: Prof Dennis Yuk-ming Lo (CUHK)

Abstract
Cancer is the top killer in Hong Kong and many parts of the world. The lack of effective tools for the timely detection and dynamic monitoring of cancer has hindered efforts in combatting cancer. The Project Team is a world-leading group in the biology and diagnostic applications of plasma nucleic acids. The advent of massively parallel DNA sequencing has created a paradigm shift in genomics research. The group is among the first to demonstrate the use of massively parallel sequencing as a diagnostic tool. The group has pioneered a number of novel approaches for applying massively parallel sequencing for the detection and analysis of plasma nucleic acids at an unprecedented level of sensitivity, resolution and comprehensiveness. In this project, the group proposes to lay the conceptual and technological foundation for applying massively parallel sequencing of plasma nucleic acids as a detection and monitoring tool for cancer. Such an approach would allow the development of generic cancer detection tests with broad population coverage and unlike the approaches available to date where only a subset of cancer-related molecular alterations are targeted at each instance. Coupled with the proven analytical power of massively parallel sequencing, such developments are expected to enable the timely detection, real-time monitoring and accurate prognostication of cancer. These goals, when realised, would significantly impact cancer management and bring health benefits to the citizens of Hong Kong and worldwide. This project is also expected to generate valuable intellectual properties which would stimulate the developments of biotechnology in Hong Kong.


Theme 1: Promoting Good Health
Project Title: Personalized Medicine for Cardiovascular Diseases: From Genomic Testing and Biomarkers to Human Pluripotent Stem Cell Platform
Project Coordinator: Prof Hung-Fat Tse (HKU)

Abstract
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 (GWASs) studies show that comorbid traits such as dyslipidaemia and abdominal obesity, are more strongly controlled by genetic factors than their related diseases. A recent meta-analysis of GWASs of over 100,000 individuals identified 95 loci associated with lipid traits, including 59 new ones. Although it has been criticized that the common variants identified through this approach may have too small an effect to be of biological relevance, the identification of novel biological pathways that link these genetic variants to CVD risk may lead to the development of new biomarkers as well as targets for therapeutic intervention. Recent study discovered that genetic polymorphism involved in the regulation of gene expression at chromosome 1p13 loci can affect the expression of sortilin 1 and thus the serum level of blood lipid-low-density lipoprotein cholesterol (LDL-C). This change in the serum LDL-C level conferred a significantly increased risk of CAD. This study emphasizes that GWASs 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 (iPSC) enables the generation of patient-specific tissue in-vitro for disease modeling and drug testing. Our recent studies have demonstrated that human iPSCs can be generated and differentiated into different tissues, such as vascular smooth muscle cells and mesenchymal stem cells for modeling complex inherited disorders. These techiques 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, eQTLS, biological pathways and clinical manifestations. We propose to combine our expertise and strength in GWAS and their validation, based on our existing large clinic and population-based databases, biomarkers discovery and development and iPCS platform to develop a novel approach to "Personalized Medicine" in the diagnosis and treatment of dyslipidemia, a major risk factor for CVD in the local Chinese population. This approach offers the chance to investigate the genetic determinants of dyslipidemia in which potential biological pathways can be identified for development of biomarkers, and tested in the in-vitro human iPSC-based platform for patient-specific disease modeling as well as therapeutic avenues. The ultimate goal is to optimize individual medical care, including diagnosis, treatment and prevention strategies for CVD. This will result in an unprecedented customization of patient care to promote good health.


Theme 1: Promoting Good Health
Project Title: Cell-based Heart Regeneration
Project Coordinator: Prof Ronald Adolphus Li (HKU)

Abstract
Heart diseases are a major cause of death worldwide. Loss of cardiomyocytes (CMs) due to aging or diseases is irreversible. Current therapeutic regimes are palliative; in end-stage heart failure, transplantation remains the last resort but is significantly hampered by a severe shortage of donors. Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency to differentiate into all cell types, including CMs. Direct reprogramming of adult somatic cells to induced pluripotent stem cells (iPSCs) has been achieved. The availability of hESC/iPSCs has enabled researchers to gain novel biological insights and to pursue heart regeneration. Despite these promises, substantial hurdles remain for translating into cell-based therapies and other applications (e.g., disease modeling, cardiotoxicity and drug screening). Based on our team's own work in the past decade, we have identified MAJOR GAPS: hESC-CMs have immature properties, small physical size (~10x<adult CMs), absence of ordered organization, poorly-defined immunobiology and sub-lineage specification, uncertain safety and efficacy. To address these, we have assembled a multi-disciplinary team of world-class experts to work collaboratively on a proposed 5-year program. Our investigators are authorities in bio-artificial pacemaker (Prof Ronald Li from The University of Hong Kong (HKU), American Heart Association's Best Basic Study of 2005, Ground-breaking Clinical Study of 2006, generation of first genetically-engineered hESC-CMs), cardiac progenitor (Prof Kenneth Chien from Harvard Stem Cell Institute, world's first discovery in 2005), hESC bio-imaging (Prof Joseph Wu from Stanford Stem Cell & Regenerative Medicine Institute, AHA's Best Basic Study of 2006), Ca2+ signaling (Prof Heping Cheng from Peking University (PKU), first discovery of sparks) and first-in-man gene therapy for heart failure (Prof Roger Hajjar from Mount Sinai School of Medicine (MSSM)). In addition to cardiobiology, our members are pioneers of the technologies that they routinely use or develop: electrophysiology (Prof Ronald Li-HKU), Ca2+ cycling (Prof Hon Cheung Lee-HKU, Prof Andrew Miller-Hong Kong University of Science and Technology, Prof Roger Hajjar-MSSM, Prof Heping Cheng-PKU, Prof Xiaoqiang Yao-Chinese University of Hong Kong), reprogramming (Prof Douglas Melton-Harvard Stem Cell Institute), cardiac tissue engineering (Prof Kevin Costa-MSSM), biorobotics (Prof Dong Sun-City University of Hong Kong), bioinformatics/genomics (Prof Si Lok-HKU, Prof Kenneth Boheler- National Institutes of Health), etc. Successful project completion will generate a cadre of locally trained stem cell biologists, significantly advance the field, and lead to translations that benefit the community. In the past decade, our investigators have obtained over 25 patents on the topics, and been involved with at least five start-up biotech companies. The proposal will be executed in HK, with knowledge transfer among partner institutions via well-coordinated exchange programs. By uniquely capitalizing on existing expertise and equipment already invested and available in HK, this flagship application from the multi-institutional collaborative HK Stem Cell Initiative (HKSCI) serves as a first vehicle to develop focused strengths in Stem Cell & Regenerative Medicine.


Theme 2: Developing a Sustainable Environment
Project Title: Challenges in Organic Photo-Voltaics and Light-Emitting Diodes- A Concerted Multi-Disciplinary and Multi-Institutional Effort
Project Coordinator: Prof Vivian Wing Wah Yam (HKU)

Abstract
With the huge and fast-growing population and an upcoming depletion of fossil fuels, there is an urgent need and pressing demand for a low carbon or carbon-neutral energy economy. Development of clean renewable energy and new measures for reducing the energy demand are definitely needed to meet the grand challenges. Organic light-emitting diodes (OLEDs) are recognized as a viable candidate for launching of a more efficient solid-state lighting system, while the discovery and development of efficient organic photovoltaic (OPV) devices for solar energy conversion will have a major impact in addressing the energy issues. However, low power efficiencies, materials and device stability and relatively high manufacturing cost of OLEDs and OPVs present a major challenge for commercialization, and new breakthroughs in the development of new materials and fabrication processes that are much cheaper and more processable for efficient OLEDs and OPVs are highly desirable. In this project, we aim to integrate multi-disciplinary and multi-institutional efforts with complementary expertise to foster new interdisciplinary collaborations to meet the grand challenges related to energy. Particularly, we target to develop (i) libraries of patentable, robust, and industrial competitive phosphorescent materials for OLED applications, (ii) new classes of patentable low bandgap OPV materials, (iii) highly efficient and new synthetic methods for solution-processable OPV materials, (iv) in-depth understanding of the physics and controlling factors affecting the device performance of OLEDs and OPVs, and (v) industrial-competitive technologies for active matrix OLEDs and large area OLED and OPV devices. The success of the proposed project would not only generate Hong Kong- and China-owned intellectual property (IP) rights, patents and technological know-how, but also creates new opportunities for knowledge and technology transfer to national and international industrial partners. These would definitely promote Hong Kong towards a low carbon economy and to improve the image of Hong Kong as a city of high clean renewable energy and environment awareness.


Theme 3: Enhancing Hong Kong's Strategic Position as a Regional and International Business Centre
Project Title: Transforming Hong Kong's Ocean Container Transport Logistics Network
Project Coordinator: Prof Chung-yee Lee (HKUST)

Abstract
Hong Kong as a port city is facing ever increasing competition from other ports in the region and doubts have been cast on its future as a logistics center. The major cities in the world, for example London and New York, have evolved from port cities that mainly handled physical goods into modern financial and information hubs, moving most of the ocean container business to less expensive neighboring port cities. On the other hand, ports such as Rotterdam still depend on physical flows. It is important to consider what path Hong Kong should follow. A unique distinction is that the future of Hong Kong will largely depend on the cooperation between Hong Kong and the Pearl River Delta (PRD). Against this backdrop, we believe that Hong Kong should follow a mixed model, i.e., it should shift its focus from physical flow toward financial flow and information flow, yet still maintain logistics as the foundation for other types of flows and services. Hence, Hong Kong and Shenzhen's ports can be viewed as a joint node in the global supply chain network. This logistics foundation will serve to promote Hong Kong as a regional and international financial and service hub. Ocean container logistics, the lifeline of almost any global supply chain, if developed properly, can serve as a solid foundation for old and new businesses alike and attract new opportunities to other important business sectors such as the financial industry.

The proposed project has two major goals. (1) To establish Hong Kong as the research hub for maritime logistics and supply chain management. A team of researchers from Asia and Europe with extensive knowledge in this area will be brought together for this purpose. The team will study holistically ocean container transport supply chain networks around the world, at both the strategic and tactical levels. The issues to be addressed are intellectually challenging and have huge potential impact on Hong Kong. The team is geared toward generating state-of-art research on ocean container logistics networks, which is a very important emerging area in academia. The team will also develop decision support systems for Hong Kong's ocean container supply chain network. (2) To develop an in-depth understanding of Hong Kong's role as a port city and its future direction. Hong Kong is currently facing many challenges that call for strategic repositioning but it is also presented with many opportunities that should be carefully explored. This proposed project will contribute to the transformation of Hong Kong's ocean container transport logistics network in the city's quest to remain and grow as a regional and international business center.