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Theme-based Research Scheme 2017/18 (Seventh Round) Layman Summaries of Projects Funded

Theme 1: Promoting Good Health
Project Title: Translational Studies for Elucidating the Tumor Heterogeneity and Molecular Evolution in Metastatic Gastrointestinal Tract Cancers for Personalized Medicine
Project Coordinator: Prof Maria Li LUNG (HKU)

Abstract
The primary cause of cancer deaths is attributed to the development of treatment-refractory metastasis. The challenge is to elucidate the basis for tumor metastasis and heterogeneity and the evolution of drug resistance that contribute to the deadly progression of cancers. Armed with the synergistic expertise and strategic specimens needed, we aim to decipher the molecular landscape for metastatic esophageal tumors utilizing matched primary tumors and their metastatic lymph node tumors, as well as liquid biopsies. The rare circulating tumor cells (CTCs) in the blood, which are the “seeds” for metastasis, offer the opportunity for non-invasive real-time monitoring of cancers to capture the molecular heterogeneity evolving in drug-resistant tumors under selective treatment pressure and to more accurately reflect tumor heterogeneity that may be missed from the original tumor tissues. Blood-based cancer diagnostics provide real-time insight to monitor patients and to enable physicians to optimize cancer treatments of evolving tumors for targeted intervention. Molecular genotyping and next-generation sequencing (NGS) approaches will identify key cancer mutations and other genetic aberrations to guide targeted treatment of metastasis. Utilizing archived formalin-fixed paraffin-embedded (FFPE) tissues from good and poor responders to chemoradiation treatment will provide predictive biomarkers for chemoresponsiveness. The detection of CTCs as early predictive biomarkers for tumor relapse is of vital importance to patients with advanced metastatic cancers in clinical trials and will guide targeted therapies to improve treatment outcomes for metastatic disease. Ex vivo short-term culture of CTCs and establishment of patient-derived xenografts will provide invaluable opportunities for clinical applications to test drug sensitivity, as well as for basic studies to elucidate the functional basis for metastasis. The potential use of CTCs for improving tumor treatment is a strategic opportunity for personalized therapeutics. Gastrointestinal tract (GIT) cancers account for ~22% of cancer deaths in Hong Kong. The focus of our studies will be on esophageal cancer. This proposed study of GIT cancers in Hong Kong using several integrative and novel approaches aimed to elucidate key drivers for tumor metastasis, heterogeneity, and evolution of chemoresistance will allow us to translate our findings into the clinic to improve diagnosis and patient stratification and identify actionable targets for precision medicine. These studies will help to establish real-time analysis and accelerate the technology translation to the clinic to improve metastatic cancer control. Our strategic findings will enhance personalized treatment of Hong Kong cancer patients and improve their overall survival and quality of life.


Theme 1: Promoting Good Health
Project Title: Functional Bone Regeneration in Challenging Bone Disorders and Defects
Project Coordinator: Prof Ling QIN (CUHK)

Abstract
The world population is ageing. According to the Hong Kong Census and Statistics Department, people aged 65 or above will rise significantly from 15% to 36% by 2064. Ageing is associated with many musculoskeletal problems, including primary or secondary osteoporosis (OP), osteoarthritis (OA), and chronic tendon-bone insertion disorder or injury, which often lead to bone fractures, joint deformity and disability. Our current research focuses on these skeletal disorders and injuries with limited repair and healing potential, including osteoporotic fracture, avascular osteoneocrosis (AVN) around joints with extremely high incidence of OA, and tendon-bone insertion reconstruction. A significant reduction in quantity and quality of stem cells, especially bone marrow stem cells (BMSCs), are the most common features in these disorders. Substantial costs are involved in surgeries and subsequent rehabilitations for these severe musculoskeletal conditions and injuries that imposes huge socioeconomic and healthcare burden to the patient, family, healthcare system, and society in Hong Kong and worldwide. Therefore, our collaborative and multidisciplinary research focuses on enhancing treatment outcome of these skeletal disorders or injuries by augmenting the regenerative potential of autologous BMSCs and mobilizing circulating stem cells to bone defects for bone regeneration. To enhance osteogenesis, we will investigate the recruitment of circulating stem cells, mobilization of local BMSCs onto surface of the implanted biomaterials, and cell-matrix signalling with modulation of biophysical stimulation. To achieve our study objectives for targeting above mentioned musculoskeletal problems, this project will be divided into three stages: 1) Osteogenic modulation of BMSCs for skeletal tissue engineering; 2) Investigation on the treatment efficacy of implanted innovative biomaterials and postoperative non-invasive biophysical modulation for maximizing the osteogenic efficacy using our well-established preclinical animal models; 3) Completion of the required biosafety testing for Class III medical implants for product registration and prepare for subsequent clinical trials. Our efforts will focus not only on high quality scientific research but also or more importantly, the research and development (R&D) of effective treatment protocols or strategies for achieving functional bone regeneration of challenging bone disorders. Ultimately, our innovative functional biomaterials and treatment protocols will benefit our patients with a significant reduction on healthcare burden both locally and internationally.


Theme 2: Developing a Sustainable Environment
Project Title: Creation of rechargeable electron-fuels for stationary power supplies and electric vehicles
Project Coordinator: Prof Tianshou ZHAO (HKUST)

Abstract
This theme-based research aims to address the challenges preventing the widespread use of renewable energy. We propose to develop a novel energy storage system that incorporates electrically rechargeable liquid fuels known as e-fuels. This system mainly consists of an e-fuel charger that electrochemically converts electricity into e-fuels, which in turn can be converted back into electricity using an e-fuel cell for end use. The e-fuel charger has no site limitation and can convert intermittent wind and solar power into e-fuels. These e-fuels can be stored indefinitely without quality degradation and transported to wherever needed safely and easily. The electricity generated by e-fuel cells can be integrated into the grid. Unlike any of the existing rechargeable battery technologies that operate on either charge or discharge, the e-fuel storage system can simultaneously store and release electricity, thus forming a stand-alone renewable power supply to power off-grid communities. The stand-alone e-fuel cell even holds the potential to propel next-generation vehicles, offering not only a safer driving experience, but also a refueling time akin to that of gasoline.

To realize this transformative technology, through an integrated theoretical, numerical, and experimental approach, we will create inexpensive and energy-dense e-fuels, conduct crosscutting characterizations and diagnostics of cell operation to identify and eliminate performance-limiting factors at different length scales, and perform multi-scale modeling to achieve the optimal cell design. Ultimately, this research will result in an electricity-fuel-electricity conversion system with unprecedented efficiencies exceeding 80%. The e-fuel storage technology offers an excellent solution not only for grid-scale and micro-grid energy storage, but also for off-grid and distributed energy system power supplies.


Theme 2: Developing a Sustainable Environment
Project Title: Photochemical air pollution in highly urbanized subtropical regions: from micro environments to urban-terrestrial-oceanic interactions
Project Coordinator: Prof Tao WANG (PolyU)

Abstract
Chemical reactions initiated by sunlight produce a variety of gaseous and particulate pollutants, which adversely affect human health and crops and alter climate. Ozone (O3) is a key indicator of the severity of the photochemical pollution and has been regulated worldwide. Yet it is a persistent problem in many urban areas, together with other photochemical pollutants including secondary organic aerosol (SOA). Although it is known that the photochemical pollutants are formed by reactions of oxides of nitrogen (NOx) and volatile organic compounds (VOCs) and that radicals play a key role, recent research has revealed key gaps in understanding the sources and processes of radicals and VOCs and the interactions of emissions from urban/industrial areas, vegetation and oceans. Addressing these issues is crucial in mastering the mechanisms of ozone and SOA production and formulating effective mitigation strategies for urbanized subtropical and vegetated regions.

Hong Kong (HK) and the adjacent Pearl River Delta (PRD) are situated on the South China coast and are one of the most populated and economically vibrant regions in China. Rapid consumption of fossil fuel and a congested urban setting has deteriorated the air quality at both the roadside and on the regional scale. Despite concerted efforts of the HK and Guangdong governments, photochemical pollution has not improved as evidenced by high concentrations of nitrogen dioxide (NO2) at Hong Kong’s roadsides and rising ozone levels in the whole region. Previous studies in the HK-PRD region have focused on urban/industrial areas, but there has been no comprehensive research investigating the problem in an urban-terrestrial-oceanic and micro-meso-synoptic paradigm, which is necessary for understanding and mitigating ozone and other secondary pollutants.

Here we propose to study the fundamental oxidation chemistry of complex mixtures of emissions from urban (traffic)/industrial, terrestrial/biogenic and ocean sources, and to recommend the best strategies to control the photochemical pollution. It develops/applies cutting-edge laboratory, field, and modeling techniques and improves the predictive capability of the modeling system in complex geographical settings like HK-PRD. We will also investigate how the chemistry and dynamics of vehicular exhaust affect roadside air quality – a topic that is not yet well studied but may affect current policy on traffic pollution. This project is in line with China’s research and control priority on air pollution, especially on the worsening photochemical problem, and locally supports the implementation of HK’s Clean Air Plan. Overall, our goal is to conduct world-class research and to strategically support developing a green Mega Bay Area, China, and Asia.


Theme 4: Advancing Emerging Research and Innovations Important to Hong Kong
Project Title: Big Data for Smart and Personalized Air Pollution Monitoring and Health Management
Project Coordinator: Prof Victor On-kwok LI (HKU)

Abstract
We are all entitled to live with dignity in a clean environment. With big data technologies, it is possible to collect complex, heterogeneous, high resolution, personalized, and synchronized urban air pollution, human activity, health condition, well-being, and behavioral data, enabling the generation of smart (real-time and interactive), personal alert and advice to improve the health and well-being of individual citizens, creating new business opportunities and competitive advantage for the IT and health industry in HK and beyond. There are five major challenges. FIRST, urban air quality data is sparse, rendering it difficult to provide timely personalized alert and advice. SECOND, collected data, especially those involving human inputs, such as health perception, are often missing and erroneous. THIRD, data collected are heterogeneous, and highly complex, not easily comprehensible to facilitate individual or collective decision-making. FOURTH, the causal relationships between personal air pollutants exposure (specifically PM(2.5,1.0) and NO2) and personal health conditions, and health (well-being) perception, of young asthmatics and young healthy citizens in HK, are yet to be established. FIFTH, one must determine if information and advice provided can effect behavioral change. To overcome these challenges, our FIRST novelty is to develop a big data framework based on deep learning to estimate smart personalized air quality. Our SECOND novelty includes the deployment of mobile pollution sensor platforms to substantially improve the accuracy of estimated and forecasted air quality data, and the collection of activity, health conditions and perception data, accounting for human in the loop. Our THIRD novelty is the development of visualization tools, and comprehensible indexes which correlate personal exposure with four other types of personal data, to provide timely, personalized pollution, health and travel alerts and advice. Our FOURTH novelty is determining causal relationship, if any, between personal pollutants, PM(2.5,1.0), NO2 exposure and personal health conditions, and also personal health perceptions, based on clinical experiments of 250 young asthmatics and 250 young healthy citizens in HK. An exposure model is developed, trained and verified with real data collected by 250 young asthmatics to further conduct population-based time series health study on 90% of asthmatics in HK. Our FIFTH novelty is an intervention study to determine if smart data, presented via our proposed system, will induce personal behavioral change. Our novel big data technologies and analytical approaches create a unique framework for personalized air pollution monitoring and e-health management, easily transferrable to and applicable in other domains and countries.