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.
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.
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.
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.
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.