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.
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.
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.
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.