TGF-β Signaling in End-Stage Organ Diseases: Molecular Mechanisms and Therapeutic Implications
Project Coordinator: Prof Hui-yao Lan (CUHK)

Tissue scarring or fibrosis is a common pathway leading to the permanent loss of functional activities of the organ, called end-stage of organ diseases. These diseases are the most life-threatening, including chronic cardiovascular disease, liver cirrhosis, and chronic lung and kidney diseases. However, the pathogenic mechanisms of these diseases are largely unclear and treatments remain non-specific. Thus, the present study aims to establish an integrated basic and clinical research platform to investigate new molecular mechanisms and pathways of tissue scarring and to develop a novel, specific, and effective therapy for prevention and treatment of these end-stage of organ diseases.

The Brain Mechanisms to Use Electronic "Bat Ears" to Replace Vision: From Human to Animal Users
Project Coordinator: Prof Jufang He (PolyU)

The proposed research program combines human and animal studies to investigate "where" and how cross-modal learning takes place. The cross-modal learning involves transformation of auditory signals which embed spatial information captured from the environment to visuo-spatial information which is to be processed for navigation in space. The neuroplastic and behavioural changes across various learning occasions with the ultrasonic "Bat Ears" device (www.rs.polyu.edu.hk/batears) will be captured by means of functional magnetic resonance imaging (fMRI). Physiological study would reveal the learning process as to how the auditory inputs ("Bat Ears" signals) trigger the visual responses and how the hippocampal system involves in the process. The results would advance our understanding of how cross-modal learning occurs and the role of existing memory in such process. The knowledge acquired can serve as the theoretical model for facilitating the regain of function in subjects with impaired sensory functions after stroke and brain injuries.

Quantum Order in Novel Materials: Superconductivity and Topological Order
Project Coordinator: Tai-kai Ng (HKUST)

Iron-based (pnictides) superconductors and topological insulators are the most important discoveries in hard condensed matter physics in recent years. The two classes of materials exhibit the common feature of exotic quantum behaviors (quantum order). Elucidating the principles that govern the properties of these materials and exploring their technological implication are the goals of the physics community. The complexity in tackling the many intervening issues in this area calls for a collaborative approach. With the help of a previous Collaborative Research Grant, a research team to tackle this problem is ready. The proposal consolidates the team to study holistically the novel quantum order behind these materials and to explore the nature of general topological order, a key ingredient in quantum information science. Several team members have entered this new field with influential results already produced. The goal of the team is to continue the high-quality research and become internationally recognized.

Study of Microglia and Acute Myeloid Leukemia in Zebrafish
Project Coordinator: Prof Zilong Wen (HKUST)

The human body generates millions of blood cells. These blood cells, which consist of red blood cells and white blood cells, play pivotal roles in numerous physiological processes including the transportation of oxygen and nutrients to the tissues, removal of waste and pathogen, organ formation, and tissue regeneration. Dysregulation of their development and function has been found to cause many human diseases. This collaborative project will investigate the molecular networks governing the development and function of microglia, a brain-resident blood-derived cell, and the onset and progression of myeloid leukemia, a subtype of white blood cell leukemia. The knowledge gained from our research will not only improve our understanding of the molecular basis underlying the development of microglia and myeloid leukemia but also provide new targets for future therapeutic treatments for a variety of relevant human diseases.

Green Slope Engineering for Hong Kong
Project Coordinator: Prof Charles Wang-wai Ng (HKUST)

There has been an increasing demand from the public for environmentally friendly designs and for upgrading of slopes in Hong Kong in recent years. With Hong Kong's rugged topography and frequent rainstorms, landslides have always been an alarming problem. The prime objectives of this project are to investigate and improve our fundamental understanding of root-soil-water interactions and to develop an innovative and environmentally friendly reliability-based preliminary design framework for an "integrated bioengineered live slope cover" for shallow soil slopes in Hong Kong. This live cover will be self-regenerative and sustainable (almost maintenance free). Five major research tasks will be carried out including field monitoring and root system characterization, centrifuge and numerical modeling of bioengineered slopes, development of an integrated quality assurance scheme and a preliminary reliability-based design methodology for bioengineered slopes. Findings from this project will provide new insights into the behavior of bioengineered slopes in Hong Kong and the newly developed innovative reliability-based preliminary design guidelines will provide the basis for future laboratory simulations and field trials.

To Establish a Metabolic Study Center in Hong Kong: Focusing on the Liver-derived Hormones
Project Coordinator: Prof Karen S L Lam (HKU)

Diabetes is a common disease worldwide and its occurrence is rapidly increasing. To develop more effective therapeutic strategies for this disease, the National Institute of Health, USA, has established six national Mouse Metabolic Phenotyping Centers at outstanding academic institutions, to facilitate collaborative research on diabetes. However, although over 10% of the local adults suffer from diabetes, there is no such collaborative research centre in diabetes in Hong Kong or Mainland China. We therefore propose to establish a Regional Metabolic Study Center to support laboratory and clinic-based diabetes research in Hong Kong and Southern China. This Centre will provide standardized methodologies and facilities for metabolic characterization of animal models of diabetes and its related disorders, as well as advance methods for the prediction and diagnosis of these disorders in humans. Employing the expertise and facilities available at this centre, we also plan to identify new methods for the prevention and treatment of diabetes, through research on two hormones secreted predominantly from the liver.

Molecular Pathology of Liver Cancer - a Multidisciplinary Study
Project Coordinator: Prof Irene Oi-lin Ng (HKU)

Liver cancer is a major malignancy worldwide and particularly prevalent in Asia including Hong Kong. Although the risk factors for this cancer are well known, how this cancer forms remain obscure. New strategic treatment modalities for this cancer are much awaited. Knowledge of the molecular and cellular targets underlying the development and progression of liver cancer can help design new treatment modalities for patients.

Development of liver cancer is a multistep process. The two key objectives of our proposal are centered on this theme of multistep hepatocarcinogenesis. The first of the two key objectives is to uncover the genetic and molecular alterations in the hepatitis B virus-associated multistep hepatocarcinogenesis. The role of microRNA in relation to the multi-step hepatocarcinogenesis, cancer metastasis, and liver cancer stem cells will be delineated. Our second key objective is to define the critical events in the wider network of the major Rho/ROCK cell signaling pathway in this multi-step hepatocarcinogenesis, particularly in HCC progression and metastasis.

Our proposed work aims to significantly advance our understanding of the development of liver cancer, which may help design new, effective therapies for liver cancer.

Pluripotent Human Stem Cell Platform for Tissue Regeneration and Drug Screening for Cardiovascular Diseases
Project Coordinator: Prof Hung-fat Tse (HKU)

Although many conventional cardiovascular therapeutic regimens have been proven effective for end-stage heart disease, treatment remains suboptimal due to the limited capacity for cardiac regeneration after injury. Recent advances in the identification of induced pluripotent stem-cells (iPSC) and the biomedical sciences have enabled clinicians and researchers to pursue the revolutionary paradigm of "Regenerative Medicine". Regenerative Medicine involves use of the human body's own stem-cells and growth factors to repair or replace damaged organs or tissues. This project will aim to deliver its objectives in translational medicine by building on a platform encompassing disciplines from discoveries in basic stem-cell biology to preclinical translations and human trials. We propose to generate a human patient-specific iPSC platform established in our team that can serve several purposes: i) novel disease models, ii) drug/cardiotoxicity-screening and iii) a platform to study the basic biology and multipotency of specific cell types, including heart muscle derived from hESC/iPSC.