Project Title: Centre for Medical Engineering of Molecular and Biological Probes
Project Coordinator: Prof Nathalie Wong (CUHK)
Abstract
Cell-surface proteins are the primary route of cell-cell and cell-environment communication, and an integral class of proteins that tightly regulates numerous cellular processes and vital signalling. Although membrane proteins represent only ~23% of the human proteome, over 60% of current FDA-approved drugs are directed against them. Despite their clinical appeal, cell-surface proteins are underrepresented in public proteome and genome databases. In this Project, we propose to conduct a systematic analysis for focused discoveries of cell-surface neo-epitopes in cancers widely found in Asia: hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC) and lung adenocarcinoma (LADC). We will leverage the information for generating dual-targeted theranostic probes for molecular imaging and precision therapy. We will also exploit characteristic features of cell-surface antigens for engineering genetically modified CAR T-cells.
To achieve our goals, we have assembled a multidisciplinary team of strong investigators. Our team members have previously made important discoveries on the causal events of HCC, NPC and LADC, yet establishing many of these somatic changes in tailored therapy remains a challenge due to the limited number of approved drugs in targeting genetic vulnerabilities. Our recent sequencing work has revealed a window for theranostics development by directing probes against tumor-specific cell-surface proteins. We have obtained evidence from SMRT sequencing to show that neojunctions derived from Alternative Splicing are vastly more common than somatic mutations, and many involved cell-surface receptors. This new knowledge has invigorated our pursuit of more promising treatment options and inspired the current application. Our team members have also made significant contributions in cell-SELEX screening for nucleic acid aptamers and characterized surface proteins for antigen-binding fragment in CAR T-cells engineering. We have successfully licensed diagnostic assays and founded biotech companies in Hong Kong. Furthermore, our clinical investigators are all frontline clinicians and leaders in international clinical trials. This project will build on existing strengths, in terms of our track record in cancer genome and EBV research, bioinformatics, aptamer chemistry, small molecule synthesis, CAR engineering, clinical expertise in oncology, as well as unique study models and infra-structure facilities that we have collectively acquired over the years. The establishment of a ‘Centre’ for theranostics engineering under the aegis of the AoE scheme will have strategic importance for Hong Kong. The numerous applications of theranostics engineering in the fields of biotechnology and biomedicine will bring economic benefits, societal impact and fresh thinking, heightening the international stature of Hong Kong as a leading centre of excellence.
Project Title: Aging, Skeletal Degeneration and Regeneration
Project Coordinator: Prof Ling Qin (CUHK)
Abstract
The world population is aging. The Hong Kong Government has projected our local population with a rapid increase in aging population from 15% in 2014 to 36% in 2064. The life expectancy of both female and male Hong Kong Chinese ranks No. 1 in the world recently. Incidence of age-associated osteoporosis and bone fractures are high, with one osteoporotic fracture occurring every three seconds worldwide. The associated high mortality rate imposes a huge socio-economic and financial burden to the patients, families，and society. Our mission focuses on clinical translation by providing innovative and effective treatment for age-associated musculoskeletal disorders. Extensive research has been conducted on aging, coordinated and multidisciplinary research facilitating skeletal regeneration in bone metabolic disorders and fragility injuries, especially in searching for bioactive and biodegradable implantable materials for temporal fixation and stimulating skeletal regeneration, are still highly desirable. We recently identified the unique function of neuronal protein regulating the regeneration of skeletons via sensory nerves (Zhang Y. et al., Nat Med, 2016 [1]; highlighted as an important milestone in biodegradable metals by Nat Rev Rheumatol and World Biomaterial Society). Our collaborative achievements include identifying the unique biomechanical and biological function of biodegradable metals, especially Magnesium (Mg) as revolutionary biometal (Zheng YF, Qin L, Yang K, 2016, Monograph: Biodegradable Metals [2], and Wang JL et al. Advanced Science, 2020 [3]). Degradation of Mg releases Mg ions and hydrogen gas and creates a local alkaline environment. We have delineated that Mg ions stimulate sensory nerve endings in the periosteum and upregulate and release of calcitonin gene-related peptide (CGRP) from dorsal root ganglions. CGRP, an osteogenic neurotransmitter, facilitates differentiation of periosteum-derived stem cell into osteoblast linage, and thus benefit osteoporotic fracture repair, highlighting Mg as an excellent candidate for facilitating skeletal regeneration in elderlies. The alkaline environment and hydrogen gas may also contribute to new bone formation via regulating local inflammation, reducing oxidative stress, and attenuating cell senescence. However, the underlying mechanisms are not well defined. For this AoE proposal, our multidisciplinary team will apply advanced biotechnologies to address these scientific questions while continuing our translational work supported by our previous GRF/ITF/CRF/TRS on innovative biodegradable implants towards multi-centre clinical trials and Class III medical product registration for broadening clinical applications. Our collective efforts will enhance the regeneration of challenging musculoskeletal disorders and hence reduce our healthcare and socio-economic burden of our aging society.
Key References (*: Corresponding author)
- Zhang Y, Xu JK, Ruan YC, Yu MK, O'Laughlin M, Wise H, Chen D, Tian L, Shi D, Wang JL, Chen S, Feng JQ, Chow DH, Xie X, Zheng L, Huang L, Huang S, Leung K, Lu N, Zhao L, Li H, Zhao D, Guo X, Chan K, Witte F, Chan HC, Zheng Y*, Qin L*. Implant-derived magnesium induces local neuronal production of CGRP to improve bone fracture healing in rats. Nat Med 22: 1160-1169, 2016.
- 鄭玉峰，秦嶺，楊柯. 2016. 可降解金屬. 科學出版社, 2016.
- Wang JL*, Xu JK, Hopkins C, Chow DH, Qin L*. Biodegradable Magnesium-Based Implants in Orthopedics-A General Review and Perspectives. Adv Sci (Weinh) 7(8): 1902443, 2020.
Project Title: Meta-optics, Meta-acoustics and Meta-devices
Project Coordinator: Prof Din-ping Tsai (PolyU)
Abstract
We aim at developing novel meta-materials and meta-devices that can control and manipulate electromagnetic and acoustic waves for improving the quality of human daily life. Metamaterials and meta-devices take advantages of the localized and non-localized resonances of artificial structures in which the response of the electrons, phonons, plasmons, and excitons are strongly modified to give novel properties and functionalities which are not found in nature. Our project will cover the design, numerical simulation, advanced manufacturing, characterizations and measurements of these materials for various applications including environment, biomedical, imaging and sensing, and information security. We expect that this AoE project will generate a new platform for knowledge-based intelligent artificial materials and devices which are low energy consumption (“green”) and compatible with advanced manufacture 4.0 in micro- and nano-electronics industrial techniques for wearable or portable innovation. We trust that local impact and global excellence will be fully demonstrated by the results of this AoE project. The existing world-renowned research strength of different local universities will be assembled and propelled to a higher level by this strategic project. Local young talents will be incubated, and global talents will be attracted to Hong Kong. The intellectual properties and innovations of meta-devices in this project will be transferred to the local industries and business sectors. The upstream knowledge and intellectual properties can strategically transform and upgrade Hong Kong’s high-technical industries and business sectors. Hong Kong is currently unique in having a critical mass of metamaterial scientists, capable of making fundamental discoveries and deliver to the real world applications and benefiting business and industries in the Greater Bay Area.
Project Title: 2D Materials Research: Fundamentals Towards Emerging Technologies
Project Coordinator: Prof Wang Yao (HKU)
The rapid development of information technology has been based on the continuous scaling down of microelectronic devices that improves cost, performance and power. This trend, empirically summarized as Moore's law, is coming to an end because of the intrinsic scale limit of silicon microelectronics. The new era of innovation will be profoundly different, calling for: new material systems to host even smaller devices under new geometry, new heterogeneity, new quantum degrees of freedom to carry information, and new physical principles to process and store information.
Two-dimensional (2D) materials have a great potential to revolutionize microelectronics and information technology. The variety of 2D materials feature a wide range of material properties from metal, semiconductors, insulators to magnets and superconductors, as well as exotic physics associated with electrons’ quantum degrees of freedom (spin & valley) that could be exploited to encode and process information more efficiently. Their tiny thickness - just a few atoms at most - promises the ultimate miniaturization of devices, and unparalleled control of materials and device functions. Moreover, 2D materials feature an unprecedented flexibility in their assembly into heterostructures, through which new materials and device functionalities may emerge. This project aims to explore these exciting opportunities for revolutionizing electronics, optoelectronics and photonics, through a concerted effort addressing the fundamental issues from physics, materials synthesis to device engineering based on 2D materials.
Led by pioneers in the field of 2D materials, this AoE project is an inter-institutional (involving 5 universities) and interdisciplinary one covering physics, applied physics, chemistry, electrical engineering. The team will seek to sustain Hong Kong’s edge in the field through basic and applied research, with a long-term goal of developing new prototype devices that will have application and commercialization potentials for Hong Kong.