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Faculty of Medicine, Chinese University of Hong Kong Turning scientific advances into innovative clinical practices

Established in 1981, the Faculty of repair; (3) reproduction, development and Medicine at the Chinese University of endocrinology; (4) stem cell and regen- Hong Kong (CUHK) now has 19 schools eration; and (5) vascular and metabolic and departments, with over 250 aca- biology. With its recent relocation to a new demic staff members. The faculty’s ex- state-of-the-art facility in 2012, the school pertise in cutting-edge translational is reaching new heights of excellence in cancer and genomic research is essen- biomedical research. tial to its mission to improve human The Faculty of Medicine at the CUHK health through scientific advances. has established numerous international ties, winning regional and international he Faculty of Medicine, CUHK has recognition for its work in translational established multiple research cen- genomic research. Highlights of this re- Ttres and institutes with a special fo- search include: cus on translational cancer and genomic research, three examples include: Circulating cell-free nucleic acid • Li Ka Shing Institute of Health Sciences diagnostics (LiHS): A key translational medicine re- The detection of circulating nucleic acids search institute in Hong Kong, the LiHS — DNA and RNA molecules released from opened in 2007 and currently has over 300 the cells of multiple body tissues into the researchers. Its key focus area is transla- blood — provides an opportunity to devel- tional genomics, particularly in the area of op non-invasive blood-based diagnostics non-invasive prenatal testing and cancer. for a variety of conditions. The circulating • Sir Y. K. Pao Cancer Centre: Opened in nucleic acids laboratory at the CUHK, led 1994, the centre is the first dedicated facil- by Dennis Lo and Rossa Chiu, is dedicated ity in Hong Kong for cancer research and to the development of novel molecular clinical services. It houses the State Key diagnostics for the assessment and moni- Laboratory in Oncology in South China, toring of human diseases and pathologies. which focuses on cancers common in Lo and Chiu’s team contributed to the Hong Kong, such as liver, lung and naso- development of non-invasive DNA-based pharyngeal cancers. approaches for the prenatal diagnosis of Both the LiHS and the Sir Y. K. Pao fetal chromosomal and genetic diseases Cancer Centre are located in the Prince of by demonstrating the presence of fetal Wales Hospital, the main teaching hospital DNA in the circulation of pregnant women. of the Faculty of Medicine, CUHK. Together with King’s College Hospital in • School of Biomedical Sciences (SBS): The London and the VU University Medical SBS was created in 2009 through the uni- Centre in the Netherlands, the CUHK fication of the Departments of Anatomy, group pioneered an approach based on Biochemistry (Medicine), Pharmacology massively parallel sequencing of cell-free and Physiology. The 42 professorial staff DNA molecules in maternal blood that is members at the SBS conduct research effective for the detection of fetal Down that falls under five thematic research pro- syndrome. Soon after, the test became grammes: (1) cancer and inflammation; (2) available for clinical use and is now of- neuro-degeneration, -development and fered in over 100 countries. The CUHK

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team was also the first to achieve the direct The project focuses on large-scale determination of the fetal genome through genome-wide analyses to define genetic the analysis of maternal blood, which has events that distinguish tumours from cir- paved the way for non-invasive diagnosis rhosis and progression to metastatic dis- of fetal single-gene diseases. The team ease. Using next-generation sequencing, has collaborated extensively with Charles Wong’s team recently illustrated the muta- Cantor at Sequenom to bring this technol- genic effects of hepatitis B virus (HBV) inte- ogy to the clinic. gration in the development of liver cancer. The CUHK team was also the first to Through transcriptome sequencing, the show that genetic and genomic changes team also demonstrated the presence of of solid cancers can be detected in a viral-human chimeric transcripts from the genome-wide fashion by massively paral- site of genome integrations and helped lel sequencing analysis of cell-free DNA to elucidate the oncogenic effect of viral in blood. This non-invasive molecular insertion. The project has thus provided a scan is able to detect genomic changes foundation for future research into effec- promising disease control strategies for associated with a range of malignancies, tive control strategies for the disease. NPC, Lo’s group has initiated a new project including cancers of the liver, lung, colon, to uncover vital genetic changes through breast and nasopharynx. The team’s work Nasopharyngeal cancer research large-scale whole genome sequencing and has been widely published in high-impact Nasopharyngeal carcinoma (NPC), a dis- bioinformatic analysis. The team plans to journals and has been awarded multiple tinct type of head and neck cancer, is a ma- systematically define the driver mutations, international honours, including election jor healthcare problem in Hong Kong and identify key molecular targets and eluci- to the Royal Society and the US National South China. For the past two decades, date underlying biological mechanisms to Academy of Sciences. a team led by Kwok-Wai Lo, an interna- pinpoint novel biomarkers and therapeutic tional leader in NPC genome research, has targets. The project is expected to contrib- Liver Cancer Genome Project sought to decipher the molecular basis ute to the development of personalized Liver cancer is a highly aggressive cancer of NPC and identify novel targets for this treatment strategies for NPC patients. that is prevalent in China and Southeast deadly disease. The group collaborates Asia. In 2011, Nathalie Wong and her with the Dana-Faber Cancer Institute in Clinical cancer research research team received a HK$45 million the US and the ILCHUN Genomic Medicine The State Key Laboratory of Oncology grant from the Hong Kong Research Grants Institute in South Korea, and works closely in South China is built on the CUHK’s Council to undertake a ‘Liver Cancer with other internationally renowned re- long-established partnership with Sun Genome Project’. The project is a col- search groups. Their pioneering work has Yat-sen University, Guangzhou, in cancer laboration between clinicians and basic provided significant insight into the mo- research, as well as its long tradition of researchers from the CUHK, the University lecular biology of NPC development. cancer research and care in the local of Hong Kong, the Hong Kong University of Recently, Lo and his team discovered community. Led by Anthony TC Chan Science and Technology and the Beijing a novel recurrent transforming fusion and Tony SK Mok, the laboratory has es- Genomics Institute in Shenzhen that aims gene in a subset of patients — the first tablished current standards of care in the to comprehensively delineate whole ge- evidence to support the role of gene rear- management of locoregionally advanced nome and whole-transcriptome somatic rangement in the genesis of NPC. To offer NPC and lung cancer. variations in liver cancer. a molecular basis for the development of Mok’s team focuses on biomarker and molecular targeted therapy in lung cancer. With the discovery of epidermal growth factor receptor mutation, Mok designed and led the IPASS (Iressa Pan-Asia Study), which confirmed the role of this mutation as a predictive biomarker and demonstrat- ed the superiority of targeted monothera- py over doublet chemotherapy. Mok has also led a number of other multinational clinical trials that have contributed to the current standard of practice for the man- agement of advanced-stage lung cancer. Focusing on locoregionally advanced NPC, Chan and his team reported the first prospective randomized study in one

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endemic area to establish concurrent cis- platin-radiotherapy as the current standard Discovered at the CUHK of care. Collaborating with Cancer Research →→ Dennis Lo and Rossa Chiu noninvasively determined the fetal genome, UK, they developed a therapeutic Epstein- DNA methylome and transcriptome through maternal blood analysis. Barr virus (EBV) vaccine to boost in vivo →→ Nathalie Wong identified a novel mechanism of viral-host fusion sequence T cell responses to EBV proteins expressed HBx-LINE1 in liver oncogenesis. by tumour cells. The pilot study established KW Lo generated a high-resolution genome map of EBV-associated naso- the safety and immunogenicity of the EBV →→ pharyngeal cancer. vaccine. A multinational phase 2 efficacy Anthony Chan and Tony Mok led international multi-centre anti-PDL1 im- study is ongoing. →→ munotherapeutic studies in nasopharyngeal and lung cancers.

Digestive diseases and gastrointesti- →→ Jun Yu discovered novel molecular events and biomarkers of gastrointesti- nal cancer through genome sequencing and bio-functional analyses. nal cancer studies The Institute of Digestive Disease (IDD), →→ HC Chan discovered a novel role of cystic fibrosis transmembrance conduc- tance regulator in insulin secretion and cystic fibrosis-related diabetes. established in 2006 by Joseph JY Sung, seeks to improve the diagnosis and treatment of digestive diseases through 1,600 publications, 300 were published Biology Research Centre (ECBRC) in China, basic, translational and clinical research. in high-impact journals. with help and support from the National Comprising a multidisciplinary group of The IDD has been honoured with 42 Natural Science Foundation of China. investigators from a wide range of inter- prestigious national and international Since its establishment, the ECBRC nationally recognized academic fields, awards. Core IDD team members serve has built a multidisciplinary technology IDD’s ultimate goal is to improve patient on editorial boards of major medical platform and has stayed at the forefront survival through the early detection and journals and advisory boards of major of epithelial cell biology research. This treatment of gastrointestinal cancers. industrial partners and have secured 120 cross-disciplinary approach, together with The IDD has made a number of im- external local, national and international a network of over 50 collaborating labo- portant discoveries related to the treat- research grants of over HK$350 million in ratories worldwide, have led to ECBRC’s ment of digestive diseases, including a the past 5 years. high-impact publications in leading jour- technique for the management of peptic In addition, The State Key Laboratory nals, such as Nature Medicine. Among the ulcer bleeding, led by Francis KL Chan, of Digestive Disease was established at ECBRC’s many notable discoveries, ECBRC and insight into the treatment of HBV the IDD in 2013, in partnership with the researchers have identified the role of infection, led by Henry LY Chan. In addi- Fourth Military Medical University in main- epithelial ion channels in reproduction, tion, the research laboratory led by Jun land China. The IDD’s strong international mechano-sensing, cancer development Yu has pioneered the use of microRNAs network, enables collaborations with key and insulin secretion, and have illustrated as novel non-invasive biomarkers for leaders in the field around the world. the importance of defensins in sperm colorectal cancer, and has discovered function and male fertility. novel tumour suppressor genes in gastric Epithelial cell biology research With a strong team led by Hsiao Chang cancer and new mutation signatures in Epithelial cells form a diverse group of Chan, the ECBRC is engaged in a wide colorectal and gastric cancers. The IDD’s tissues that cover or line almost all body variety of basic and translational research. research has been published in a number surfaces, cavities and tubes, such as the From investigation of the ion channels of international peer-reviewed journals, lungs, liver, kidneys and reproductive in signal transduction to researching risk including the New England Journal of tract. Defects in epithelial cell function factors of assisted reproduction technol- Medicine and The Lancet. Of IDD’s over are therefore associated with a wide spec- ogy, the ECBRC’s research has numerous trum of disorders and diseases, including potential applications in the diagnosis and hypertension, diabetes, infertility and treatment of infertility and other diseases. cancer. Recognizing the importance of The ECBRC embraces the team spirit and epithelial cells, researchers at the CUHK is open to further collaborations, including and the Academy of Military Medical joint ventures with the industrial sector to Sciences joined forces in 1999 to estab- promote translational research. “Together, lish the first and leading Epithelial Cell great things are possible,” Chan says. Contact Email: [email protected] Tel: 852-2632-3799 Fax: 852-2649-0208 Web: www.med.cuhk.edu.hk/eng

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