enLIGHTen Issue 1 by Lee Kong Chian School of Medicine

Edition 1 • 2019

LKCMedicine

en Light en The Promise of

Regenerative Medicine Medical education meets IR4.0 at inaugural Transform MedEd Colouring Gray’s Anatomy

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Are we entering an age of super-physicians? LKCMedicine’s Class of 2018 Graduates

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LKCMedicine

en Light en Editorial Team Advisor Professor James Best Editor-in-Chief Siti Rohanah Koid Editor Nicole Lim

The Lee Kong Chian School of Medicine, a partnership between Nanyang Technological University, Singapore (NTU Singapore) and Imperial College London (Imperial), is training doctors who put patients at the centre of their exemplary care. The School, which offers both undergraduate and graduate programmes, is named after local philanthropist Tan Sri Dato Lee Kong Chian. Officially opened on 28 August 2017 by Singapore’s Deputy Prime Minister Mr Teo Chee Hean, LKCMedicine aims to be a model for innovative medical education and a centre for transformative research. The School’s primary clinical partner is the National Healthcare Group, a leader in public healthcare recognised for the quality of its medical expertise, facilities and teaching. Graduates of the five-year undergraduate medical degree programme that started in 2013 will have a strong understanding of the scientific basis of medicine, with an emphasis on technology, data science and the humanities. The School’s first batch of doctors graduated in 2018 with Bachelor of Medicine and Bachelor of Surgery (MBBS) degrees awarded jointly by NTU Singapore and Imperial.

Contributors & Writers Nicole Lim Sean Firoz Chan Weiliang Anne Loh Sze Miang Amanda Lee Andy Kwan Chew Sien Sufian Bin Suderman Woon Yong Sheng Eugene Andrew Czyzewski Cayden Pang Ong Hong Xi Rueben Sng Lim Qiu Li Editorial Board Professor James Best Professor Michael Ferenczi Professor Phillip Ingham FRS Associate Professor Tham Kum Ying Dr Vivien Chiong Andrew Scheuber Siti Rohanah Koid Suzanne Lim Designer Tan Yoke Hwee Illustrator Andrea Loh

Cover photo: Human Embryonic Stem Cell-derived Vascularised Kidney Organoid. A miniature human kidney generated from human embryonic stem cells using directional differentiation in a dish. This complex multi-cellular organoid contains glomerulus (in green), tubules (in blue), and blood vessels (in red). Acknowledgement: Low Jian Hui, LKCMedicine PhD student, Xia Yun Lab

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Content ENGAGE

DISCOVER

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The Dean shares his vision and direction

From The Dean

GET WIRED News from LKCMedicine

What’s in focus at LKCMedicine

The promise of regenerative medicine Wounds that won’t heal

THINK

Our experts get you thinking

22 24

Are we entering an age of super-physicians? For better or for worse?

A busy year ahead for first Chair Professor in Neuroscience

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New dimensions to fight diabetes Battling chronic diseases with research

TOAST

Our achievements at a glance

SNAP

Capturing our most significant milestones

Medical education meets IR4.0 at inaugural Transform MedEd

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The gift of the year

PARTNER

Spiky mini contact lens heralds future of glaucoma treatment

New 3D-printed anatomical models boost anatomy teaching

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New initiative helps Singaporeans breathe easier

Experts gather to kick-start regional efforts to curb antimicrobial resistance

LKCMedicine students screen more than 600 elderly residents in new health screening initiative

Landmark population health study recruits 1,000th participant

In the pipeline, with our main partners

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Meeting IR 4.0 head(set) on

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LKCMedicine’s Class of 2018 Graduates Reflections of a new graduate

What they say

PROFILE

Meet our faculty, staff and students

Wang Xiaomeng: eyeing diseases through blood vessel formation

Leading the dementia fightback: In conversation with Paul Matthews

Becoming a Clinician Scientist

REVIEW

Select review of our impactful research publications

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Nipping cancer in the bud

Answering the call to war against diabetes

Colouring Gray’s Anatomy enlighten ed. 1

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ENGAGE

From the Dean / Professor James Best Welcome to the inaugural issue of enLIGHTen! The Lee Kong Chian School of Medicine (LKCMedicine), a partnership between Nanyang Technological University, Singapore and Imperial College London, has achieved a major milestone in 2018. Our pioneer batch of students, who joined in 2013, graduated in July last year and are now working in hospitals across Singapore, caring for fellow Singaporeans. We are confident that they are executing well their promises to provide exemplary patient-centred healthcare. I am pleased to share their and our journey in this first issue of our annual magazine, which captures key highlights from the School over the past year in the form of feature stories, opinion pieces by faculty members, in-depth profiles and human-interest stories about research, medical education, and wider issues relating to the healthcare and biomedical research sectors. Since its inception in 2010, LKCMedicine has grown in size and stature. To train future doctors, we have created an innovative curriculum, with an interdisciplinary learning and research environment that nurtures our students to be wellgrounded in science, patient-centred in approach, and team-based in practice. Many aspects of our innovative curriculum have become the Schoolâ&#x20AC;&#x2122;s hallmarks that others have sought to learn from, such as the intensive use of technology enhanced team-based learning, simulation, early patient contact, and a studentcentred pedagogy. In this issue, we profile the innovative work of one of our faculty members, who is making waves in the medical education research landscape with his 3D-printed creations of anatomical specimens to enhance the teaching of anatomy.

Professor James Best is Dean of Lee Kong Chian School of Medicine and is an internationally renowned academic leader.

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OneLKC community celebrating milestones together

An equally important pillar of LKCMedicine is our dedication to research. Our strategy emphasises the five domains of Lifespan Medicine, Population Health, Medical Biology, Medical Engineering and Medical Education Research, underpinned by our programmes in Cardiorespiratory and Metabolic Health, Infectious Diseases, Neuroscience and Mental Health, Population Health and Health Services Research, Systems Biology, Regenerative Medicine and Developmental Biology, Medical Education Research as well as Health Technologies, Nanomedicine and Bioengineering — areas closely linked with Singapore’s health challenges — particularly in caring for its rapidly ageing population. In this issue, we look at the rapidly progressing field of Regenerative Medicine, studying its origins, development and the involvement of our researchers, including those working in collaboration with our parent universities NTU Singapore and Imperial College London. As you will read in this issue, we have received generous funding from philanthropic organisations to extend our research and support our students. Last year, the School received with heartfelt thanks $11 million from the Irene Tan Liang Kheng estate, launched by the late philanthropic couple Madam Tan and Mr Ong Tiong Tat. With a matching grant from the government, the gift will see the School making further inroads in diabetes and neuroscience research, for which we have initiated chair professorships. Our vision at LKCMedicine is to redefine medicine and transform healthcare. This magazine will enlighten you on how the LKCMedicine team is striving to live up to the challenge.

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Prof Subra Suresh giving his welcome address

Prof Simone Buitendijk addressing delegates on the first day

Medical education meets IR4.0 at inaugural Transform MedEd Co-chairs Prof Naomi Low-Beer and Mr Martin Lupton welcoming delegates

Anne Loh Assistant Director Communications & Outreach

rom smart t-shirts and holograms to 3D-printed human organs and artificial intelligence (AI), the reality of healthcare is fast catching up with science fiction. The unprecedented rate of change poses novel challenges to medical educators who have to prepare students for an ever-changing workplace environment, without losing sight of the uniquely human needs of the patients at the heart of it. This was the focus of discussions during the inaugural Transform MedEd Conference, jointly organised by LKCMedicine and Imperial College School of Medicine. With a programme packed with plenaries, symposia, short communications and workshops, discussions focusing on harnessing the latest pedagogies in medical teaching, including AI, AR and VR-enhanced simulations and gamification, attracted strong interest from conference participants. The conference was aptly hosted by LKCMedicine, a young and dynamic medical school known for its latest approach to teaching - from technology-enhanced team-based learning to the use of virtual dissection and 3D-printed specimens in anatomy teaching. Addressing the close to 400 delegates from 15 countries during the opening of the conference, NTU President and Distinguished University Professor Subra Suresh said in his welcome address, “We have an opportunity to transform healthcare – by choice or not – we should not let opportunities that come about because of crises or disruption go to waste, as Rahm Emanuel famously said. We may not get definite answers at this conference but we can start the conversation.” But while technology might change the face of medicine, we cannot lose sight of patient-centred, empathetic, compassionate care, Prof Subra stressed, setting the tone for the two-day long conference held at LKCMedicine’s Clinical Sciences Building last November. Sitting at the crossroads of change and technology, the medical textbook, long a cornerstone of medical education, is one area ripe for disruption. In her keynote address, Dame Professor Parveen Kumar, co-author of Clinical Medicine, said,

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“Medical knowledge will double every 73 days by 2020. Online textbooks are now interactive, so it’s important to have one with curated content by experts. After that, you can take it further however you want to.” A combination of traditional and new teaching methods – coined ‘blended learning’ – is needed to deal with this transformation in education, said the Professor of Medicine and Education at the Barts and London School of Medicine and Dentistry, Queen Mary University of London.

Shades of reality

The challenge of helping medical students to understand the complex 3D structures of human anatomy as well as learning the skills needed for practical situations was addressed during the short communication session on Immersive Learning in Medical Education chaired by LKCMedicine Associate Professor of Medical Education and Acting Director for Medical Education Research & Scholarship Unit, Nabil Zary. In this session, the potential use

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of technologies like the Hololens, AR, VR and mobile apps was explored. Associate Professor of Developmental Biology at Leiden University Medical Centre Beerend Hierck, and Clinical Senior Lecturer in Colorectal Surgery at Imperial Dr James Kinross, each showcased the use of the Hololens as an immersive and interactive learning tool. With this tool and a purpose-built app, it is possible to learn anatomy from your own body, according to A/Prof Hierck. With his Dynamicanatomy app, students can be fully immersed in and interact with fellow students while studying the ankle joint.

operandi of medical education and disrupting healthcare, the symposium Artificial Intelligence in Medical Education was well-received. Speakers included Imperial Digital Learning Hub Director Gideon Shimshon, who discussed how the teacherstudent interaction can be rethought through AI-enabled feedback and grading, while Dean of Morling Education and Professor at the Australia’s University of Divinity James Dalziel spoke about the opportunities brought about when AI is incorporated into learning design. While AI may offer great new opportunities to innovate learning, Dr Melvin Chen, a lecturer in philosophy and medical AI researcher at NTU’s School of Humanities, discussed the inherent care deficit in AI.

Poster presentations take place in the Auditorium foyer

And yet, patients must come first

“We have an opportunity to transform healthcare – by choice or not – we should not let opportunities that come about because of crises or disruption go to waste, as Rahm Emanuel famously said. We may not get definite answers at this conference but we can start the conversation.” - Professor Subra Suresh

IR 4.0 is set to usher in many technological benefits: busting frontiers in research, bringing healthcare to inaccessible parts of the world or aftercare into the home, predicting probability of health risk or epidemics, monitoring health through wearables and remote diagnosis. With such transformations, many are concerned whether AI will one day replace the healthcare workers at our bedside, and take over research labs and hospitals. Professor Dato Dr Adeeba Kamarulzaman, Dean of Universiti Malaya’s Faculty of Medicine, The LKCMedicine booth with 3D-printed speaking during the panel discussion on human organs Transforming Healthcare Through Our Graduates, summed up the challenge, saying, “We will find as we use more technology, patients will expect more of doctor-patient relationships.”

Closing on a high note Dr Kinross’ presentation on AR for the Intra-operative Visualisation of Anatomy and Tumour Regression in Rectal Cancer using the Hololens platform addressed the need to help students simulate practical situations. AR is fully three-dimensional and multiple students can learn together as they walk around and interact with the hologram. In addition to technologies like the Hololens, VR also provides opportunities to create immersive learning tools. Presenting a VR simulator for total hip replacement surgery, Clinical Research Fellow Mr Kartik Logishetty, from the Imperial College Faculty of Medicine’s Department of Surgery & Cancer, demonstrated how the operation could be simulated in an operating theatre scenario before a surgeon undertakes it.

Non-carbon intelligence

With artificial intelligence and the fourth Industrial Revolution (IR 4.0) poised to challenge the standard modus

Fully appreciative of the sheer amount of knowledge exchanged and shared over the two-day conference, conference co-chair LKCMedicine Vice-Dean for Education, Professor Naomi Low-Beer, said in her closing remarks, “This conference was a bigger success than we had imagined with 393 registrations from 15 countries, one keynote, four plenaries, four symposia, 10 workshops; and 104 submitted abstracts with 54 selected for poster and 35 for oral presentations. Thank you to all who worked on this over the past year.” Fellow co-chair and Imperial Faculty of Medicine Vice-Dean for Education Mr Martin Lupton added, “Collaboration between Imperial and NTU has led to profound improvements in medical education at both Imperial’s School of Medicine and LKCMedicine. Advances in technology, pedagogy and practice have enabled this transformation. Our common ambition to push the boundaries of medical education catalysed this conference.” Imperial Vice-Provost (Education) Professor Simone Buitendijk who had given the welcome address as well as presented at the Transforming Healthcare panel discussion, summed up her experience at Transform MedEd, “It was wonderful to attend such an exciting gathering of innovators in medical education who are all keen to evidence their interventions and make sure we give our students the quality education they deserve. From virtual reality in the classroom, to community engagement and novel forms of authentic assessment, all the topics were extremely relevant.” The next edition of Transform MedEd will be held in March 2020 in London. enlighten ed. 1

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Trustee of the Irene Tan Liang Kheng Estate Mr Tan Hsuan Heng (centre) with (left to right) Dean of LKCMedicine Prof James Best, Governing Board Chairman Mr Lim Chuan Poh, NTU President Prof Subra Suresh and VP (Advancement and Alumni) Prof Alan Chan

The gift of the year Anne Loh Assistant Director Communications & Outreach

was a mere chance encounter over a plate of char kway teow that led to a deep friendship between lawyer Mr Koh Choon Joo and investment trader Mr Ong Tiong Tat and his wife, Madam Irene Tan Liang Kheng. Their friendship would last more than 40 years and its benefits would stretch well beyond the three people at its heart. Between them, the three active philanthropists, who shared a passion for education, bequeathed millions to various causes during their lifetime. Last August, the Lee Kong Chian School of Medicine (LKCMedicine) was the beneficiary of an $11 million gift from the Estate of Madam Tan. With government matching, the total endowment rose to $22 million, to fund medical education and healthcare research. Trustee of the Irene Tan Liang Kheng Estate Mr Tan Hsuan Heng said, “My aunt and uncle, Irene Tan Liang Kheng and Ong Tiong Tat, strongly believed in the value of education and have always chosen to support this worthy cause.” “With a new medical school, there are more opportunities. A new school provides an opportunity to develop a curriculum based on other schools’ experiences and shortcomings and enables it to work towards being the best in class in a short timeframe,” he added. The donation came from the sale in 2017 of a large bungalow sitting on premium Singapore land at 16 King Albert Park, a good class bungalow bequeathed to Mr Ong by Mr Koh who passed away aged 96 in 1997. After Mr Koh’s death, Mr Ong, as executor of Mr Koh’s Estate, continued their shared legacy by disbursing more than $16 million to various educational institutions, in particular the National Institute of Education, NTU Traditional Chinese Medicine, NUS CJ Koh Law Library, NUS Law, Raffles Institution, Hwa Chong Institution, CHIJ Secondary Toa Payoh, Nanyang Polytechnic, etc . Even though Mr Ong and Madam Tan were diagnosed with Stage 4 stomach

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Prof James Best addressing the audience of esteemed guests, faculty and staff on the significance of this gift and its impact on LKCMedicine in areas of medical education and research

cancer and Stage 4 pancreatic cancer respectively in 2010, both continued to give generously to worthy causes. Their belief was that they could make no better investment to nurture young people than by increasing their access to education, said Mr Tan. “They expanded CJ Koh’s values and belief in elevating the under-privileged through access to education,” added Mr

scholarship that will cover all five years of the LKCMedicine MBBS programme and will be awarded to students from the 2019 intake onwards. Two chair professorships were also created: the Irene Tan Liang Kheng Chair Professorship in Neuroscience and the Ong Tiong Tat Chair Professorship in Diabetes Research. A million dollars was also set aside to support the development of serious games to be administered and disbursed by the gAmes for HeaLth InnoVations CentrE (ALIVE) over the next five years for research. At the signing ceremony, the School announced the inaugural appointment of LKCMedicine Professor of Neuroscience and Mental Health George Augustine to the Irene Tan Liang Kheng Chair Professorship in Neuroscience. The chair professorship boosts LKCMedicine’s research ambitions into neurodegenerative and psychiatric disorders, such as dementia as Singapore’s population is rapidly ageing. “LKCMedicine, as a world-class medical school, places LKCMedicine Professor in Metabolic great importance on research as well as education. Medicine and Principal Investigator in We strive to transform healthcare through excellent its Immuno-Metabolism Laboratory Bernhard Boehm was appointed to the translational research and this funding for two of our major Ong Tiong Tat Chair Professorship in research areas will significantly extend our capability.” Diabetes Research in January 2019. Diabetes and other metabolic - Professor James Best disorders are also important research areas for LKCMedicine. This is in line with the Singapore government’s call for a Tan, whose uncle and aunt passed away war on diabetes, given that one in nine Singaporeans lives with the condition while in 2013 and 2016 respectively. one in three has a lifetime risk of getting it. The Ministry of Health projected that the On 13 August 2018, NTU President number of Singaporeans with diabetes will reach a million by 2050. and Distinguished University Professor “I wish the professorships in neuroscience and diabetes will contribute to Subra Suresh received the ceremonial formidable areas of research which will improve the lives of the elderly in Singapore cheque for $11 million from Mr Tan at and around the world, thereby raising the standing of LKCMedicine,” said Mr Tan. a signing and unveiling ceremony of Expressing the university’s appreciation of the gift, Prof Suresh said, “NTU LKCMedicine’s Ong Tiong Tat & Irene deeply appreciates this gift from the Estate of Irene Tan Liang Kheng which will go Tan Liang Kheng Auditorium at the towards research and education. This is an investment in the future of young minds Clinical Sciences Building in Novena and the betterment of the human condition that will see ever-growing returns for the which has been named in honour of the state of humanity for years to come.” late philanthropic couple. LKCMedicine Dean Professor James Best added, “LKCMedicine, as a worldThe gift funds a new Irene Tan class medical school, places great importance on research as well as education. Liang Kheng Scholarship for needy We strive to transform healthcare through excellent translational research and this Singaporean undergraduate students, funding for two of our major research areas will significantly extend our capability.” adding to the six scholarships and Just three months after LKCMedicine received this generous gift, Mr Tan made three bursaries that the medical a second donation, this time to the university’s teaching community, donating $4 school already offers, thus ensuring million to help fund NTU’s development of teachers. that deserving students can answer Turn to pages 34 and 35 to get to know more about the first Irene Tan Liang Kheng Chair Professor the medical calling regardless of their in Neuroscience and the first Ong Tiong Tat Chair Professor in Diabetes Research. financial circumstances. This is a full enlighten ed. 1

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LKCMedicine in the news…

The microneedles on the eye patch can be loaded with drugs. Worn like contact lenses, the patch is painless and minimally invasive. The drug is released slowly as the biodegradable microneedles dissolve in the corneal tissue

(L-R) Assistant Professor Wang Xiaomeng from Lee Kong Chian School of Medicine and Professor Chen Peng from the NTU School of Chemical and Biomedical Engineering are part of an NTU team that developed a ‘contact lens’ eye patch to treat eye diseases. Painless and minimally invasive, the patch could potentially be a viable alternative to the current treatment options, which face poor patient compliance

Spiky mini contact lens heralds future of glaucoma treatment

cientists at NTU have developed a 2mm square contact lens-like patch that delivers drugs directly into the eyeball via biodegradable microneedles. This could transform the way many common eye conditions, such as glaucoma and macular degeneration, will be treated. The team was led by NTU School of Chemical & Biomedical Engineering (SCBE) Professor Chen Peng, Assistant Professor Xu Chenjie and LKCMedicine Assistant Professor Wang Xiaomeng. Eye drops, while widely used, are known to be an ineffective way to deliver medication to the eye as they cannot easily penetrate the natural barrier and are often washed away by blinking or tears. Eye injections, which deliver medication straight into the eyeball, on the other hand, are painful and carry a risk of infection and damage.

The patch combines the painlessness of eye drops with the effectiveness of an injection. It is applied much like a contact lens by gently pressing onto the eye. The drugcontaining microneedles detach from the patch and remain in the cornea, releasing gradually the drug as they dissolve. In a proof-of-concept study in mice published in Nature Communications in November 2018, a single application of the patch was 90 per cent more effective in alleviating corneal neovascularisation, which is common among contact lens wearers and can lead to blindness. This is compared with a single eye drop which contains 10 times the dosage of drug used in the patch. Turn to page 30 to get to know LKCMedicine Assistant Professor Wang Xiaomeng and her work on curbing unwanted blood vessel growth. Photos: NTU Singapore

New 3D-printed anatomical models boost anatomy teaching

edical students at LKCMedicine now benefit from even more hands-on time with anatomical specimens, thanks to the introduction of a novel teaching resource. Complementing the School’s extensive range of donated human bodies and body parts, these 3D-printed replicas create an affordable and accessible source of anatomically correct specimens that mimic the touch and feel of human tissues. In addition, different structures such as muscles, nerves or blood vessels, are colour coded to support students who are new to anatomy. The first 3D-printed models were used as a supplementary teaching resource in the Year 1 curriculum last year. The project is a collaboration between LKCMedicine Head of Anatomy Assistant Professor Sreenivasulu Reddy

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Mogali and NTU’s Singapore Centre for 3D Printing. After CT scanning the human specimens, each structure is labelled, assigned a colour and material mix. Unlike powder-based 3D-printed models, these multi-material models are flexible, allowing students to explore underlying structures without fear of causing damage. And even if a specimen is damaged, it can be reprinted easily and quickly. An added advantage of 3D printing technology is that larger body parts, such as the upper and lower limb, can be printed in easy-to-handle sections, such as the shoulder, elbow, and hand and wrist.

The 3D-printed human heart with its four chambers, coronary arteries and nerve system allows students to study the cardiovascular system

Turn to page 32 to find out how LKCMedicine Head of Anatomy Assistant Professor Sreenivasulu Reddy Mogali came up with this idea and what drives him to deliver an engaging, interactive and modern anatomy learning experience.

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New initiative helps Singaporeans breathe easier

ne in three Singaporeans with smoker’s lung is actually a non-smoker. To understand this and other lung conditions, LKCMedicine launched the Academic Respiratory Initiative for Pulmonary Health (TARIPH) in March 2018. TARIPH, which is led by LKCMedicine academic co-leads Assistant Professor of Molecular Medicine Sanjay Chotirmall and Associate Professor of Exercise Physiology Fabian Lim, aims to understand the unique characteristics of lung diseases in Singapore, a timely effort as lung diseases are expected to rise in tandem with an ageing population and worsening environmental pollution. TARIPH also brings multidisciplinary partners together, including local academic and healthcare institutions like the National University of Singapore, the Institute of Molecular and Cell Biology, A*STAR and all major hospitals in Singapore, as well as international academic institutions such as the University of Newcastle and the University of British Columbia. Summing up the need for an initiative like TARIPH, A/Prof Lim said, “We must understand why Asian respiratory disease is different, and dedicated research is the optimal way to do this.” Among the early achievements of the group are four publications in worldrenowned journals such as Respirology, laying the groundwork for future clinical studies. As part of the group’s plans to bring TARIPH to the front line of respiratory care, the first-ever TARIPH Asthma workshop, titled Asthma in Singapore: Clinical and Research Needs, was held in August 2018. The workshop brought together various stakeholders from healthcare clusters and academic institutions to discuss better ways to deliver asthma care to patients. In addition, TARIPH members have embarked on research collaborations with several major hospitals to develop better detection for bronchiectasis and COPD and to investigate the airway microbiome in patients with lung cancer. Asst Prof Chotirmall said, “TARIPH will only be successful if we create this open inter-disciplinary collaborative platform, where all are willing to exchange ideas with the aim of helping patients.”

Speakers at the special TARIPH session are united in the effort to better understand lung disease in Singapore

Multidisciplinary partners discuss better ways to deliver asthma care to patients

Experts gather to kick-start regional efforts to curb antimicrobial resistance

Infectious disease experts convene at LKCMedicine to discuss the challenges facing AMR work

A/Prof Benjamin Ong in his opening address stressed that AMR is a challenging translational issue

uring the World Antibiotic Awareness Week 2018, some 300 infectious disease experts convened at LKCMedicine’s Clinical Sciences Building for a two-day conference discussing antimicrobial resistance (AMR) in Asia Pacific and its impact on Singapore. The symposium, jointly organised by LKCMedicine and the National Centre for Infectious Diseases, brought together clinicians, researchers, epidemiologists and policymakers from some 10 Asian countries who presented on the efforts, challenges and barriers to human surveillance, the socioeconomic impacts of AMR and the role of new technologies in the surveillance and diagnosis of this ongoing threat. Their discussions were prefaced by an opening address delivered by Director of Medical Services at the Singapore Ministry of Health Associate Professor Benjamin Ong. During his address, A/Prof Ong, who is also an LKCMedicine Governing Board Member, stressed that AMR is a translational issue and a huge challenge.

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LKCares engages the elderly residents in Singapore neighbourhoods to assess their physical, functional and mental health in partnership with NHG, PA and other organisations such as Singapore Cancer Society

LKCMedicine students screen more than 600 elderly residents in new health screening initiative

KCMedicine students are hitting the road to screen hundreds of elderly residents living in heartland communities in Singapore as part of a new student-led health-screening initiative. Over two projects in March and October 2018, more than 600 elderly residents have benefitted from the LKCares Health Screening, which is a collaboration with the National Healthcare Group (NHG) and People’s Association (PA). “This initiative aims to cement the reputation of LKCMedicine as a dynamic and caring institution, where we emphasise health over healthcare among the general public,” said Low Wei Yang, Class of 2022 student and chair of the LKCares Health Screening committee 2018-19. Joining forces with their partners, the students screened the health of elderly residents in the Pek Kio and Teck Ghee estates in central Singapore, assessing both physical and functional health. Aware that one in five people aged 75 and above shows signs of depression, the students decided to include a mental health assessment that identifies people at risk of or suffering from depression.

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“With the support of the Institute of Mental Health’s Aged Psychiatry Community and Treatment Service, student volunteers underwent dedicated training on how to provide mental health screening in a community setting, and were equipped with the skills required to conduct the depression screening,” said Shi Haixiao, Class of 2021 student and LKCares Health Screening Committee 2017-18 member who was in charge of the inaugural health screening held in the Pek Kio neighbourhood. This decision paid off with several at-risk elderly residents identified and referred for further support. Class of 2022 student Ng Jing Chun, who was in charge of the mental health station at the Teck Ghee screening, said, “Over the two days, we discovered nine at-risk cases and five were referred to the Ang Mo Kio Family Service Centre for counselling.” The students also conducted the functional health screening for those aged 60 and older, while NHG led activities at the physical screening stations, which comprised a blood test and measuring of vital signs. This physical-health screening was open to residents aged 40 and older. At the functional screening stations, students assessed residents’ mobility, risk of falls, and urinary continence. With the support of organisations like the Singapore Cancer Society, they were also able to offer pre-registration for subsidised pap smears and hand out free colorectal cancer screening kits.

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Landmark population health study recruits 1,000th participant

ust six months after its official launch, LKCMedicine’s landmark population health study screened its 1,000 th participant on 2 November 2018. Called Health for Life in Singapore (HELIOS), the study aims to recruit as many as 200,000 citizens and permanent residents to better understand, predict and treat the common chronic diseases that affect Singapore’s ageing population. HELIOS, a partnership between LKCMedicine, the National Healthcare Group (NHG) and Imperial College London, is the most comprehensive population study to focus on ethnic Asians living in Singapore. Similar studies conducted in the US, UK and Germany have focused primarily on populations of European ancestry living in Western countries. To deliver on the promise of precision medicine in Asia, we need to be able to identify those people in the population at high risk of developing diseases such as cardiovascular diseases or diabetes, explained HELIOS lead investigator LKCMedicine Professor of Cardiovascular Epidemiology John Chambers. Some 30 per cent of deaths in Singapore every year is due to heart diseases. “This is simply unacceptable,” Prof Chambers said, adding that the vision is to

Dr Amy Khor, Senior Minister of State for Health and Environment & Water Resources, officially opened the Population & Community Health Laboratories, with LKCMedicine Dean Prof James Best and Governing Board Chairman Mr Lim Chuan Poh looking on

identify the factors that drive disease and to better identify people for preventative measures so they can stay healthier longer. The comprehensive health assessment conducted when participants join the study includes routine items such as questionnaires about lifestyle, diet and exercise as well as molecular tests and scans such as 3D ultrasound imaging to capture data revealing genetic patterns, metabolic and gene expression profiles, and structure and function of organs. Turn to page 36 to get to know more about LKCMedicine Professor of Cardiovascular Epidemiology John Chambers

HELIOS lead investigator and LKCMedicine Professor of Cardiovascular Epidemiology John Chambers briefing Dr Amy Khor on the Singaporean population health study

New labs a healthy shot in the arm

he HELIOS study is among the first studies conducted in the School’s Population & Community Health Laboratories, which were officially opened by Dr Amy Khor, Senior Minister of State for Health and Environment & Water Resources, on 18 June 2018. LKCMedicine Governing Board Chairman Mr Lim Chuan Poh outlined the vision behind these multidisciplinary laboratories housed in the Clinical Sciences Building, saying, “We are officially unveiling LKCMedicine Population and Community Health Laboratories, a suite of new research centres and laboratories on the 18 th floor of this building. Each lab is led by a world-class principal investigator, and the work of the teams within aims to advance efforts in the prevention and treatment of Singapore’s unique disease burden to enable Singaporeans to lead healthier lives.” This burden is expected to rise sharply as the number of people aged 65 years and older will double to 900,000 by 2030. This creates an urgent need, Dr Khor said in her opening address “to move beyond just providing care for those with disease to improving the health of the entire Singapore population. We must focus on wellness, chronic disease prevention as well as education and empowering individuals to take better care of themselves.” The Population Health & Community Laboratories consist of: • The Health Screening Centre, which hosts the HELIOS study • The Exercise Medicine & Physiology Laboratory • The Centre for Primary Health Care Research & Innovation • The Centre for Population Health Sciences • The Centre for Global Health enlighten ed. 1

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The promise of

regenerative medicine Nicole Lim Senior Assistant Director Communications & Outreach

“It has taken much longer to get to this point than we ever imagined, but there have been many hurdles to overcome along the way.” - Professor Phillip Ingham FRS

ust over 25 years ago, then a Senior Scientist at the UK’s Imperial Cancer Research Fund (now known as Cancer Research UK), Professor Philip Ingham FRS was in a race against time to file a patent by New Year’s Eve, when the discovery at stake would be published in the journal Cell. “I spent Boxing Day on the phone to the patent lawyers in Boston while eating my turkey sandwich,” recalled Prof Ingham, who is now Toh Kian Chui Distinguished Professor and Professor of Developmental Biology at LKCMedicine. The intellectual property he and his collaborators from Harvard University were seeking to protect was the discovery of the first known protein with the ability to specify the identities of different neurons, the key cellular components of the human brain and central nervous system. That protein is Sonic Hedgehog. The resulting patent envisaged an application of this discovery in a completely new clinical discipline. Named regenerative medicine, this discipline aims to treat otherwise incurable conditions through the regeneration of diseased cell types and organs. “One of the first conditions we thought about was Parkinson’s Disease,” said Prof Ingham. “Because we knew this to be caused by the degeneration of a specific cell type in the brain, the dopaminergic neurons, and we had good reason to believe that the Sonic Hedgehog protein could instruct naïve progenitor cells to become dopaminergic neurons.” Now, a quarter of a century later, this vision finally seems close to realisation. In July last year, scientists in Japan announced the start of the first clinical trial, in which patients with Parkinson’s Disease will have induced dopaminergic neurons implanted in their brain. And just three months later, a man in his 50s was the first to have 2.4 million of these cells implanted at 12 different sites in his brain to treat this incurable condition. Reflecting on the full timeline, Prof Ingham said, “It has taken much longer to get to this point than we ever imagined, but there have been many hurdles to overcome along the way.”

Two transformative discoveries

Without a supply of progenitor cells from which to generate specialised cells for therapy, the aims of regenerative medicine would have remained a pipe dream. But thanks to two key breakthroughs, the field is now flourishing. The first was the derivation of human embryonic stem (ES) cells by James Thomson and colleagues

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The genesis of regenerative medicine

in 1998. These cells provide the starting material to which proteins like Sonic Hedgehog can be applied to generate specific cells for therapeutic use. These embryo-derived cells presented both technical and ethical challenges, and it took a second breakthrough to overcome them. That breakthrough was the development of induced Pluripotent Stem (iPS) cells by Shinya Yamanaka in 2006, which would earn him the Nobel Prize in Physiology or Medicine in 2012. Both ES and iPS cells have already been used to develop cellbased therapies for the treatment of macular degeneration, the leading cause of blindness among people over the age of 60. But even targeting the relatively simple structure of the retinal pigmented epithelium has not been without its challenges and initial results, although promising, show the field still has a long way to go. In patients suffering from Type 1 diabetes, the immune system attacks and destroys the insulin-producing beta cell; as with Parkinson’s Disease, this highly specific defect makes the condition “a promising target for regenerative therapy as we know exactly what is missing,” said LKCMedicine Assistant Professor Ray Dunn. And transplanting donor islet cells into patients with Type 1 diabetes had been shown to temporarily cure their condition.

Regenerative medicine, a term first coined in 1992, is a relatively new branch at the intersection of medicine, engineering, stem cell technology and developmental biology. LKCMedicine Toh Kian Chui Distinguished Professor and Professor of Developmental Biology Philip Ingham FRS said, “Regenerative medicine encompasses all medical approaches to restoring lasting organ function or regenerating tissue.” Nanyang Assistant Professor Xia Yun, who heads up the Stem Cell Lineage Specification and Organ Regeneration Lab at LKCMedicine, added, “The ultimate purpose is to replace damaged or missing tissue or cell type inside our body, but it is not only functional replacement, it has to be structural regeneration too.” The concept of regenerating failing or diseased organs or body parts has long been a sandbox for the human imagination, giving rise to re-animated beings as imagined by Mary Shelley and HP Lovecraft and self-healing superheroes like Wolverine, but also more insidious creatures like Oscar Wilde’s Dorian Gray who try to escape time. In scientific and medical circles, the first attempts to ‘regenerate’ organs were in the form of transplants. The earliest record of organ transplantation is attributed to Chinese surgeon Tsin Yue-jen (407 – 310 B.C.), who exchanged the heart of a soldier who was strong in spirit but weak in will with the one of a soldier who suffered from the opposite affliction, thus rendering both suitable for battle assuming they had survived the ordeal. It wasn’t until the 19 th century that physicians turned to skin grafts to close skin defects in patients, and not until the 20 th century that organ transplantation became feasible, with the first successful kidney transplant between identical twins carried out in 1954. Twins again underpinned the next milestone, which followed two years later: the first successful bone marrow transplant to treat leukaemia. While tissue and organ transplants brought great hope, the promise of fully restoring function and structures for the long term was often short lived. Patients’ bodies would reject donor organs, or the side effects of the drugs needed to prevent the body from rejecting the foreign organ would weaken the recipient. But perhaps most limiting of all was the availability of donor organs. Nanyang Assistant Professor Christine Cheung, who leads the Molecular & Vascular Medicine Laboratory, said, “Replacement is a zero sum game, we don’t want to go there.” Keenly aware of the state of play, scientists found inspiration in the animal kingdom that there may be something more than just replacement: Cut off a salamander’s entire limb, and it will regrow. “That was the earliest when people started to try to study whether this phenomenon can be translated to mammals, because mammals cannot regenerate an entire organ,” said Asst Prof Xia. While there is a vast gap between reptiles and humans, she added, “To my knowledge this is the earliest very encouraging and fascinating phenomenon driving us to jump into regenerative medicine.”

Con’t on page 16

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Early clinical trials of lab-grown beta cells have already been conducted, but significant hurdles need to be overcome for the long-term viability of this approach. Because the beta cells need to be shielded from the immune system to avoid being destroyed, they have to be encapsulated in a special device. These capsules, however, are prone to scarring as the body mounts an immune response against these foreign entities. In addition, despite their differentiated appearance, the encapsulated cells still retain some foetal characteristics, meaning they are less mature than the cells they are intended to replace. “They are really the endocrine progenitors, the precursors of fully differentiated beta-cells. The hope is that by squirreling them away inside the body they will mature in situ in vivo into cell types that can sense and respond to glucose changes and secrete insulin,” said Asst Prof Dunn, who also holds an appointment as Senior Principal Investigator at A*Star’s Institute of Medical Biology and President of the Stem Cell Society Singapore. Asst Prof Dunn’s own work focuses on understanding how adult-like, or terminally differentiated, human beta cells can be grown from stem cells. While working on this roadmap, he and his team recently made an important breakthrough by determining the conditions under which pancreatic progenitor cells can be maintained and cultured. This significantly reduces the time and costs associated with deriving these cells from stem cells (read more about his work on page 17).

Pluripotent stem cell

Pancreatic progenitor

Endocrine progenitor

Beta cell 80

Reprogramming skill cells

Transplant

Insulin-dependent diabetic

Asst Prof Dunn and his team use stem cells to study diabetes. They direct stem cells to develop through a series of embryonic intermediates into beta cells in the lab. Using these newly grown cells, they can identify problems with diabetic beta cells or replace lost or damaged cells by transplantating healthy ones.

Creating a whole new world with organoids

But cells in the body do not develop in isolation. So in their attempt to grow replicas from stem cells, scientists realised that they had to grow their cells in three

A colony of embryonic pancreatic progenitor cells grown in adherent culture. These cells can be expanded and turned into any of the cell types in the adult pancreas

dimensions. These three-dimensional tissue constructs or organoids create a powerful means to interrogate human biology, a Nature Methods editorial said, crowning them “Method of 2017”. Using this approach to grow entire replacement organs is the long term goal of LKCMedicine Nanyang Assistant Professor Xia Yun. She and her team have already succeeded in coaxing iPS cells to differentiate into the various cell-types that form nephrons, the urine-producing units of a kidney. They have been able to grow organoids that contain all the cellular compartments of a nephron, including the glomerulus and distal tubes. As the kidney’s main function is

Organoids “Here we had the engineers, cell biologists and the clinicians. These are the ingredients to ensure success in regenerative medicine.” - Professor Teoh Swee Hin

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Organoids or mini-versions of many organs, including most recently the placenta and kidney, are being cultured in the lab to interrogate the biology of these organs in health and disease. At LKCMedicine, Nanyang Assistant Professor Xia Yun has focused on growing kidney-like organoids in a dish. Starting with stem cells, Asst Prof Xia and her team coax these cells into nephron progenitor cells and from there into three-dimensional structures which contain all the components of the urine-producing unit of a kidney. Here is how these organoids are grown:

Stem cells are grown into these clusters or colonies, a process which takes about three days

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genes have the biggest clinical impact. Other uses include using organoids grown from a patient’s own stem cells to screen for potential therapies for different diseases such as cancer. In one such instance reported in 2013, researchers developed a personalised organoid-based screening tool for cystic fibrosis patients that allows them to screen the efficacy of different drugs. The organoids are grown from stem cells derived from the gastrointestinal tract. One beneficiary, Asst Prof Xia said, was a 17-year-old boy who carried an unusual mutation in one copy of this gene. After screening a drug licensed for use in cystic fibrosis patients with different mutations in an organoid from the boy’s cells, doctors administered this drug to him. Within four weeks he showed improvements. Since then some 40 others have been treated based on their organoids response to drugs. And just last year, scientists from the University of Cambridge announced that they had successfully developed placental organoids that will transform pregnancy research, advancing knowledge of stillbirths and preeclampsia. For LKCMedicine Nanyang Assistant Professor Christine Cheung, the aim is to understand health to inform how we treat disease. “The grand goal from my perspective is to learn how each organ forms, how it stays healthy, how basic function is sustained and maintained throughout adult life and from it, we

to filter unwanted substances from the blood, vascularisation throughout these compartments is key. And vascularisation of their lab-grown kidney organoids is something that Asst Prof Xia and her team have recently achieved. “The vascular network is generated because we are able to produce glomeruluslike structures in sufficiently large quantities and with sufficient stability,” she said. Like the lab-grown pancreatic beta cells, however, these 1mm to 2mm-wide organoids resemble more the kidneys of a young foetus than of a fully grown adult. To help them mature, these organoids need to be exposed to the naturally present mechanical forces in the body, such as the flow of blood or urine as well as the pressures from surrounding organs. For this, collaboration with engineers will be essential, said Asst Prof Xia.

Bioengineering potential

One area where close collaboration between stem cell scientists, engineers and clinicians has borne fruit is in the regeneration of bones. LKCMedicine Professor of Bioengineering Teoh Swee Hin, who has been working on tissue engineering since the 1990s, has developed flexible biodegradable scaffolds that are soaked in a patient’s own bone marrow, which is full of stem cells. These scaffolds are held together in a web-like titanium frame made to fit the defect. Using such scaffolds, he has coaxed bones to heal in patients around the world. One of the most memorable instances, he said, was a patient who was referred to him several years ago. A car crash had left then-18-year-old Nikita’s world in tatters, killing her parents and shattering her skull. The neurosurgeon who was treating Nikita in Bangalore reached out to Prof Teoh seeking help to repair a hole the size of a grown man’s palm in Nikita’s skull. Prof Teoh and his team set about building a bespoke biodegradable scaffold infused with her bone marrow that would help Nikita’s body to grow new bone to close the hole. It was one of the biggest pieces of bones to be successfully regrown. “Here we had the engineers, cell biologists and the clinicians. These are the ingredients to ensure success in regenerative medicine,” said Prof Teoh. “But the best part was when she sent me a picture of her son.”

On the road to regeneration

While scientists work towards the goal of regenerating tissues and organs that mirror their adult counterparts in structure and function, other benefits are emerging along the way that will inform clinical decision-making in the near term. For example, organoids that represent a particular phenotype can be used for drug screening and toxicity studies, or provide models that can interrogate data obtained from genome-wide association studies in order to understand which

They are then sequentially exposed to differentiation media that are supplemented with specific chemical signals to guide the cells to develop into nephron progenitor cells. Upon reaching the nephron progenitor stage, the subsequent organoid can adopt either a two-dimensional construct (left) or a threedimensional (right) format.

After about one month, the organoid can be seen to have all the components of a urineproducing kidney unit, called a nephron. A nephron consists of glomerulus (green), tubules (blue) and blood vessels (pink)

To study both a healthy kidney and a polycystic one, Asst Prof Xia has developed a way to induce a healthy kidney organoid (left) to develop cysts (right). This polycystic model allows researchers to uncover the mechanisms of this disease for which there is currently no cure.

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DISCOVER know what is perturbed in certain diseases,” she said. Employing this approach, Asst Prof Cheung, who specialises in blood vessel formation and function, has been collaborating with cardiologists and neurologists from NUH to identify key molecular differences between healthy individuals and those who suffer from vascular-related impairments. The aim is to identify new biomarkers that may allow better risk prediction and discover new preventative strategies. “I believe that blood vessel dysfunction arises before many adverse outcomes,” said Asst Prof Cheung, who cited stroke and vascular dementia as key examples. Some 450 to 500 patients enrolled over the past five years have been stratified based on their clinical outcomes. Asst Prof Cheung’s team will assess previously identified biomarkers that indicate blood vessel instability in patients susceptible to vascular complications in this cohort. Having developed methods to grow patients’ own blood vessel cells from their blood progenitor cells or iPS cells, her team will use these personalised vascular models to understand perturbed biological pathways that lead to clinically significant differences among individuals.

Looking ahead to a new universe

Reviewing the developments over the last decade in organoids, Asst Prof Xia believes the field has entered a phase of consolidation. “Over the last five to six years, the protocol to generate, maintain biobank organoids and make them useful for specific purposes, this has been realised,” she said. What is clear is that for now, the main focus remains on

sharpening techniques, developing robust reproducible protocols and delving deep into developmental biology to uncover the fundamental processes that underpin human development. LKCMedicine is home to “a very good mix of basic developmental biologists who generate the knowledge about cellular diversity, understanding the mechanisms which the body itself uses to promote regeneration and looking at organisms which can do it better than we can with the aim of translating this knowledge to see if we can modify the way our own body behaves and take advantage of the body’s intrinsic regenerative capabilities,” said Prof Ingham, who is studying the zebrafish’s ability to regenerate muscle fibre with an eye on potential relevance to humans (see sidebar below for more on his work). To encourage greater crossfertilisation of ideas and get scientists to play in different sandboxes, faculty from LKCMedicine and NTU are joining forces to form a regenerative medicine core. Led by Prof Ingham, the programme is

Fishing for clues to frailty and nerve regeneration

Cross section through the skeletal muscle fibres of a young adult zebrafish: mature fast twitch fibres are stained blue and slow twitch fibres are stained red. Between these two sets of fibres is a population of newly forming slow twitch fibres (green). Work in the Ingham lab focusses on understanding the genetic programme that controls the formation of these fibres, which are capable of replacing degenerating mature fibres

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LKCMedicine Toh Kian Chui Distinguished Professor and Professor of Developmental Biology Philip Ingham FRS has long studied the development of zebrafish, which unlike humans, have the ability to regenerate many organs and tissues. Elucidating the processes that allow fish to regenerate tissues or organs, such as skeletal muscle or the spinal cord may provide clues that can help revive the lost regenerative process in their human equivalents. Prof Ingham and his team have been studying the formation of skeletal muscles in the zebrafish. Just like in humans, the zebrafish’s muscles are made up of two main types of fibres: fast-twitch fibres allow the fish to swim fast over short distances, while slow-twitch fibres help them to keep going over longer distances. But unlike their mammalian relatives, many fish species continue to produce new muscle fibres throughout their life. As part of their studies of muscle development, Prof Ingham’s lab created a mutant line that fails to develop functioning slow-twitch muscle fibres during embryogenesis. Although these mutant fish hatched and grew into normal looking juveniles, they could not swim for long distances as expected. But to the scientists’ surprise, after three months the mutants were swimming as fast and as far as their wild-type counterparts. Analysis of their muscles showed that the adult fish had grown new slow-twitch muscle fibres, a huge feat in regeneration. “Understanding this process could potentially provide a route to reversing the muscle loss that leads to age-related frailty in humans,” said Prof Ingham, while stressing that any relevance and application to humans has yet to be established. In addition to exploring the regeneration of muscle fibres, Prof Ingham is keen to extend his studies to the central nervous system, another organ that the fish is able to regenerate. He envisages collaborating with LKCMedicine Associate Professor Chew Sing Yian who has been developing bio-functional scaffolds to help restore nerve connections after spinal cord injuries. Her team designs aligned nanofibre scaffolds that have the pliability of spinal

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called DETERMIN, to acknowledge the School’s commitment to drive innovation in developmental biology, tissue engineering and regenerative medicine. Going further the clinical experience and perspective will also be key. And with its campus at the heart of HealthCity Novena, LKCMedicine and NTU can play a leading role here. Prof Teoh said, “We felt that we have a very important strategic role in NTU to bring together two very important groups.” While there is currently no silver bullet, everyone working in the field is passionate about and committed to improving patient care. Even a future as envisioned in the popular series Star Trek, where medics can regenerate skin and heal internal injuries with a handheld device, may not be too farfetched eventually, according to Asst Prof Dunn. “I believe in Star Trek,” he said. “Because there are these moments when you get these inflection points where things really rapidly innovate and move.”

cord tissue and loads them with biological cues that will stimulate the spinal cord neurons’ intrinsic regenerative capacity. A key challenge that remains is the long-term sustainability of such bio-functional scaffolds. A/Prof Chew has seen first-hand how a perfectly fitting scaffold loses its shine with time. “We find that there is a huge difference in time points. What looks wonderful at two to four weeks, starts to lose its shine by three months. We need to learn more about the molecular mechanisms that are switched on and off at every step of the healing process, so that we can design bio-functional scaffolds that can support the body’s inherent regenerative capacities,” said A/Prof Chew. This is where new insights from studies in zebrafish could help deepen scientists’ understanding of the regenerative process over time. In addition, A/Prof Chew is currently working with highly personalised scaffolds that have been designed to fit perfectly. Among her next targets are more universal scaffolds that can be customised later to fit a particular injury. She is targeting in particular the scaffolds that can support the kind of spinal cord injury seen in the region, such as injuries sustained from construction and road traffic accidents.

Inspiration from skin biology leads to new shortcut Differentiating stem cells into a desired cell type is time-consuming, labour-intensive and expensive. In the case of the pancreas, it takes around 15 days to coax stem cells into pancreatic progenitor cells. From these cells, all parts of a pancreas will be grown, including the insulin producing beta cells. Scientists know they have reached this intermediate Pancreatic beta-like cells generated in stage of development when the cells suspension culture. The cells have been have two markers – PDX1 and SOX9. stained to show cell nuclei (blue) and cells that LKCMedicine Assistant Professor produce insulin (green). 40X magnification Ray Dunn said, “This is the postal code for the proliferating progenitor cells that will be in the embryo and in the dish.” “So how can we arrest them in that intermediate state and leapfrog over the beginning?” added Asst Prof Dunn, who is also Senior Principal Investigator at A*Star’s Institute of Medical Biology (IMB) and President of the Stem Cell Society Singapore. Such tool building was the task his lab undertook recently. They were inspired by the work of skin and stem cell biologist Professor Yann Barrandon, who in the late 1980s showed that a feeder layer consisting of mouse cells would allow researchers to grow keratinocytes, the most common cell type in the skin’s outermost layer. This method of culturing epithelial autografts has been used to treat patients with severe burns since then. At around the same time when Asst Prof Dunn was looking into this, a former colleague at IMB was investigating whether this same feeder layer would also support the growth of cells from the foetal intestine. “This platform was well established as having this unknown property of allowing you to capture and grow stem cell types and in this case, my former colleague showed it worked quite brilliantly from the cells of the foetal intestine,” he said. As the pancreas and the intestine come from the same embryonic cell type, Asst Prof Dunn decided to give this same feeder layer a go. After a lot of iterations, they were able to grow cells, where every one of them expressed the two key markers – PDX1 and SOX9. Cultured like this, these cells can be frozen, thawed and shipped all over the world. “We are extremely happy about this,” Asst Prof Dunn said, adding that they are now putting the cells to the test to ensure they live up to their promise. And comparative RNA sequencing Pancreatic endocrine cells generated in data are promising. The cells have suspension culture. The cells have been the same capabilities and trademarks stained to show two transcription factors that determine endocrine cell identity: PDX1 (green) as their contemporaries in the and NKX6-1 (red). 5X magnification human embryo. After two weeks of differentiation, about a third express insulin, which is comparable with previous experiments where they started from scratch. While studies are underway to see whether these cells can function well enough to take over insulin production in a rodent model, the team is also working on decoding the precise ingredients in the feeder layer to further simplify the process of growing progenitor cells. Partnering with a Canadian stem cell company, Asst Prof Dunn hopes to one day get rid of the feeder layer. “If we could have our cells in chemically defined conditions it would further simplify their culture,” he said.

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s a kid, falling off your bicycle and scraping your knee, is easily remedied by slapping on a Band-Aid. But what about wounds that don’t heal even with the help of a Band-Aid? What if a gaping, oozing hole remains under your foot for months, with no sign of healing? These non-healing wounds or chronic wounds are a growing global concern, affecting two to six per cent of the population in just the United States itself. Unfortunately, in today’s healthcare climate, this “hidden” epidemic often goes unnoticed, overshadowed by other ailments and remains under-researched with few ways of helping to fully close these wounds.

What are non-healing wounds?

Complementing this work is research conducted at LKCMedicine. The School’s Professor of Tissue Repair & Regeneration David Becker has been hard at work to research on the biology of gap junctions, specifically Connexins, in wound healing and how they contribute to the healing process. Over the years, Prof Becker and his team found that Connexin-43, a gapjunction protein, has to be turned off to accelerate the healing process. “We found that by targeting Connexin-43, we can accelerate the healing process and dampen the

Non-healing wounds are wounds that do not heal, or improve, after four to eight weeks. The most common types of non-healing wounds that exist in Singapore are venous and pressure ulcers, but diabetic ulcers remain one of the biggest concerns in healthcare. The gaping wound that appears mostly under the foot is a symptom of diabetic ulcers, and is especially dangerous as But with efforts underway to re-start the healing many diabetic patients no longer sense process in these wounds, scientists are hopeful that pain in the feet, due to nerve damage caused over time by their elevated blood they could not only save people from amputations, glucose levels. In 2017 alone, an average but that their work would have significant direct of four diabetic patients underwent and indirect economic benefit. amputation every day, with most of amputations caused by diabetic ulcers. This as well as supportive treatment of these wounds with compression inflammatory response to reduce tissue bandages means that a third of the budget dedicated to diabetes in Singapore is swelling,” said Prof Becker. spent on treating ulcers. But with efforts underway to re-start the healing process This discovery led Prof Becker in these wounds, scientists are hopeful that they could not only save people from to create NexagonTM back in 2014 amputations, but that their work would have significant direct and indirect economic with his then-partner, Professor in benefit. Ophthalmology Colin Green from the University of Auckland. NexagonTM is Research saves the day a gel that stimulates and accelerates In recent years, research on the fundamental biological processes underway during wound healing by down-regulating wound healing has stepped up. The Skin Research Institute of Singapore (SRIS), a Connexin-43 protein production. An collaboration between the Agency for Science, Technology and Research (A*STAR), important feature of the NexagonTM National Skin Center (NSC) and Nanyang Technological University, Singapore technology is its capacity to kick-start (NTU), initiated the Wound Care Innovation for the Tropics (WCIT) Progamme. The healing in chronic wounds, something programme is dedicated to research investigating the causes of non-healing wounds that conventional treatment is not able in tropical climates, and the development of novel wound care treatments. to achieve. Deputy Executive Director (Industry), Research Director of Tissue Technologies Prof Becker added, “This gel at the Institute of Medical Biology (IMB), A*STAR Professor Zee Upton, who is has been tested on several patients heading this programme, said, “This new initiative is focused on Asian populations with positive outcomes, and recently and the challenges associated with delivery of care in tropical climates, and the we signed a deal with an American development of fit-for-purpose technology.” Ophthalmology company to run a big As most research has been conducted in temperate climates, like Europe and phase III clinical trial with this. So, it’s the US, only a few studies have been done in tropical countries like Singapore. A few looking very promising.” of the projects that the WCIT team is developing include creating biomarkers for Prof Becker is also part of SRIS and Asian populations for researchers to tap into, and 3D skin models for clinicians to a team leader in WCIT. There, he has test new dressings. The researchers also hope to shed light on how wound healing been working on the second-harmonic is affected when humidity, infection and the differences in pigmentation, genetic imaging microscopy equipment, to break factors and cultural aspects of service delivery come into play. “Some things that you would expect to be different is what types of infections and down the extracellular matrix in human wounds, and find novel biomarkers microorganisms are present in wounds. Compliance is also an issue as putting on a that could identify whether wounds are compression bandage can be uncomfortable in hot weather, making this not a great healing or not. solution,” said Prof Upton.

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Truly non-healing?

Contrary to common belief, non-healing wounds are in fact wounds that could heal if detected and treated early. This is why education and early intervention play an important role in the success of healing these wounds. To help identify these wounds easily, SRIS is setting up a wound registry built from wound samples contributed by all hospitals in Singapore. New imaging technologies are also being developed to help scan non-healing wounds and better identify what prevents these wounds from healing properly. Clinical Professor at Cardiff University School of Medicine Professor Keith Harding, who is part of SRIS, said, “Some wounds can take many months to heal. And it is usually based on biology. We can actually turn non-healing to healing, by changing the biology and also the associated clinical care.”

Dispelling the myth

What unites all the researchers is a desire to dispel the myth of the non-healing wound. With methods to distinguish between pressure ulcers, venous ulcers and diabetic ulcers early on, they believe changes to clinical care can help prevent wounds from exacerbating. With consistent diet and exercise, and early intervention and management of non-healing wounds, these wounds can be prevented. “Many of the so-called ‘non-healing wounds’ are healable, but only if they are seen by clinicians who are aware of the research, educated and trained, and are able to provide a service,” said Prof Harding.

Wounds that won’t heal Sean Firoz Assistant Manager Communications & Outreach

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THINK

top training radiologists. That was the controversial claim made by British cognitive psychologist and computer scientist Geoffrey Hinton in 2016. In 2017, Esteva et al published a paper in Nature, showing that artificial intelligence (AI) can learn to classify skin cancer as accurately as dermatologists, and in 2018, this claim was advanced by a further study by Haenssle et al in Annals of Oncology, that found that AI outperformed experts in the diagnosis of melanomas. Do these advances herald the substitution of human physicians with AI? Or can we harness its computing powers to improve overall patient care through a new hybrid approach? The application of AI in medicine has so far concentrated most heavily on

Are we entering an age of

SUPER-PHYSICIANS? Henk Schmidt LKCMedicine Visiting Professor and Professor of Psychology at Erasmus University, Netherlands

the area of visual diagnoses, because images contain both the explicit and implicit cues needed to arrive at an accurate diagnosis. With deep-learning capabilities, AI programmes can potentially excel, if fed with enough and varied data representing all disease states and permutations.

The potential of AIs in non-visual diagnostics

But what about instances where the information needed to make an accurate diagnosis relies on verbal communication of a patient’s experience of a disease? In a 2010 study by Jones et al published in the British Journal of General Practice, patients diagnosed with coronary artery disease were asked to describe their chest pain. While more than half described a “tight” or “tightening” sensation, a range of other phrases was also used — including “pressure”, “constriction”,

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“sharp”, “stabbing” and more vague terms including “dull”, “stitch-y”, and “tingling”. While these terms, though varied, fit the angina canon (ie, the well-described set of symptoms of cardiac and noncardiac chest pain of patients) and could, therefore, be used as source information for an AI application, other patients used more abstract terminology, including similes, synonyms and slang. Some patients even described symptoms not suggestive of angina, but that they felt were important. Yet in each case, the diagnosis was the same. In Singapore, we have an additional complexity layer: multiple cultural backgrounds and languages that affect how these experiences are lived and described. The reality is that diseases do not always present in a standard way. There is enormous variety both in terms of the stage and presentation of a disease, as well as a patient’s experience of it. Each consult demands that a physician applies his or her clinical reasoning skills anew to deduce the right diagnosis. For that, experiential knowledge is crucial as book knowledge alone is insufficient. A physician becomes an expert through experience built up over years, and decades of seeing many patients and the same diseases in many forms. The experienced physician learns to incorporate knowledge that he or she may not even be aware of. For example, the way a patient smells can be an indicator of certain diseases, and the way they behave or move as they walk into the consultation room, can yield clues about their health. How this tacit knowledge can be incorporated is a challenge that AI has yet to tackle, and some experts in the field, such as the late American philosopher Hubert Dreyfus, argue that such knowledge cannot be effectively captured through formal rules.

A boost to experienced physicians If it cannot supplant the physician, what role is there for AI? AI has the potential to act as an effective support for physicians, particularly in situations where experienced physicians cannot arrive at a diagnosis using their intuition (or System 1 thinking). It has long been accepted in medicine that being able to think fast (ie, using System 1) is the

hallmark of expertise. If an experienced radiologist sees an X-ray and knows very quickly what is going on, he or she is most likely right. But when a diagnosis is not evident to the experienced radiologist, he or she has to engage System 2 thinking – a more considered and step-by-step approach to analysing the information presented. This type of thinking has been shown to result in a greater number of diagnostic errors. In such a case, a support system that has seen thousands of different slides representing the many different representations of disease, may help by offering differential diagnoses for further analysis by the radiologist.

However, it took another 20 years before AI beat a chess grandmaster, and chess is played according to fixed rules and moves.

It could, therefore, be argued that an effective AI support system could boost experienced physicians’ ability to make accurate diagnoses, by suggesting differential diagnoses that the physician may have overlooked. Ultimately, this could result in overall safer patient care.

in turn, describe it. This continues to be the main hurdle facing AI in diagnostic medicine. Even in aviation, the autopilot has not replaced the pilot. Every cadet has to complete a set number of flight hours before he or she is licensed to captain a plane. The same holds true for physicians. Medical students need to understand the relationship of the signs and symptoms with the underlying pathophysiological processes. They need to accumulate experience to develop expertise, and it is then, and only then, that AI diagnostic support devices can make a significant difference. I do believe that there will come a time when such support systems will have developed sufficiently to become useful, but we still have some way to go. In the 1980s, when the first rudimentary AI programmes first emerged, everyone was certain that AI would be better than humans within a few years. However, it took another 20 years before AI beat a chess grandmaster, and chess is played according to fixed rules and moves. Of course, AI has changed gear since then. Now, systems can learn. If you give them enough pictures, they become better and more accurate. But for diagnostic support systems to reach this level of accuracy, we really need another 50 years. © Singapore Medical Association. This article was first published in SMA News in its November 2018 issue.

The wait for the super physician

Such diagnostic support programmes already exist. The user types in the signs and symptoms observed, and the computer produces a number of alternative hypotheses. But they are cumbersome and error-prone, and many residents complain bitterly about such systems’ unwieldiness. Unlike domains which behave according to a set of rules that are clearly defined, like mathematics and aviation for example, medicine operates in grey space with poorly defined parameters that are, in addition, highly subjective and variable depending on who is affected by what disease, how that affects the individual and how they, enlighten ed. 1

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THINK

better or worse?

For for

Charmaine Lee Class of 2018

an you imagine a day when you are being taken care of by robots? Neither can I... Sure, robots are fast, efficient, and rarely make mistakes. Without the assuring words of the physicians, kind touch of the nurses, how would we get

better? April 19, 2070: I make a living making paper crafts, something that allows me to show off my dexterity and fine work which I have honed over many years in my previous job. But, paper is purely decorative, its old uses obsolete now, as with all the skills that I used to practise. I turn a corner into a dark alley looking for a shop to get a gift for my daughter’s wedding, which is in two days. The night air is cold, and I pull out an additional coat which has seen better days. Before I know it, something hits me on the back of the head and warm blood trickles down my neck. A robbery! He drags me to the side and ransacks my pockets as I lie there semi-conscious. Wait. I recognise those hands! The callouses on the little finger, the hands’ swift decisive movements. I look up into familiar, but aged brown eyes. We used to train together, whatever happened to him? Whatever happened to the times we swore to do no harm? As the hypothermia sets in, my mind returns to the past. “Scalpel, please,” said the tall surgeon in his blue cap. We were in a race against time to stop the bleeding vessel. Each beep of the cardiac monitor reminded us of the passing seconds draining the life of our patient. The burly registrar with brown eyes asked, “Should we bring in the new robotics our hospital just bought?” “Surely, no need,” I, then the most junior member of the team, protested. “We’ll be fine.” The robot was used in the end, the rest trusted technology to be better than our own hands and years of experience. Beep... Beep... Beep... Am I still dreaming? The familiar rhythmic chimes of the cardiac monitor slowly get louder. I open my eyes and take in the white walls, light blue curtains, pale gowns. Some things don’t change after all. “Hello Madam, you have been in an induced sleep for two days, three hours and 23 minutes. You have a hairline fracture of the skull, and microbots have been released into your blood stream to reconstruct the bone at the fracture site. There is still some work to be done, I would advise you to lie still.” What did I just hear? “My daughter’s wedding is right now and I need to leave, the fracture will heal. I can’t imagine that I have been put to sleep just for this,” I say to the air. “Madam, you have not yet fully recovered, you will have to continue to be warded.” The voice pauses. “I see that you are angry and upset. I am sorry to see that,” it says in its monotonous voice. They do not know the importance of family, I have to go! I raise my voice hoping someone would come, but as I am getting agitated I feel weaker and drowsier...

This article is one of 52 essays, poems and contributions written by LKCMedicine’s first graduating students, the Class of 2018, and was first published in The Patient Comes First, specially commissioned to commemorate the first LKCMedicine graduation.

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SNAP

LKCMedicine’s

Class of 2018 Graduates

4 July 2018, a date that will forever form part of LKCMedicine, NTU and Singapore’s history. It was the first graduation ceremony presided over by the President of the Republic of Singapore Madam Halimah Yacob as NTU Chancellor. It was NTU President and Distinguished University Professor Subra Suresh’s first ceremony at the helm of the university. And a first for LKCMedicine, a joint medical school by NTU and Imperial, which saw its very first students receive their joint degrees from Madam Halimah. In front of their parents, well-wishers and the many proud faculty and staff from LKCMedicine, NTU and Imperial, the LKCMedicine graduands were presented to Madam Halimah by LKCMedicine Dean Professor James Best and Imperial Faculty of Medicine Dean Professor Jonathan Weber. The ceremony came two months after the then graduands had started work in hospitals across Singapore as junior doctors. Speaking after the ceremony in July, Prof Best said, “They have also been educated to always put the patient first, and I am sure that that will be the legacy of the medical school.”

“We are 52 unique individuals with different backgrounds. However, we have a common identity - being from LKCMedicine, and being the pioneer batch. We were taught from the start to be doctors you and I would like caring for us - and I hope we remember this always.” Dr Leon Tan

Inaugural President of LKCMedicine Alumni Association

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of a

NEW GRADUATE

Let us start with a story.

It’s 1am on a typically busy general medicine night call. I get called to see a patient who has been complaining about an itch. DR JULIA NG

“Uncle, my staff nurse said you’re complaining about an itch?” “Yeah, it’s all over me.”

Dr Julia Ng LKCMedicine Class of 2018 graduate

“How long have you had it?” “Years.” I look at his case notes. He has end-stage renal disease and is due for dialysis tomorrow. No new medications. No active infection. And no obvious rash on his torso or his arms. “Okay uncle, I’ll give you some medicines to help you with the itchiness, okay? The medicine will help you sleep better also.” I walk away, wondering which patient I’d sacrificed to see this benign case of longstanding uremic itch. “Eh eh eh, missy!” There is no missy around because she is on a break. I know who he is calling. I turn around. “Where’s the doctor leh?”

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I’

ve been a house officer for six months. My name tag clearly states DR before my name. I am a doctor, despite my appearance, and I am comfortable in my role today. While I am comfortable working as part of a care team, the people I work with change every month. The closest cousin to this could be speed dating on long-term steroids - which doesn’t even come close. How do you forge relationships quick enough to be strong, strong enough to be effective, and yet transient enough such that when the team changes, it doesn’t feel like a whole part of you needs to be rebuilt again? And that’s where I’m grateful for the emphasis my School has placed on learning soft skills – from communication to teamwork – alongside the science of medicine. Medicine is a deeply social profession, and it is important to know how to be comfortable with different personalities, equal to people of varying hierarchies, be firm yet teachable, and of course, be a charm at speed dates. To this, I think LKCMedicine’s Team-Based Learning system has been spot on. By being assigned to teams at random. By having to work in teams from the get-go. Let’s not forget that the inter-faculty games and other inter-faculty collaborations are crucial elements of this hidden curriculum. It is not just in my interactions with ever-changing colleagues that communication and teamwork skills come in useful. Dealing with patients, their families and their many different expectations can be challenging. When has enough been done for a patient and when was it too little too late? Knowing what the patient’s expectations are starting on treatment, or going into a surgery, are key to help us better communicate what is achievable because medicine is not perfect, and we cannot cure everything. But setting expectations with understanding, empathy and patience, and well-documented case notes (!), will help to smooth rough seas. While I grow into the DR on my name tag a little more each day, I also look ahead and am faced with a new challenge: I am now in charge of setting my own goalposts. Most of my batch mates and I have been primed to think of our future in binary. Residency vs no residency. But that belies the many other opportunities within the wider healthcare system that we can pursue and work towards. Healthcare administration, healthcare informatics, research, teaching, working for a local or international aid agency or even medical writing, are just some of the ways in which we can continue to serve patients and the healthcare system. We need to encourage healthy conversations about our careers early on so that we can prepare early and not feel as though we’ve been ill-informed. Our School’s Scholarly Project in Year 4, our early trips out into the community as part of the long-term patient project are efforts in the right direction.

What they say “The School has prepared them well in terms of communication skills and bedside manner, but importantly that didn’t compromise the acquisition of knowledge and clinical skills.” Associate Professor Chow Wan Cheng Chairman, Division of Medicine Senior Consultant, Department of Gastroenterology & Hepatology Singapore General Hospital

“The School has done really well so far [in preparing graduates for PGY1]… The issue is the need to better align the PGY1 programme, the School and the clinical needs of the hospital.” Assistant Professor Vishal G Shelat

“Hi uncle, the nurse said you have been breathing too fast, are you okay?”

Consultant, Hepato-Pancreato-Biliary Surgery Service PGY1 Programme Director Tan Tock Seng Hospital

“Oh doctor, yes, yes, thank you for coming. The nurse gave me some nebulisers as what you told them to do, I’m okay now.” Wait a minute did you just call me a doctor. I looked down on my blouse and I realise I hadn’t worn my name tag. It’s a dream, right. Yes, this has always been my dream.

Adapted from a speech given at the LKCMedicine Governing Board Advance on 15 November 2018.

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PROFILE

Eyeing diseases through blood vessel formation Nicole Lim Senior Assistant Director Communications & Outreach

hen LKCMedicine Assistant Professor of Molecular Medicine Wang Xiaomeng looked at a spikey 2mm2 patch developed by colleagues at NTU early in 2017, she saw a completely new application for it. The patch had been developed by NTU School of Chemical & Biomedical Engineering Professor Chen Peng and Assistant Professor Xu Chenjie to melt abdominal fat in diabetic mice. But in Asst Prof Wang’s eyes, it had the potential to revolutionise how common eye diseases are treated. “These microneedles can be designed to penetrate different tissue layers, and so we thought perhaps we can use the same technique to deliver drugs into the eyeball,” said Asst Prof Wang, who was working with the Singapore Eye Research Institute (SERI) to explore ways in which to make treatment of chronic eye conditions easier for both patients and clinicians. Currently, many chronic eye diseases are treated with complicated daily regimens of eye drops or frequent and painful injections into the eye which need to be administered by clinicians. The idea to extend the use of this microneedle patch resulted just 18 months later in a breakthrough. Published in Nature Communications in November last year, the three scientists successfully developed microneedles with the right biomaterial properties that could penetrate the cornea without causing pain or damage to the tissue. As the microneedles dissolve, they gradually release a cocktail of drugs, delivering them exactly when and where they are needed for greater efficacy.

Eyeing other opportunities

This is one of a number of projects Asst Prof Wang has embarked on since joining LKCMedicine as one of the School’s pioneer faculty members in 2014. “At LKCMedicine, I feel that I am exposed to many different research opportunities and have more options,” said Asst Prof Wang, who has seized every opportunity to contribute her expertise. And it is this openness that has made her an attractive collaborator. Asst Prof Xu, who works with her on a number of projects, said, “She has an open mind and is willing to take risks to work on a challenging project, qualities that make her an exciting collaborator to work with. Her extensive experience in biology, knowledge of animal models and understanding of medical needs are great assets to my work too.” Asst Profs Xu and Wang are working together on a number of projects from diabetic foot ulcers to establishing a new technology to track gene expression. By tracking gene expression, they hope to develop new diagnostic tools that will give clinicians an early insight into patients’ health before the latter develop symptoms.

Clear vision to pursue her interest

Together with his wife, he would bring Asst Prof Wang and her older brother out of the city to fly kites, hike, and observe the birds and plants. This and the many pets they had at home, sparked a fascination with wildlife in the young girl. During her secondary school days, she got first-hand experience dissecting insects and other animals to inspect their internal structures, a new perspective that fuelled her curiosity and interest. This growing interest first led her to the kitchen. Her father who hails from Southern China where fish is a staple part of the local diet, would often cook fish. Up until her teenage years, his daughter had been an infrequent visitor to the kitchen. Her father, Mr Wang Kunshun, recalled, “This suddenly changed one day. Xiaomeng was very excited when she came back from school. She came into the kitchen looking for a fish. After finding one, she started to clean and gut it. She showed me every single part of the fish and explained each part’s function. From then on, she volunteered to clean all the fish and seafood we cooked until she left home for university.” “I was not surprised that she chose biology as her major at university. With her infectious enthusiasm and curiosity, I knew she would be a good scientist,” added the former journalist, who keeps up-to-date with the work done by his daughter, who is now herself a mother of two.

Asst Prof Wang’s interest in biology was inspired by her father’s passion for nature.

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A hunch with a large payoff

Looking back at her early career in the UK, the project she is most proud of was her postdoc work at University College London (UCL). It was then that her focus shifted from developmental biology, to a more clinically oriented molecular biology approach. Working in the lab of UCL Professors John Greenwood and Stephen Moss, Asst Prof Wang proposed a project that would look into a little known protein that seemed to be implicated in blood vessel formation, or angiogenesis. With just 13 publications about it, Asst Prof Wang had a hunch that this protein called LRG1 could hold the key to angiogenesis. “It was a risky project because we didn’t know its biology or binding partners. Most people had not even heard of LRG1,” she said. Standing her ground in the face of reluctance from her supervisors, Asst Prof Wang started digging around LRG1 and its role in ocular angiogenesis. Her hunch paid off. LRG1 turned out to be one of the most important mediators, contributing to diseases such as age-related macular degeneration. What is especially exciting for her is that the first LRG1 therapeutic antibody is about to go into clinical trials. In 2015, UCL received a multimillion dollar grant to conduct phase I and phase IIa clinical trials, which are scheduled to begin sometime this year. “Seeing this project that started in the lab reach the clinical trial stage has been Juggling career one of the most exciting moments in my career. Hopefully, it won’t be the last. I and motherhood want to find other targets that will lead to “Weekends are all for my better treatments for patients,” she said.

Eyeing ocular diseases from all angles

kids, and during the week, I try to get home by 8pm so that I can play with them before they go to sleep. After they are in bed, I can always do more work.”

Setting up her own lab at LKCMedicine, allowed Asst Prof Wang to diversify the angles from which to study abnormal blood vessel formation. A member of the panel that interviewed her for the position, Prof Ferenczi recalled, “By virtue of the strength of her research output, she was able to secure an Assistant Professorship at NTU. Since joining the School, Xiaomeng has not only built a striving laboratory, bringing together a good and dynamic team of researchers, but she has also established a wide network of contacts across the Singapore research landscape to nurture collaborations, while maintaining her ties to the UK.” Through this network, Asst Prof Wang has become involved in a number of large nationwide projects, including one that aims to identify alternative drug targets for ocular diseases. Known as the SERI – Institute of Molecular & Cell Biology (IMCB) Programme on Retinal Angiogenic Diseases or SIPRAD, the team behind it is screening drug candidates to look for ones that are more effective than current anti-angiogenic drugs. The effectiveness of current anti-angiogenic drugs is limited, as blood vessels stop to respond to them after they have become established. After screening more than 200 drug candidates, the team has found one very promising candidate. “The good thing about this drug is that it does not only target VGEF signalling

pathway. It targets multiple antiangiogenic pathways. In addition, this drug targets both vascular endothelial cells and perivascular cells, so hopefully it will have better efficacy in humans,” said Asst Prof Wang, who was appointed lead co-Principal Investigator in 2018, adding that they are now seeking funds to support further pre-clinical studies.

Extending her sight

In addition to her work with SIPRAD and collaborations at NTU, Asst Prof Wang is involved in two other large collaborative grant projects – one examining the molecular links between diabetic retinopathy and nephropathy, and another that focuses on the unique molecular characteristics of Asian agerelated macular degeneration. But Asst Prof Wang is not contented just focusing on eye-related conditions. Prof Ferenczi said, “Her main discovery, the LRG1 protein, is proving fertile ground for translational research, with potential impact in macular degeneration, cancer and other angiogenic disorders.” It comes as little surprise then that the young biologist, is exploring the role of LRG1 in other organs and tissue types. Working with IMCB Executive Director Professor Hong Wanjin, Asst Prof Wang is deciphering the role of LRG1 in the heart in a project which started in 2014. Instead of inhibiting LRG1 — which most of her other work has focused on — in this project, they are exploring whether injecting LRG1 can help rescue ischaemic tissue in heart failure, by reducing scarring and growing collateral vessels that circumvent blockages. “The beauty about targeting LRG1 is that it inhibits fibrosis and promotes angiogenesis,” said Asst Prof Wang. She added, “My focus is really on these overlapping areas such as the cross-talk between new blood vessel formation and tissue scarring, or angiogenesis and inflammation. Focusing on these intersections allows me to contribute meaningful knowledge and even new therapeutic approaches to many different diseases.” enlighten ed. 1

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PROFILE

Nicole Lim Senior Assistant Director Communications & Outreach

n a white bench in one of the anatomy lab’s alcoves rest several plastinated human hearts, each carefully preserved to reveal the mechanics of the pump that once gave life to its owner. Alongside them rest brand new colourful 3D-printed copies that smell faintly of tangy candy. These 3D-printed models are the brainchild of Assistant Professor Sreenivasulu Reddy Mogali, who has been using the latest technologies to create a hands-on learning experience that is a world away from his own first brush with anatomy, which started with Rib I.

Finding his heart

“That was the first time I touched a real bone,” said Asst Prof Reddy, recalling his first dissection lesson. It was on this September day in 2001 during his Master’s programme that he found his calling: human anatomy. Having narrowly missed out on studying medicine as an undergraduate four years earlier, majoring in anatomy would also get him closer to his dream of working in the medical sciences. But without a background in medicine, some warned that he would struggle to understand the clinical implications of anatomical abnormalities. LKCMedicine Visiting Professor Peter Abrahams, who works closely with Asst Prof Reddy, said, “I have spent my life integrating medicine with anatomy. It is relatively rare to find a younger anatomist who is keen to teach anatomy that way.” “Reddy loves anatomy and imparting knowledge to students. And not just pure factual knowledge, he tries to show them how it will integrate with their clinical skills,” added Prof Abrahams who is also Emeritus Professor of Clinical Anatomy at Warwick Medical School.

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Colouring

Gray’s Anatomy A village to raise a child

Growing up in a remote village with his maternal grandparents, Asst Prof Reddy attended the village’s single-room primary school. Each year, he’d simply move desk. After reaching the last row, his parents moved him between their home and the homes of family and friends. “My parents’ main aim was to provide [my younger brother and me] with a good education as no one in my father’s family studied beyond ‘O’ levels,” said Asst Prof Reddy, whose parents farm onions and groundnuts, the trademark crop of his home state Andhra Pradesh, India. They did everything to get him away from the farm, despite his interest as a child. It took a stint as a field assistant with a pesticide company in April 1997 to persuade him otherwise. Travelling to villages to educate farmers about pest control, Asst Prof Reddy, who had just completed his school leaving exams then, witnessed their plight. “That was the time I decided strongly to go to university to secure a better future,” he said.

Walking Gray’s

Over the course of his career studying and teaching anatomy, Asst Prof Reddy dissected some 30 cadavers, building an encyclopaedic knowledge of the human body and its variations. His favourite structure? The head and neck for their complexity and intricate network of blood vessels and nerves. “Whenever I had a dissection of the head and neck, I used to spare [every] cutaneous blood vein and nerve,” he said. With such attention to detail and what others might describe as a photographic memory, his knowledge rivals the contents of anatomy bible Gray’s Anatomy, an analogy that elicits a resounding yes from his current students. “He is quite an encyclopedia,” said Class of 2021 student Lee Vint Seng. “He is exceptionally passionate about his field of expertise and this endears him to us.”

New ways to a heart

At LKCMedicine, students have been learning gross anatomy studying human bodies and body parts that have been preserved using a plastination technique

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But 3D-printed models may still fill a niche in surgical training. At the Association for Medical Education in Europe Conference 2018 held in Basel, Switzerland, Asst Prof Reddy presented the results of an evaluation of 3D-printed multi-material airway training models for bronchoscopy simulation. “The airway models show great promise as task trainers for bronchoscopy at a much cheaper cost [and] with increased realism,” said Tan Tock Seng Hospital Senior Consultant Radiologist Associate Professor Gerald Tan, adding, “I envisage that the day may come when these models will be able to fulfil a large part of both our undergraduate and postgraduate teaching needs.”

The magic of anatomy

pioneered by the creator of the Body Worlds exhibition. With growing student numbers, Asst Prof Reddy, who heads the anatomy team at the School, began looking into additional resources to supplement the plastinated specimens that would be equally accurate. The day NTU opened the Singapore 3D Printing Centre in 2015, he emailed its director with an idea. Twenty minutes later, he had a partner. “It was a timely request as I had also started to look into printed anatomy models, but not at the [level of] detail that Prof Reddy initiated,” said Assistant Professor Yeong Wai Yee, Programme Director (Aerospace & Defence) at the Centre. The 3D-printed heart models were the first to be used in teaching in October 2018, and Asst Profs Reddy and Yeong are now working on blueprints for the rest of the body. They hope to have the full upper and lower limb models printed by April 2019. For medical schools that cannot afford the multimillion-dollar budget of an anatomy lab, further enhanced versions of these 3D-printed models could even be a substitute. “But not for surgeons,” cautioned Prof Abrahams. “They need to know what the tissue feels like.”

Adding to the 3D-printed specimens, Asst Prof Reddy is turning to augmented reality (AR) to create digital 3D copies of the original plastinated organs and body parts, so that students will be able to study anatomy via a mobile app outside of the lab. This latest project comes in the form of a MagicBook, which is a collaboration with LKCMedicine Associate Professor of Human & Microbial Genetics Eric Yap. “We want to give students digital 3D models of our own plastinated specimens so that they can relate them to the specimens in class,” said Asst Prof Reddy of the MagicBook, which will come complete with annotations proposed by students and vetted by him. Eventually, students will be able to study the School’s entire collection of specimens, something they may not have time to do otherwise. Asst Prof Reddy hopes that the MagicBook will come in useful beyond the pre-clinical years when the students are working in hospitals. He is also working on translating this AR project into a platform that can be interacted with using VR technology. In a world where anatomy is increasingly compressed for undergraduates, Asst Prof Reddy is creating new ways to make anatomy learning accessible anywhere, any time. Because as Asst Prof Reddy says, tomorrow’s medicine is only as good as today’s anatomy, and he is making sure that his students get nothing but the best.

“We want to give students digital 3D models of our own plastinated specimens so that they can relate them to the specimens in class.”

The left is 3D-printed model of the knee and the right is the plastinated specimen of the same

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PROFILE

Meet LKCMedicine’s two new Chair Professors

A busy year ahead for first Chair Professor in Neuroscience Amanda Lee Senior Assistant Manager Communications & Outreach

rom working on a Strategy Working Group (SWG) in the field of neuroscience to dementia research, Professor George Augustine wasted no time getting into action after assuming the role of first Chair Professor in Neuroscience at Lee Kong Chian School of Medicine (LKCMedicine). “This honour allows me to project neuroscience and the profile of neuroscience more within LKCMedicine, and also within NTU, more generally,” said Prof Augustine, who is also LKCMedicine’s Professor of Neuroscience & Mental Health. A foremost name in the field of neuroscience boasting a rich research experience, Prof Augustine is well-known for his studies on brain synaptic mechanisms but diving into dementia research has been at the top of his priority list for years. Last August, he won a Ministry of Education (MOE) Tier 3 Type B fiveyear grant of $19 million for a dementia research that is part of the Ministry of Health’s push to address the needs of Singapore’s fast ageing population. Late last year, adding to his accolades, he was the inaugural Irene Tan Liang Kheng Chair Professor in Neuroscience. The dementia research is timely as the number of people suffering from dementia in Singapore has increased in recent years. Studies show that about one in 10 people here aged 60 and above suffers from dementia. With the clock ticking, dementia research has been nothing short of exciting. Prof Augustine shared that the MOE grant will be used to obtain and maintain genetically engineered mice for his lab. He added that the endowment fund will be used to fill in some gaps that the MOE grant is unable to support. The first few experiments in his dementia research involve examining brain molecular changes associated with dementia. “We are just getting at the point where we literally got the first initial results as of last month,” said Prof Augustine. “It looks promising but it’s too early to say anything.” As the first LKCMedicine Chair Professor in Neuroscience, Prof Augustine has also been busy growing the neuroscience community. He led and organised faculty meetings and monthly seminar series among neuroscientists within LKCMedicine. He is also co-leading a SWG – convened by NTU President Professor Subra Suresh – in neuroscience, cognitive science and the science of learning alongside National Institute of Education’s Director Christina Goh. “The SWG will help to establish various things related to Neuroscience, including connections between Neuroscience and the Science of Learning,” said Prof Augustine. “However, the initial focus will be on NTU, rather than Singapore as a whole. We eventually hope to connect together all of the neuroscientists in Singapore.”

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Besides the neuroscience community, Prof Augustine is also looking at tapping on the endowment fund to support three to four PhD students in their research projects. His team is in the midst of procuring equipment with novel technologies to help these students in their research projects. Noting that Singapore will see more patients suffering from dementia in the next 30 years, Prof Augustine said, “The pot of gold at the end of the rainbow is that if we can figure out what goes wrong with the basic mechanism of the brain and circuits that are involved with information processing, we may really be able to revolutionise the way people think about dementia and ultimately try to prevent dementia.”

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New dimensions to fight diabetes Andy Kwan Writer Communications & Outreach

“Y

ou should stop using your smartphones when you are eating,” says Professor Bernhard Boehm from the Lee Kong Chian School of Medicine (LKCMedicine). In his opinion, doing anything else during mealtimes, such as using mobile devices to play games or read emails, and in the process rushing your food down your throat, will increase the stress hormones in your body. “The causes of diabetes are mostly environmental, and could be prevented if only we are conscious about it. It has been proven by research that lifestyle habits could induce the increase of stress hormones and lead to diabetes,” he explains. The exhortation is not without basis. After all, as an endocrinologist, Prof Boehm is highly respected for his research in diseases related to hormones, especially diabetes. He is also Professor in Metabolic Medicine and a Principal Investigator in Immuno-Metabolism Laboratory at LKCMedicine. “The human body has a very sensitive recognition system. If there are too many interruptions around you, your stress hormones will go up. In the long run, this will increase your body weight and cause harm to your heart, muscles and even your sleep. You will become less insulin sensitive and this forms the basis for the development of diabetes, in addition to an unhealthy diet,” he cautions. Prof Boehm will have more ammunition to prove his findings to naysayers. In January 2019, he was appointed to the Ong Tiong Tat Chair Professorship in Diabetes Research, made possible by a generous donation from the Estate of the late Madam Irene Tan Liang Kheng to LKCMedicine (please refer to page 8 on this article). Prof Boehm, who hails from Germany, joined LKCMedicine in 2013 as one of the founding professors. A medical graduate from the Johann Wolfgang GoetheUniversity in Frankfurt am Main, Germany, he was first drawn to find out more about diabetes when he saw how his mentor, Professor Karl Schoeffling, researched and innovated a medication to treat diabetes which is still used around the world today. The treatment for diabetes has significantly changed and improved over the years. But if Prof Boehm has his way, he believes education is an important tool in the day-to-day self-management of diabetes. “Implementing self-management at diagnosis has proven to be cost-effective with reduced hospital admissions and a lower risk of complications,” he says. “With proper counselling and training, a diabetic patient could be on the route to recovery. While the advancement of diabetic medicine may help to slow down or even eradicate the loss of vision or leg amputation in serious cases, these worst scenarios could be prevented if a patient is better engaged and informed, and can therefore follow the doctor’s orders to properly self-manage the disease,” adds Prof Boehm who has received research training from medical institutions in Germany, Denmark and the United States. With his newly appointed professorship, he hopes to devote more time researching deeper into the development of Type 2 diabetes amongst different ethnic groups in Asia. “There is a dramatic rise in Type 2 diabetes in the 18- to 40-year-old age group, and particularly in Singapore. It’s not just an elderly disease only anymore,” he discloses. His team would look deeper into the co-relations between age, ethnicity and lifestyle in diabetic patients from the region. From the findings, he hopes to develop treatment methods that would correspond with these co-factors.

“The ways we treat diabetic patients have changed significantly. We don’t just bring down the glucose in blood. We also need to tackle blood lipids, cholesterol and blood pressure. All said, we still have to be very cautious with these co-factors. Diabetes has developed new complications and it’s not a glucosecentric disease anymore but a multifaceted one,” says Prof Boehm. Prior to joining LKCMedicine, Prof Boehm was the acting Dean (Graduate Medical Studies) of Ulm University in Germany. He has also worked in the Department of Internal Medicine at the Johann Wolfgang Goethe-University Medical Centre, Germany. Amongst his achievements in the area of diabetes is the pioneering research on autoimmune diabetes in children and classical and atypical autoimmune diabetes forms in adults. He is also one of the first to set up population-based cohorts to study diabetes development in children and adults and has developed indepth research on risk factors related to micro- and cardiovascular complications. For his research excellence, Professor Boehm has won prestigious awards including the Gerhard Hess Award from the German Research Council and the Ernst-Friedrich Pfeiffer Award from the German Diabetes Association. To date, Prof Boehm has published more than 400 papers in international peer-reviewed journals, and more than 25,000 citations as of 2018 in the field of diabetes, endocrinology and metabolism. He is also the editor for several textbooks in diabetes mellitus and clinical chemistry, and has also coedited several international journals.

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PROFILE

Meet LKCMedicine’s STaR Investigator Award winner

Battling chronic diseases with research

Amanda Lee Senior Assistant Manager Communications & Outreach

all began with his first lecture as an undergraduate at Oxford University. In that lecture, world-renowned epidemiologist Sir Richard Doll showed the impact of epidemiology on populations and future generations. That topic sparked Professor John Chambers’ interest in addressing population-wide health problems. “What’s distinctive about epidemiology is that our focus is upon a problem, and we’re perfectly happy to use any tool in the book to address it,” he added. A cardiologist by training, today he is LKCMedicine Professor of Cardiovascular Epidemiology and Director of LKCMedicine’s Health Screening Centre. The LOLIPOP study was rewarded millions of pounds in grants, which paid for extensive state-of-the-art molecular phenotyping and a string of publications in journals such as Nature and Nature Genetics. Concurrently, Prof Chambers holds the role of Director of the NIHR Global Health Research Unit for Diabetes and Cardiovascular Disease at Imperial College London, and is an experienced physician in research. In 2002, he embarked on a major UK research study – investigating the mechanisms underlying heart disease, stroke, diabetes, obesity and other major medical problems – with his mentor, Imperial Professor of Clinical Cardiology Jaspal Kooner. Called the London Life Sciences Prospective (LOLIPOP) study, it is a firstof-its-kind cohort study of South Asians living in London. The idea for the study

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came from the clinical need both of them faced while working at a district general hospital in north-west London. Prof Chambers, who was then a trainee cardiologist, found that majority of his patients were South Asians and significantly younger than their European counterparts. “I would treat patients who were as young as in their 20s, for heart attacks and diabetes,” he added. “This is an extraordinary clinical problem for these individuals, but also on a population scale.” While the study presented a problem of South Asians living in London, Prof Chambers is curious if environment plays a role in individuals being at risk of diseases. To feed his curiosity, Prof Chambers conducted a similar study, but this time in South Asia. He spent the next five years travelling the Indian subcontinent to recruit and equip local clinicians and researchers with the skills to conduct a similar population-based study. “Like LOLIPOP, this study will take 10 years to yield results,” said Prof Chambers, who is now leading LCKMedicine’s landmark population health study – the Health for Life in Singapore (HELIOS) study. HELIOS – a collaboration between LKCMedicine, the National Healthcare Group (NHG) and Imperial College London – is the most comprehensive population study to focus on ethnic Asians living in Singapore. The study aims to recruit as many as 200,000 citizens and permanent residents to identify genetic and environmental factors that underpin the development of obesity, diabetes, cardiovascular and other complex diseases in Singapore. As of 2 November 2018, the study has screened its 1000 th participant. “Coming to Singapore and LKCMedicine was a natural next step, locating me at the heart of the populations I hope to study,” said Prof John Chambers. “My work with HELIOS will help LKCMedicine deliver a unique cohort study for Singapore, while for me, it will strongly contribute to my ambition, before I die, to describe why these populations have higher risks of cardiovascular and metabolic diseases.” To further fuel his research ambitions, in April 2017, Prof Chambers received the National Medical Research Council’s most prestigious award – the Singapore Translational Research (STaR) Investigator Award. With the award, he is able to support another project of his, a five-year study “Translating ‘Omics’ into a Stratified Approach for Prevention of Type 2 Diabetes”. The study looks at whether disturbances in DNA methylation – a regulator that switches genes on and off – and other molecular biomarkers can be used to help identify and treat people who are at high risk of developing Type 2 diabetes. Diabetes is a major public health problem that affects 450 million people globally. South-east Asians make up about 20 per cent of the people with diabetes, with many of them living in Singapore, Malaysia, Thailand and Indonesia. Prof Chambers is working with physicians from Tan Tock Seng Hospital who will screen obese subjects, identify those with unhealthy metabolic molecular profiles and randomise them into intervention or no intervention. For now, well and truly rooted in Singapore and Asia, he said, “If we take a group of obese people, perhaps only one in 40 develops diabetes per year. But how can we pinpoint and treat the right person? That’s what I want to find out.”

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TOAST

2018 Achievements at a glance LKCMedicine reached a milestone in 2018 with its inaugural cohort entering the workforce as junior doctors. The postgraduates are working in various hospitals across Singapore, where they will continue their training as medical doctors in various broad-based specialties such as general surgery, internal medicine and obstetrics, before applying for residency programmes in specific specialisations. Here is a snapshot of the medical school’s achievements and highlights throughout the year.

Awards 6 February NTU Safety Innovation Award 28 March iGave Platinum Award 26 May Ms Caroline Pang received a Professional Service Award 2017 from the

Library Association of Singapore

2 June APEX 2018 Awards of Excellence for:

- Writing – Feature Writing for the article “Where Will the Future of Healthcare Take Us?”

- Campaigns, Programs & Plans – Events & Meetings for the event “Official Opening of the Lee Kong Chian School of Medicine”

10 July Ms Ramani Saravanan was awarded the WorldSkills Singapore (WSS) Long Service Award

27 July Asst Prof Hiroshi Makino was awarded the Japan Neuroscience Society

Young Investigator Award

9 August Prof Pang Weng Sun and Mr Chan Wei Chuen both received the National Day Award

12 August Nanyang Asst Prof Christine Cheung was named Honouree of JCI Ten Outstanding Young Persons of the World award

11 September LKCMedicine faculty honoured with five Nanyang Awards

- Prof Lionel Lee for Service

- Assoc Prof Tham Kum Ying for Nanyang Education Award (College)

- Assoc Prof Nigel Tan for Nanyang Education Award (School)

- Asst Prof Yusuf Ali for Nanyang Education Award (School)

- Nanyang Asst Prof Luo Dahai for Nanyang Research Award (Young Investigator)

Major grants • Prof George Augustine won MOE Tier 3 grant of $19 million to lead dementia research • MOE AcRF (Academic Research Fund) Tier 2 Winners: Asst Prof Yasunori Saheki, Asst Prof Navin Verma, Nanyang Asst Prof Hiroshi Makino, Nanyang Asst Prof Christine Cheung, Prof Bernhard Boehm • NMRC (National Medical Research Council) OF-IRG (Open Fund – Individual Research Fund): Nanyang Asst Prof Luo Dahai, Nanyang Asst Prof Xia Yun • NMRC HSRG (Health Services Research Grant): Nanyang Asst Prof Luo Dahai, Nanyang Asst Prof Xia Yun • NMRC HSRG (Health Services Research Grant): Prof Helen Smith (2 awards) • NRF-ISF (National Research Foundation; Israel Science Foundation) Joint Research Grant: Assoc Prof Suresh Jesuthasan

LKCMedicine faculty honoured with five Nanyang Awards

7 November Nanyang Asst Prof Christine Cheung received L’Oréal Singapore For Women in Science National Fellowship Award

7 December Ms Ang Wei Wei won the NTU Admin Excellence Merit Award

• A*STAR (Agency for Science, Technology and Research) IAF-PP (Industry Alignment Fund –Prepositioning Programme): Prof John Chambers, Prof David Becker, Asst Prof Navin Verma, Assoc Prof Josip Car, Nanyang Asst Prof Christine Cheung enlighten ed. 1

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Student achievements 3 February Year 5 students Celine Tan won 1st place while Damon Tan won 2nd place for their oral presentations at the 6th International Congress of Infection Control Association (Singapore) 11 May Five LKCMedicine student

teams won inaugural Professor Jenny Higham Collaboration Award

Prof Pang Weng Sun appointed Deputy Group Chief Executive Officer (Population Health) in National Healthcare Group

Notable appointments 15 January Assoc Prof Chin Jing Jih appointed Deputy Chairman (Medical Board) at Tan Tock Seng Hospital

15 January Prof Pang Weng Sun

appointed Deputy Group Chief Executive Officer (Population Health) in National Healthcare Group

8 August Assoc Prof Koh Nien Yue

appointed LKCMedicine Assistant Dean for Year 3

13 August Prof George Augustine appointed the Irene Tan Liang Kheng Chair Professor in Neuroscience 22 August Nanyang Asst Prof Luo Dahai appointed the LKCMedicine lead and representative for the Global Virus Network 28 August Prof Balázs Gulyás was elected as a member of the NTU Senate Steering Committee 1 September Prof Lionel Lee was appointed LKCMedicine Executive Vice-Dean, Strategic Relations & International Affairs

1 September Mr Chan Wei Chuen

appointed LKCMedicine Chief Operating Officer

1 November Prof Philip Ingham

- Year 4 student Sieow Je Shen and Imperial student Amruni Choudhari on OCIP Davao - Year 4 students Jonathan Koo, Ng Wei Xiang and Beverley Lim and Imperial student Dania Badran on comparing patients’ perspectives on primary care in Singapore and the UK - Year 4 student George Lin and Imperial student Julia Graef on Project Songkeum - Year 4 students Aletheia Chia and Goh Kang Shiong, LKCMedicine alumnus Lavisha S Punjabi, Imperial students Jake Mossom, Simon Rabinowicz and Uddhav Vaghela on ProjectPal

was selected as President of Claustrum Research Society

19 March Launch of The Academic Respiratory Initiative for Pulmonary Health (TARIPH) 16 May Opening of LKCMedicine Heritage Centre

18 June Opening of LKCMedicine

Population and Community Health Laboratories

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Wei won the Lee Kuan Yew Gold Medal and the Koh Boon Hwee Scholars Award

24 July LKCMedicine alumnus Moses Ko won the Koh Boon Hwee Scholars Award

18 August Year 3 student Tan An Sen won the Best Oral Paper in the Farrer Park Hospital 3rd Annual Scientific Meeting 22 Sep Year 3 student Tan An Sen won Best Poster (Clinical Research – Junior Category) at the SingHealth Duke-NUS Scientific Congress 5 Oct Year 3 student Tan An Sen won 1st Runner Up, Platform Presentation at the 5th Pathology ACP Research Day

7 August Year 5 student Isabelle Yoong

- LKCMedicine alumnus Eugene Leong and Imperial student Gargi Smarth on collaboration between LKCMedicine and ICSM Surgical Societies

Conferences and Symposiums

24 July LKCMedicine alumnus Julia

Ng won the Academy of Medicine (AMS) Singapore Medal

24 July LKCMedicine alumnus Lavisha S Punjabi won the College of Family Physicians Prize

24 July LKCMedicine alumnus Leon

Tan won the Anthony SC Teo – Gordon Johnson Gold Medal

MOUs and MOAs 20 February Establishment of

won Feng Pao Hsii Rheumatology Prize

22 & 23 January Centre for

Population Health Sciences (CePHaS) Digital Health Workshop

1 & 2 February International Young Investigators Symposium 6 & 7 March Frontiers in Mental

Health Symposium 2018 – Advancing Research in Depression and Psychosis

19 March 2nd International Symposium on Respiratory Research 21 & 22 March Microbiome in Host Physiology & Ageing Workshop – Opportunities & Challenges 22 May Stem Cell Symposium – Regenerative Medicine at a Glance

19 June Joint establishment of teaching programme between LKCMedicine and Farrer Park Company

14 – 16 August Digital Campus and Learning Transformation: Immersive AR/VR, Blended Learning Innovations, Analytics and Next Generation Learning Spaces Conference

25 October LKCMedicine signed an MOU with NHG on a Joint Programme for Clinician-Scientist Development

Health Singapore Scientific Meeting and Symposium

Singapore Brain Bank between LKCMedicine, NHG & NNI

New Centres

24 July LKCMedicine alumnus Ang Jia

- LKCMedicine alumni Joey Wong, Claudia Tong, Lee Hai Quan and Imperial student Jack Teh on comparisons in TBL, PBL and traditional lectures

appointed the Toh Kian Chui Distinguished Professor

3 November Prof George Augustine

LKCMedicine students emerged top at the 6th International Congress of Infection Control Association (Singapore)

25 October ALIVE team/project with students from NYP, NP, RP, SP, TP to work on internships to co-develop serious games prototypes

29 September Society of Behavioural 9 & 10 November Transform MedEd 2018

13 & 14 November Antimicrobial Resistance in the Asia Pacific and its impact on Singapore

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TOAST

Collaboration Agreements Material Transfer Agreement

12 January NTU-SGH (Nanyang Asst

Prof Guan XueLi)

15 January Massachusetts Institute of Tech (Assoc Prof Suresh Jesuthasan)

17 January NTU-National Institutes of Health (Prof George Augustine)

1 July NTU-LNWUH NHS Trust (Prof John Campbell Chambers)

12 July NTU-TTSH (Nanyang Assistant Professor Guan XueLi)

20 July KIT (EZRC)NTU (Assoc Prof Suresh Jesuthasan)

February Gangagen-NTU (Nanyang

Asst Prof Luo Dahai)

23 July University of Chicago-NTU (Prof David Becker)

23 February TTSH-NTU (Nanyang

1 August Samsung Medical Centre-

Asst Prof Guan XueLi)

26 February MRC-NTU (Nanyang Asst Prof Hiroshi Makino)

26 February Salk Institute-NTU

NTU (Assoc Prof Kevin Pethe)

9 August Coriell-LKCMedicine (Assoc Prof Joanne Ngeow)

23 August NTU – Northwestern Uni

20 April Project Agreement SBIC-

NTU-SysteMED (Prof George Chandy)

20 April Project Agreement NTU-IMB (Assoc Prof Josip Car)

30 April 1st Amendment to Project

(Prof George Augustine)

Agreement NTU-SLH (Assoc Prof Josip Car)

George Augustine)

Non-Disclosure Agreement

12 March NTU-ICGEB (Nanyang

26 June Project Agreement NTU-KKH (Assoc Prof Josip Car)

15 January NTU-SIEMENS (Prof

28 June Variation 1 to Project

(Nanyang Asst Prof Hiroshi Makino)

26 February Janelia-NTU (Prof Assistant Prof Luo Dahai)

15 March NCCS-NTU (Assoc Prof Joanne Ngeow Yuen Yie)

21 March MRC-NTU (Nanyang Asst

Prof Hiroshi Makino)

2 April NUS-NTU (Prof John Campbell

Balázs Gulyás)

22 February NTU-Bio Basic Asia

2 July 1st Amendment to Project

9 March BCT-NTU (Prof John

13 July Project Agreement SERI-NTU

Pacific (Prof George Chandy)

(Asst Prof Wang Xiaomeng)

20 March ARYA NOBLE-NTU (Asst

13 July Project Agreement NUS-NTUBTI (Prof Walter Wahli)

28 March SHCPL-NTU (Prof Balázs

26 July 1st Amendment to Project Agreement NTU-TTSH-IMB (Assoc Prof Josip Car)

Prof Navin Kumar Verma)

4 April MIT-NTU (Prof George Augustine)

Gulyás)

4 April University of North Carolina (Prof George Augustine)

14 May NTU-Medisafe (Assoc Prof

5 April MSU-NTU (Assoc Prof Kevin

1 June NTU-ESCO Ventures X Pte Ltd

Josip Car)

(Prof George Chandy)

9 April ATCC-NIAID-NIH-HHS-NTU

(Assoc Prof Eric Yap Peng Huat)

9 April NTU-MBL (Prof George

Augustine)

Project Agreements

15 February Project Agreement NTUSERI (Asst Prof Navin Kumar Verma)

9 April Yale Uni-NTU (Nanyang Asst Prof Yasunori Saheki)

12 March Project Agreement NTU-

18 May TTSH-NTU (Visiting Prof

28 March 1st Amendment to Project

Birgitta Henriques-Normark)

11 June Astrazeneca-NTU (Asst Prof Sanjay Haresh Chotirmall)

13 June NUS-NTU (Prof John

Agreement TTSH-NTU

Campbell Chambers)

Chambers)

Pethe)

Agreement NTU-NUS

NHGP (Assoc Prof Josip Car)

Agreement NTU-NUS

3 April 1st Amendment to Project

Agreement NTU-IMB (Assoc Prof Josip Car)

Campbell Chambers)

Corporate social responsibility 24 & 25 January LKCMedicine SGMarrow Donation Drive

21 February Lunar New Year Community Outreach at Ren Ci Hospital 24 & 25 March Pek Kio Health Screening 2018

7 April Family Fair for Autism 2018

31 July Project Agreement FerringNTU (Prof Walter Wahli) 13 August 1st Amendment to Project Agreement TTSH-NTU-SigN (Asst Prof Hou Han Wei) 17 August 1st Amendment to Project Agreement TTSH-NTU (Prof David Becker)

1 October Project Agreement NTU-

TTSH (Nanyang Asst Prof Guan XueLi)

8 November 1st Amendment to

Project Agreement SingHealth-SGHNTU (Asst Prof Yusuf Ali)

8 November Project Agreement NTUNNI (Prof Balázs Gulyás)

16 May Dover Park Hospice Volunteer Training for LKCMedicine Students

6 October Second student-organised health screening for Teck Ghee residents

18 December LKCMedicine

Christmas Markets proceeds donation to Dover Park Hospice enlighten ed. 1

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PARTNER

Meeting IR 4.0 h In

an episode called “Nosedive” from the Netflix original series Black Mirror, society uses an eye-embedded app that indicates every single person’s social rating based on their daily activities and social media clout. This social rating depicts the type of job or privileges you are entitled to in the world out there. Fiction, you say? Not for China. Rapidly advancing China has made a move with the introduction of their social credit system, a system where trustworthy individuals will be rewarded and those who commit social misdeeds like fraud and spreading slander will be discredited and thus, stripped from certain privileges like purchasing air tickets for travel. NTU President and Distinguished University Professor Subra Suresh said back in February 2018 that the Fourth Industrial Revolution or Industry 4.0 is here, a revolution in technology where artificial intelligence (AI), virtual (VR) and augmented reality (AR) are assimilated into everyday life and improve society as a whole. Addressing NTU faculty, staff and students at his inauguration, Prof Suresh said, “NTU faculty, staff and students have emerged among top research leaders in Asia and the world in many key areas that are now shaping the early stages of Industry 4.0 on a global scale.”

quality security at a lower cost. This is crucial in present-day Singapore, where everyone is connected 24/7, making us vulnerable to cyberterrorism. Executive Director of the Cyber Security Research Centre @ NTU Professor Thambipillai Srikanthan said, “The key advantage of machine learning algorithms is that they can adapt as time progresses. Hence, they can easily respond to variations in attacks.” An example of this use of AI is the classification capabilities, which can help security experts categorise incoming threats and analyse them quickly and efficiently from unwanted breaches.

Artificial Intelligence is here to stay

Where does VR and AR stand?

While AI gets a bad rap from mass media and Hollywood, NTU recognises how AI could actually help us in ways that the human eye cannot see, like healthcare and security. To tackle this relatively new area, NTU recently collaborated with American multinational semiconductor company AMD to launch the Data Science and Artificial Intelligence Lab, which will grow next-generation tech leaders with industry-driven digital skills. This $4 million joint Data Science and AI Lab is a great opportunity for developers to hone their skills by using AMD’s deep-learning technologies and NTU’s strengths in machine learning, AI and data science to work on big data and analytics. NTU’s Dean for the College of Engineering Professor Louis Phee said, “This collaboration with AMD highlights NTU’s drive in nurturing strong relations with top industry partners to provide students with industry-relevant education. This will not only give them first-hand insights in solving real-world challenges, but also give them an edge when navigating today’s dynamic workplace environment.” But AI is a field that is no stranger to NTU. The Data Science & Artificial Intelligence Research Centre (DSAIR) was created in April 2017 to build capabilities in data analytics and AI. The centre is big on combining NTU’s deep expertise in AI and machine learning with data analytics to create new technologies both locally and abroad. This enables the centre to delve into how AI can help mine data for different industries, such as the healthcare sector, where AI is used to extract information hidden in large clinical data sets to create a clear understanding of the relationship between the determinants of disease onset and the severity of it. Director of DSAIR and Chair of the School of Computer Science and Engineering Professor Ong Yew Soon said, “Machine learning in connection with data science can help people analyse data in smarter ways, incorporate feedback and develop models trained on available datasets.” Besides DSAIR, other communities in NTU are venturing into AI, such as the Cyber Security Research Centre @ NTU and its use of AI to secure data. The research centre uses AI to learn algorithms and detect cybersecurity threats to networks, which could surpass human abilities to spot intrusion and provide high-

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While AI is coming in fast, technologies such as VR and AR have already been implemented in our everyday lives. VR goggles and AR apps are available all over the internet, and developers are constantly creating new ways to use this technology as a tool for entertainment and learning. At the Centre of Excellence for Testing & Research of AVs-NTU (CETRAN), VR is used to test out scenarios of autonomous vehicles in a city, instead of real-life tests which are risky. CETRAN developed a virtual autonomous car and a virtual city of Singapore, where the centre could understand the way humans and autonomous vehicles would interact in the real world. “We have effectively created two separate virtual systems, using one to understand how the other will respond,” said Programme Director of CETRAN Mr Neils de Boer. “This allows us to test the vehicle and expose it to many scenarios, which we otherwise wouldn’t be able to do.” In classrooms at LKCMedicine, AR is being used as an interactive teaching tool that could stimulate and garner interest in students’ learning. LKCMedicine Head of Anatomy Assistant

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0 head(set) on Professor Sreenivasulu Reddy Mogali and Associate Professor of Human and Microbial Genetics Eric Yap are developing the MagicBook, an AR app that allows students to use their smart devices to scan markers from anatomy textbooks and worksheets, which pulls out augmented specimens right before their eyes. “There is now a gap in the system where students have access to these materials in the lab, but the access is limited,” said Asst Prof While we welcome the Reddy. “The idea of the app is to promote Fourth Industrial Revolution self-directed and mobile learning, and to have authentic materials for the students with open arms given its to prepare themselves outside of their advantages and endless classes.” possibilities, there is always The app has features such as the nagging doubt that these personalised annotations, labels and interactions curated by Asst Prof Reddy new technologies could for the class. This allows students to interact with the specimens, learn from ever be perfect. explanations given in the AR diagrams of different anatomical parts and even see how it looks like in different medical scenarios. “Perhaps one day, VR and AR could replace cadavers that date back to medieval times, and plastinated specimens which can be costly!” added Assoc Prof Yap.

Welcoming IR 4.0

While we welcome the Fourth Industrial Revolution with open arms given its advantages and endless possibilities, there is always the nagging doubt that these new technologies could ever be perfect. History has taught us time and again that technologies can be used and abused by humans, as seen from last year’s incident when cyberterrorists used technology to hack into the personal information of 1.5 million SingHealth patients. Knowing this all too well, NTU ensures that there is strategic vision and a measured, preventative action plan. Back in February, Prof Suresh also announced three new initiatives, including a new institute called the NTU Institute of Science & Technology for Humanity, which will study the impact of technological revolution on society. The new institute will synergise and coordinate activities at the intersections of technology, natural sciences, social sciences, arts, policy, regulation and governance, business, medicine and ethics across the entire university. With many institutes and centres in NTU dedicated to developing and using AI, VR and AR to their maximum potential, NTU looks set to be at the forefront of Industry 4.0.

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PARTNER

Leading the dementia fightback

In conversation with Paul Matthews Andrew Czyzewski Staff Editor Central Faculty, Communications and Public Affairs Imperial College London

fter leaving Oxford University with a doctorate in Biochemistry, Professor Paul Matthews completed his medical training at Stanford University in the US. It was upon his return to Oxford in the 1990s that he became interested in the brain, through the study of mitochondrial diseases, which can affect both muscle and brain. He developed and applied a range of technologies based around imaging, to probe the molecular events in the brain associated with disease and how they might respond to possible interventions. Prof Matthews’ interest evolved into attempting to understand the molecular links between neuroinflammation and degeneration in the brain, particularly in the context of latelife dementia. This ultimately led to his recent appointment as Associate Director of the UK Dementia Research Institute at Imperial College London (part of a wider national network of Centres). enLighten caught up with Professor Paul Matthews, Edmond and Lily Safra Chair of Translational Neuroscience & Therapeutics and Head of the Division of Brain Sciences in the Department of Medicine at Imperial College London, to find out more about the latest efforts in the fight against dementia EN: Is the UK Dementia Professor Yike Guo (Director of the Imperial Data Science Research Institute really Institute) and Professor Paul Matthews examine large health gearing up now? datasets at the Data Observatory facility PM: There’s always a temptation to say that what one is doing at this moment in time is the most exciting thing one has ever done; but I think in this case it’s genuinely true. The Dementia Research Institute is something that in retrospect I guess I must have been preparing for my entire career, unknowingly. It’s really about trying to pull together a group of people who would not have described themselves as dementia researchers, but who all have a remarkable set of insights and skills into how the brain works. That is a completely new way of thinking. To date, we haven’t done well enough in the way we’ve been thinking about these problems, so we need some new insights. This is an opportunity to create a centre at

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Imperial with neuro-expertise in sleep science; metabolomics; environmental exposure; technology; and inflammation, then bring them all together on the question of how environment and lifestyle influence our risk of dementia. I don’t think there’s any institution in the world that is bringing together exactly this combination of people and facilities. I am confident it will teach us something important. It has the potential to become transformational in its impact. EN: How is big data having an impact on neuroscience? PM: In my opinion perhaps the biggest impact of big data on healthcare would arise from not paying quite so much attention to people who come to the clinic but actually going out and finding those people who aren’t going to the clinics and helping them. With these sorts of data we can immediately begin to illuminate that in silico – we don’t have to do the experiment to get a pretty good idea how that might turn out. It allows us to be more efficient in the way we ask questions; we can ask more important questions and ‘pre-test’ them using the data. Then there are certain sorts of questions we could never answer with conventional means because we could never afford to do them, questions where we need tens of thousands or hundreds of thousands of people in order to arrive at the answers – that is where projects like the UK Biobank present opportunities for capturing data at scale.

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But right now, the challenge we’re facing in the world is that we are generating so much data that there is simply not enough time to look at it all; most is getting lost or is wasted. Some of the most important data for those of us interested in medicine is generated in the health service every hour of every day and more recently through the data being generated by virtue of people using personal technology and apps. So the big data revolution, if there is one, has really just been about the sudden explosion in opportunity for storage and management of data at scale. EN: With several big collaborative projects in neuroscience such as the Connectome Project and Human Brain This is where individual Project taking centre stage, is there still people are needed; thinking, room for small groups and individuals in neuroscience? asking questions and PM: The role of individual creativity is challenging the limits of never going to leave science. The thing ignorance. Science is all about all these big projects is that most of them are fundamentally engineering about individuals. projects – they are about creating a resource. That resource for example might be collecting data on half a million people for UK Biobank or about building a rocket to get to Mars. They involve elements of science but they are not themselves the science. Rather, the science lies in questions you ask of the UK Biobank or what experiments are done when you get to Mars to make the mission worthwhile. This is where individual people are needed: thinking, asking questions and challenging the limits of ignorance. Science is all about individuals. I hope these big projects are merely seen as being empowering.

unique in the world. LKCMedicine already has huge strengths in a number of complementary areas including neuroscience, metabolic medicine and its phenome centre, to name a few. It is particularly interesting to see George Augustine, an internationally leading neuroscientist at LKCMedicine, develop a programme in dementia research at the same time as us, which is funded through the Singapore government and will be exploring very complementary areas. They are launching population studies in Singapore to understand how environmental factors and lifestyle influence the risk of late-life cognitive change in the population’s three ethnic groups, each with a different genetic make-up and potentially different environment exposure, each different again to the UK population. It’s really exciting to see how we can pull these agendas together and use the common elements to drive our science forward faster in both places and use the complementary elements to give us new ideas.

EN: Tell us a little more about how you see research ties with LKCMedicine evolving? PM: I think part of the agenda now is to support the School in developing a strong research component, one that is unique in Singapore and

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PARTNER

Becoming a

clinicianscientist Sean Firoz Assistant Manager Communications & Outreach

aving spent most of their time in clinics and hospitals, clinicians naturally build a sense of curiosity about their medical practice and the care they deliver to their patients. Much like how Senior Resident Dr Chia Po Ying felt while on her residency programme at the Tan Tock Seng Hospital (TTSH) Infectious Diseases department. Dr Chia said, “Practising medicine makes you realise that there are limits to medical knowledge and therapies. The wish to know more and to answer questions that clinical care brings about is the main drive.” However, due to the hectic hours of the medical profession, most clinicians do not have the time or motivation to pursue a research study. Recognising this need, the National Healthcare Group (NHG) has teamed up with Nanyang Technological University, Singapore (NTU) and LKCMedicine to design a Joint Programme for Clinician Scientist Development to train clinicians interested in pursuing relevant research in their field of work. This collaboration was announced at the Singapore Health & Biomedical Congress on 25 October 2018, sealed with a Memorandum of Understanding signed between the two institutions. Guest-of-Honour at the event and Minister for Health Mr Gan Kim Yong said, “With the evolving healthcare needs and demands, I believe the work of clinician-scientists in therapeutic areas such as metabolic, infectious and skin diseases, as well as neuroscience and mental health will become more critical. Clinician-scientists are important bridge-builders between new medical discoveries and their adaptation. NHG and NTU will be

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reaffirming their commitment through the signing of an MOU today to jointly develop and fund clinician-scientists further.”

Help comes in threes

The joint programme comes in three schemes that help all clinicians from residents to senior consultants in NHG institutions start their career in medical research. The NHG-LKCMedicine Clinician Scientist Preparatory Programme (CSPP) is available to clinicians who are Residents or Associate Consultants. This equips them with the right skills and knowledge as they enter in various research fields relevant to their career. Dr Eugene Tan, a Consultant Dermatologist at the National Skin Centre (NSC), was one of the early applicants of the CSPP, after seeing an advertisement about the scheme in 2014. He grabbed the chance to apply for the course, which provided core courses that teach research principles and relevant skills such as writing a grant application and presentation skills for poster presentations.

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Dr Tan said, “I was attracted to that because it was a structured programme with a clear series of modules I can attend, as well as protected time to do both my clinical work and research. I also get to learn different aspects of research like research ethics, protocol and research writing.” When asked about her CSPP experience, Dr Chia said, “The CSPP has great support from the friendly staff at NHG, who come down annually to my department meetings at TTSH to give an introductory talk about the programme from the beginning. The funds available for research is also a definite plus as it allows for a small project that isn’t too ambitious or resource-intensive to kick off.” Residents who apply to the CSPP can also select from three different research tracks: Clinical Research, Translational Research and Health Services Research. The course lasts for up to three years for Residents and up to two years for Associate Consultants. As the research gets more intense and more funding and guidance are needed, the NHG-LKCMedicine Clinician

Scientist Fellowship (CSF) is another scheme that allows clinicians to get hands-on experience in formal research training, such as the PhD by Research programme at LKCMedicine. Slightly different from the CSPP, the CSF focuses more on the PhD projects that these clinicians have applied for, while refining their research skills through a structured programme. Under the CSF, applicants are able to get full sponsorship through the NTU Research Scholarship. CSF applicants are also encouraged to apply for the National Medical Research Council (NMRC) Research Training Fellowship (RTF), which helps them tap into national funding wherever it is possible. And as the clinicians grow into clinician-scientists in their field, the NHGLKCMedicine Clinician-Scientist Career Scheme (CSCS) can help pave their way to a successful research career. The CSCS is designed as post-doctoral scheme that aims to develop the clinicians’ research capabilities further, to contribute in research innovations and improvements in patient care. Apart from a bigger pool of project funds and protected time, the CSCS encourages the clinician-scientist to seek out two mentors from both NHG and LKCMedicine, who will provide them with guidance and expertise in both clinical and research fields. Dr Yew Yik Weng, a consultant at NSC and current third-year PhD student at LKCMedicine applied for the CSCS to pursue a research study on epidemiology. And as part of the scheme, he was encouraged to apply for the NMRC Transition Award (TA) to further build his research career. The NMRC TA provides “Clinician-scientists extra funding for aspiring clinicianscientists to help them transition into a are important bridgestable, independent research career. builders between new Dr Yew said, “For the NMRC TA, I plan to apply with my current project medical discoveries and in LKCMedicine with my current their adaptation.“ mentor, Professor of Cardiovascular - Mr Gan Kim Yong Epidemiology John Chambers and someone from the dermatology side Minister for Health as another mentor who is an expert in eczema. I hope to apply for it soon and improve on it to get the award.”

It’s all about time

Not only do the NHG-LKCMedicine Clinician Scientist Development schemes provide adequate funds and structured training for clinicians to pursue a research career, the amount of protected time to juggle between research and seeing patients is one of the biggest draws for these clinicians. Senior Consultant of Endocrinology at TTSH Asst Prof Rinkoo Dalan is one of the first few clinicians who applied for an earlier version of the schemes. Her foray into research started in 2007, and throughout this time, Asst Prof Dalan appreciated the guidance of the development committee and the protected time she gets from the schemes. “The scheme that I was in, which was equivalent to the CSCS, gave me sufficient protected time, and it was useful because I could dedicate myself to doing research. It also helped that there were people from the (NHG) committee coming down to find out what problems we had and how they can help us get on with things and complete the study,” said Asst Prof Dalan, who is also a recipient of the NMRC TA in 2014. With the help from NHG and LKCMedicine, these aspiring clinician-scientists hope to contribute positively to Singapore’s healthcare system for the betterment of society. “This scheme has given us an opportunity to bring an initial idea to complete publication, which is a big, big process. It is more experiential learning than learning from a book and I am thankful for that,” said Asst Prof Dalan. enlighten ed. 1

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REVIEW

Nipping cancer in the bud

espite the growing repertoire of cancer treatments, patient responses remain varied. In 2018, LKCMedicine Associate Professor Andrew Tan published two papers addressing cancer treatments. ROS release by PPARβ / δ -null fibroblasts reduces tumour load through epithelial antioxidant response, and Targeting nuclear receptors in cancer-associated fibroblasts as concurrent therapy to inhibit development of chemoresistant tumours, were both published in the journal Oncogene. The first study focused on a nuclear receptor, that is implicated in both wound healing and colorectal cancer. In wound healing, PPARβ/δ expression in fibroblasts, which are present in the wound microenvironment, is known to modulate oxidative stress. But its effect in colorectal cancer has not been studied. Tackling this, A/Prof Tan and his team studied the receptor’s role in oxidative stress modulation in colorectal cancer. They found that in mice without the PPARβ/δ gene, experienced reduced oxidative stress. The mutant animals developed fewer intestinal polyps, and survived longer than normal mice. This effect was also observed in human cells, pointing to possible medical applications. A/Prof Tan said, “The tumour microvenvironment (TME) is a major determinant of disease progression and therapy outcomes. The TME is no longer seen solely as a physical support for cancerous epithelial cells, but as an important modulator and even a driver of tumourigenicity.” In the second study, A/Prof Tan turned to cancer-associated fibroblasts (CAFs), the dominant cell type found in tumour stroma. A barrier to developing TME-oriented adjunctive therapy lies in the identification of druggable targets in CAFs, and the validation of drugs. A/Prof Tan said, “The formation of primary, secondary tumors or metastasis is greatly influenced by tumor-stroma interactions, in which stromal cells of the TME, can influence the behavior of the cancer cells. However, current anticancer treatments ignore this supportive role of stromal cells. CAFs are major stromal cells of many tumours. Thus, we hypothesise that targeting them will sensitise tumour cells to conventional chemotherapy drugs.” To tackle this knowledge gap, the team focused on nuclear receptors which are viable targets to suppress CAF-facilitated tumour activity. In this study, they defined the expression profiles of nuclear receptors from human cutaneous squamous cell carcinoma (SCC) biopsies, and identified a cluster of key receptors that have a profound influence on cancer-related activity, such as proliferation, drug resistance and oxidative stress status. A/Prof Tan hopes that his research will lead to improved cancer treatments by enabling scientists to exploit tumours’ dependency on surrounding stromal cells to reveal vulnerabilities of cancer cells. With this understanding, approved drugs could be re-purposed to activate, and repress nuclear receptors to treat other diseases, and shorten the time needed for clinical applications. A/Prof Tan is currently advancing his research in collaboration with China’s Shenzhen Institute of Advanced Technology and Southern University of Science and Technology.

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Sufian Suderman Assistant Manager and Eugene Woon Senior Executive Research Administration & Support Services

ingapore is at war. The enemy? An invisible foe that affects one in nine Singaporeans. In the fight against diabetes, the disease’s complex relationship with an individual’s immune response, has emerged as another factor clinicians and scientists need to consider when delivering personalised treatments. By teaming up across specialties, LKCMedicine’s faculty has designed and developed a novel point-of-care test that can better stratify people who are at risk of earlyonset diabetes. LKCMedicine Assistant Professor Rinkoo Dalan said, “Present stratification strategies and diagnostic tools are inadequate for vascular risk profiling of diabetes patients. They are also difficult to implement in a clinical setting.” In the study — Label-free Leukocyte Sorting and Impedance-based Profiling for Diabetes Testing — published in the journal Biosensors and Bioelectronics in October 2018, Asst Prof Dalan, a clinician-scientist, and Assistant Professor Hou Han Wei, a biomedical engineer from the School of Mechanical and Aerospace Engineering (MAE) and LKCMedicine, developed a novel microfluidic strategy for fast (< 1hour), label-free electrical profiling to determine immune cell activation. They envisioned that this could become a “sample-in answer-out” diagnostic tool for patients with inflammatory diseases, such as diabetes. The study started with Asst Prof Dalan looking for better ways to study vascular biology in diabetes. She was interested in the interaction between blood cells affected by diabetesassociated inflammation, and the blood vessel endothelium, the lining of blood vessels. She suspected that this interplay could affect endothelial activation and long-term arterial stiffness.

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Answering the call to

war against diabetes To help her pursue her hypothesis, LKCMedicine Professor of Metabolic Medicine Bernhard Boehm introduced Asst Prof Dalan to Asst Prof Hou, who had developed a microfluidic platform to measure blood flow and interactions with endothelial cells in vitro. Together, they studied the phenotype of white blood cells in diabetes, and correlated the data with in vivo methods that estimate vascular function and vascular risk factors. “Diabetes, in the chronic state, is really a vascular disease. Micro and macrovascular complications are the main causes of morbidity and mortality in diabetes. Despite advice, attempts to manage patients’ cardiovascular risk factors do not always lead to a complete reduction in risk,” said Asst Prof Dalan. “The personalisation (of therapeutics) can help prevent unnecessary adverse effects of medications, prioritise treatments and increase to cost effectiveness to maximise patients’ benefits,” she said. They found that white blood cells in patients with type 2 diabetes had different electrical, or commonly known as impedance, profiles from nondiabetics. This impedance signature could be used as a novel surrogate biomarker for inflammation, they suggested. Asst Prof Dalan said, “Our clinical findings show leukocyte dielectric properties, such as size and opacity, are associated with cardiovascular risk factors including lipid levels, C-reactive protein and vascular function. These findings will greatly facilitate to increase the understanding of vascular biology in diabetes. Future work includes developing a single chip that can detect multiple biomarkers for rapid point-ofcare testing.” These findings come off the back of another publication by Asst Profs Hou and Dalan earlier last year. Together

with Prof Boehm, they described a novel user-friendly prognostic microdevice for a single-step integrated neutrophil sorting and functional phenotyping from a finger-prick. In diabetes, neutrophils are affected by two innate immune system defence mechanisms. One suppresses their ability to sense and move in response to chemical signals, while the second stimulates these cells to overproduce neutrophil extracellular traps (NETs), which has been associated with tissue damage and delayed wound healing. The team’s microdevice is able to rapidly quantify chemotaxis and NETs formation in a clinical setting.

Currently type 2 diabetes testing is still based on glucose-sensors. There is clinical evidence showing that good glycaemic control is insufficient for managing the disease as other confounding factors exist.

“This device can be translated into risk stratification and precision medicine methods in subjects with metabolic diseases. Currently type 2 diabetes testing is still based on glucose-sensors. There is clinical evidence showing that good glycaemic control is insufficient for managing the disease as other confounding factors exist. Our device can track for chemotaxis (how neutrophils respond to chemical signals), hence revealing protein and lipid metabolism characteristics rapidly and reliably,” said Asst Prof Hou. The team has identified several new candidate biomarkers for type 2 diabetes testing. The next step is to conduct a large-scale clinical study to validate them. This will take place over the next three to five years. The team hopes to further validate these new biomarkers and improve their technology so that it will be cheaper, faster and easier to commercially manufacture. The paper titled A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus was published in Small in February 2018. Collaborating with a clinician has benefitted Asst Prof Hou when designing novel testing platforms. Asst Prof Hou said, “Ultimately, doctors will be the ones using our technologies to help patients. Engineers and doctors are trained differently, so we see the same problem differently. Hence, it is important to work together during the infancy stage of a medical tool development as their feedback and “wish lists” are crucial in driving the research.” enlighten ed. 1

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Lee Kong Chian School of Medicine Headquarters and Clinical Sciences Building Novena Campus 11 Mandalay Road Singapore 308232 Experimental Medicine Building Nanyang Technological University Yunnan Garden Campus 59 Nanyang Drive Singapore 636921 Tel: +65 6513 8572 Fax: +65 6339 2729 Email: ask_lkcmedicine@ntu.edu.sg www.lkcmedicine.ntu.edu.sg

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