December 2013 | ISSUE 9
Breaking New Ground: Putting the Spotlight on LKCMedicine's Research Developments




Lisa Li
Assistant Director, Communications & External Relations

In a dim room at the Pancreatic Islet Cell Signal Transduction Laboratory at the Agency for Science Technology and Research (A*STAR), hues of red, yellow, and green are lighting up the confocal microscope’s big screen. Dr Rafael Arrojo e Drigo, Senior Research Fellow from the Lee Kong Chian School of Medicine (LKCMedicine), is keeping a watchful eye on the screen as he talks about the laboratory’s other machine – the new in vivo imaging set-up which arrived in December 2013.

“A lot of earlier studies on rodents don’t pan out in humans,” he says. “But now we have this new ‘toy’ at LKCMedicine which is a laser scanning confocal microscope able to do in vivo imaging for both small and large animals!”

Indeed,  LKCMedicine’s new custom-built ‘toy’ is a world’s first. Visiting Professor Per-Olof Berggren further explains, “We need models that are very similar to the human condition – and that is what we can do now with the new system, which can transplant pancreatic islets into the anterior chamber of non-human primates.”

Staff at the Pancreatic Islet Cell Signal Transduction Laboratory. L-R: Dr Rafael Arrojo e Drigo, Dr Juan Antonio Irondo Diez, Visiting Professor Per-Olof Berggren, Minni Chua, and Dr Xiaofeng Zheng

“Now we have the possibility to study these insulin-secreting cells at single-cell resolution, longitudinally and non-invasively, and that would be the basis of the development of new drugs to treat diabetes,” he says. “I believe that after a 10-year period, we will have enormously exciting results for the diabetic patient.”

Meanwhile, excitement is also brewing over at the Research Techno Plaza (RTP) in Nanyang Technological University (NTU). Professor Bernhard Boehm, LKCMedicine’s Professor of Metabolic Medicine and Director of Metabolic Medicine Research Programme, is explaining his research on immune-mediated diabetes.

“We have developed a system where we have distinct checkpoints so we know which phase of the disease process we are going to interfere with: pre-diabetes, insulitis, or the chronic phase which is characterised by an elevated glucose level,” he says. “The prospects of this research are the rescue of beta cells and what we call the holy grail of immunology – tolerance reduction – which will be very instrumental for a bunch of diseases.”

To achieve these goals, Professor Boehm and his team have been working on the DNA vaccination of both female and male transgenic mice, and to modulate the pace of their diabetes onset. “This is to mimic the different forms of autoimmune diabetes for humans, which afflicts both women and men,” he explains, a unique feature of their research. “Now that we have evidence of the generation of regulatory T cells, the hard work begins. What is the phenotype of these regulatory cells? What is their magic? Can these regulatory cells be expanded? Is there a companion for these magic cells in humans? This is the programme we are going to start here .”

Bernhard Boehm, Professor of Metabolic Medicine and Director of Metabolic Medicine Research Programme

Shaping LKCMedicine’s Research Strategy

Both the laboratories of Professors Boehm and Berggren work on the broad area of metabolic disease, one of LKCMedicine’s key research themes, and part of a broader strategy that has been the work of many over the past two years.

This crafting of LKCMedicine’s research strategy began in March 2011 under the leadership of Founding Dean Professor Stephen Smith. Professor Smith assembled a Research Strategy Advisory Group comprising faculty from Imperial College London (Imperial), namely Professor the Lord Darzi of Denham, Professor Robert Sinden, Professor David Holden and Professor Sir Richard Kitney. The group met in London and outlined the broad strokes of the research strategy. 

Following this initial discussion, Dr Andrew Ang, Director Research Administration and Support Services, facilitated an extensive consultative process with local research stakeholders and expert groups from NTU, National Healthcare Group and its sister hospitals, and A*STAR, with the aim of contextualising and integrating the research strategy to the Singapore research ecosystem as well as the healthcare needs of the community. Subsequently, the School created the first iteration of its research strategy in October 2011, focusing on Infectious Diseases, Metabolic Disease, and Neuroscience and Mental Health, underpinned by Bioengineering and Health Services Outcome Research.

Under the current leadership of Dean Professor Dermot Kelleher and alongside the recruitment of some of our top faculty, the focus of the research strategy has been sharpened. Emphasis is now on the translational and clinical aspects of biomedical research as well as the inclusion of an additional research theme – Dermatology and Skin Biology – along with the cross-cutting technologies of Developmental Biology, Structural Biology, Metabolomics and Sequencing Technologies, and Translational Imaging and Health Services Outcome Research.

To helm LKCMedicine’s research interests, various experts have come on board, including Visiting Professors Per-Olof Berggren, Walter Wahli, Sven Pettersson, Christer Halldin, and Balazs Gulyas who were appointed in 2012 to start various strategic research programmes in islet cell biology, metabolism and gut microbiome, radiochemistry and PET imaging. The first research lab – Muscle and Cardiac Biophysics Laboratory – was set up by Professor of Medical Sciences Michael Ferenczi at RTP. The School’s cross-cutting theme in structural biology was started through the joint appointment of Professor of Structural Biology Daniela Rhodes FRS, with the School of Biological Sciences (SBS).

From left to right: Professor of Developmental Biology Philip Ingham FRS;
Professor of Structural Biology Daniela Rhodes FRS

Since 2013, aside from Professor Boehm, LKCMedicine has also seen the key appointments of Professor of Developmental Biology Philip Ingham FRS, Professor of Cell Biology David Becker, Professor of Infectious Diseases Annelies Wilder-Smith, Professor of Neuroscience and Mental Health George Augustine, and Nanyang Associate Professor Karen Crasta.

A Start-Up Culture

Even with the expertise and collaboration between NTU and Imperial, setting up and establishing LKCMedicine’s research strategy is uncharted territory.

Describing LKCMedicine’s start-up culture, Dr Ng Sean Pin, Deputy Director, Collaborative Research and Contracts says, “LKCMedicine is a new entity so in order to build up our capability, we leverage on the expertise from A*STAR research institutes, work closely with hospitals, and tap on the technology coming from NTU and National University of Singapore, as well as funding by Ministry of Education, National Research Foundation and National Medical Research Council. Externally, we’ll work closely with companies, overseas research institutions and universities including Imperial and Karolinksa Institutet.”

In this light, the funding from private donors has been an act of faith as much as generosity and vision, to help drive LKCMedicine’s research ambitions. In January 2011, the Lee Foundation made a landmark gift of S$150 million to the School, half of which will be used to advance medical education and research, including funding postdoctoral fellowships for research. In February 2013, the Toh Kian Chui Foundation donated S$20 million, with a portion to be used to support a Distinguished Professorship and also medical education and research.

“The trend is towards competitive external funding but we should not view the other research programmes and schools as competition for the same pot of resources,” says Dr Ang. “Instead, we need to see how best we can integrate our expertise collaboratively with the local healthcare and research ecosystem, given the unique resources that we can tap from NTU, Imperial and clinical partners.”

Emphasising the need to support LKCMedicine’s key research faculty in various other ways, Dr Ang adds, “What draws people to collaborate with a research entity is both the core expertise and experience residing in key principal investigators (of the entity) and their long-standing collaborative relationships, as well as the core facilities and infrastructure it can provide.”

To this end, LKCMedicine is committed to providing the resources and administrative support to help the faculty build up competitive research groups that are well integrated with the local research ecosystem and of relevance to the biomedical industry, as well as the larger healthcare needs of the country.

Local and International Collaboration

It is this dovetailing of Singapore’s healthcare needs, research interests and commercial collaboration that has paved the way for a proposed Skin Research Institute of Singapore (SRIS) – the flagship programme of LKCMedicine’s Dermatology and Skin Biology Research Programme. This is a tripartite project between NTU (including LKCMedicine), A*STAR and National Skin Centre, and aims to harness the expertise of scientists, clinicians, engineers and possibly commercial multi-national companies for inter-disciplinary skin research. The three partners have committed close to S$100 million in funding for the project.

Other research groups have also actively sought local collaborations. Professor Ingham and his team are about to embark on a new collaboration with Dr Timothy Saunders in the Mechanobiology Institute at NUS which will employ Single Plane Illumination Microscopy (SPIM) to observe the behaviour of cells in response to different signals in the developing embryos.

Professor Wahli has also started a series of collaborations – on skin health and disease on melanoma progression and metastasis with LKCMedicine’s Assistant Professor Xiaomeng Wang; on the complex epithelial-mesenchymal interactions that take place during wound healing and tumorigenesis with Assistant Professor Andrew Tan from SBS; and collaborative research on insulin resistance in muscle with Professor Ravi Kambadur, also from SBS.

While local tie-ups underpin LKCMedicine’s research, it is also driven by international collaborative links. For example, Professor Wilder-Smith is currently also Lead Principal Investigator and Coordinator of DengueTools, an international research consortium on dengue funded by the European Commission. Following the simultaneous reports in April 2013 of travellers with dengue returning from Angola in South West Africa to six countries on four continents, the DengueTools research team sequenced the virus from Angola and investigated the interconnectivity via air travel between the affected countries. This study culminated in Professor Wilder-Smith’s group publication “Exploring the origin and potential for spread of the 2013 dengue outbreak in Luanda, Angola”, published by Global Health Action in August 2013.

Nanyang Associate Professor Karen Crasta

Meanwhile, Nanyang Associate Professor Karen Crasta has been working with local and international collaborators for her research on anti-mitotic chemotherapeutic drug responses, and the links between genomic instability, cancer and aging. For her efforts, she was awarded the National Research Foundation Fellowship which aims to attract young and promising scientists with funding of up to S$3 million over five years to perform cutting-edge research in Singapore .

Projects in my lab will be done in collaboration with excellent groups within NTU, A*STAR, Harvard Medical School and clinicians in Singapore,” says Associate Professor Crasta. “This is great as I get to avail of unique opportunities that maximise world-class research capable of being done in Singapore and collaborative work with world-renowned labs.”

These plans and efforts are part of a much wider array of research developments by LKCMedicine faculty, in pursuit of greater scientific knowledge for healthcare benefits. And it is clear that beyond the top-notch expertise, high technology, administrative processes and funding needs lies many years of dogged perseverance and passion for their craft.

Back in his office, Professor Boehm leans forward, pointing to the Andy Warhol print on his desk. “I love this sentence by Andy Warhol – ‘Everybody must have a fantasy’. And Albert Einstein said ‘Knowledge is always limited’. So you must have fantasy!”

He breaks into a big smile. “Just think of our experiments. When we started, we had even more questions. Knowledge is still limited – and so you must be open for big surprises.”