There is an epidemic of obesity and related disorders, in particular type 2 diabetes, engulfing the world. To develop preventive measures and effective therapies, a clearer understanding of the genetic predisposition, environmental influences, and the cellular and molecular mechanisms underlying disease progression is urgently needed.

 

The establishment of the Singapore Phenome Centre, as well as a Diabetic Biobank (LKCMedicine/TTSH), will allow analysis of the link between genetic and phenotypic variation at the level of the metabolome, as well as interaction with the microbiome (LKCMedicine/SCELSE), whose importance in modulating host metabolism, signal transduction and inflammatory responses is only now beginning to be appreciated.

 

These clinically based studies are complemented by research in model organisms on fatty acid and lipid metabolism, and pancreatic islet cell biology and pathology. The latter exploits a unique in vivo imaging approach whereby islet-cell function and survival can be studied non-invasively, longitudinally and at single-cell resolution. The establishment of this technique at LKCMedicine provides opportunities to analyse non-human primate islet function in models of metabolic disease that are unparalleled anywhere in the world.

 

Development of new therapies for neurodegenerative and psychiatric disorders requires a better understanding of the genetic basis of these diseases. Studies of the genetic component of psychiatric illnesses are complemented by clinical and neurocognitive characterisation of psychiatric symptoms and disorders at IMH. In addition, the Singapore Phenome Centre presents new opportunities to explore the microbiota-gut-brain axis in psychiatric disorders.

 

Identification of novel biomarkers for earlier detection and ultimately prediction of neurodegenerative diseases is an LKCMedicine priority, underpinned by world leading expertise in PET imaging. The availability of such biomarkers will enable monitoring of therapies designed to stop, slow or reverse neurodegeneration, as well as generating new approaches to patient population stratification, allowing more effective targeting of therapy and providing highly profiled cohorts for clinical trials.

 

There are clear opportunities for synergy between LKCMedicine and SBS, especially through interaction with the members of the Warwick-NTU neuroscience partnership, and with the NTU SCE, which has valuable expertise in image data processing and analysis, and neural network analysis and simulation.

 

Increasing microbial resistance to commonly used drugs and the emergence of novel viral strains pose a growing threat to global health. As with the other disease themes, a key approach to this problem is genetics-based, taking advantage of Singapore’s unique population structure and its exposure to specific pathogens such as Dengue virus.

 

The genetic factors that mediate pathogen transmission within host populations, as well as the role of interaction between invading pathogens and the host microbiota in the progression of infection, will be identified. Another important approach will be epidemiological analysis and transmission surveillance of infectious agents, such as Dengue virus and Plasmodium , as well as the design and implementation of vaccine trials.

 

A second focus is to use structure-driven high throughput screening to identify and develop small-molecule inhibitors for the treatment of drug-resistant tuberculosis, hospitalacquired infections due to Gram-negative bacteria, and Dengue virus infection. These studies will also contribute to vaccine development.

Recent rapid advances in our knowledge of skin physiology and disease mechanisms, coupled with major technological breakthroughs, have enabled selective targeting and improved treatment of skin diseases, and the development of novel methods of treating skin wounds, such as burns and non-healing ulcers. LKCMedicine’s major research focus in this area is on wound healing, especially nonhealing leg ulcers, a major complication of diabetes.

 

The innate immune system’s role in wound healing and the skin’s response to microbes is also being investigated, together with the impact of biofilms and their effects on wound healing (LKCMedicine/SCELSE). Other active areas of research include basal cell carcinoma, lymphoma, and inflammatory and immune skin disorders. ​

 

The disruption of genome integrity has multiple consequences, giving rise to a variety of human diseases, including those of the central nervous system, the skin and musculoskeletal system, as well as to premature ageing and cancer.

 

Research in the Nanyang Institute of Structural Biology (SBS/LKCMedicine), focuses on understanding the function of telomeres and telomerase at the molecular level. Telomeres protect the ends of eukaryotic chromosomes from inappropriate DNA repair and also control the terminal replication of chromosomal DNA. More than 90% of human cancers reactivate telomerase, the enzyme that repairs telomeres, as a prerequisite for unrestrained proliferation.

 

Solving the three-dimensional structure of telomerase at high resolution will shed light on the mechanisms of its enzymatic activity and recruitment to telomeres and underpin the design of clinically relevant telomerase inhibitors.

 

Developmental biology has revolutionised biomedical science over the past three decades, providing unprecedented insights into pathological processes, and pioneering the stem cell techniques used in cell replacement therapies. In addition, models of human disease in organisms such as the fruit fly Drosophila and the zebrafish Danio rerio are now well accepted.

 

LKCMedicine has world-leading expertise in the analysis of key intercellular signalling systems, particularly the Hedgehog (Hh) pathway. Such research will continue to inform the development of tissue engineering and cell replacement therapies.

 

The use of zebrafish for high-throughput drug screening is gaining considerable momentum worldwide. LKCMedicine plans to develop models of infection, inflammation, behavioural disorders, metabolic, neurodegenerative and skin diseases to provide the basis for screens of FDA-approved drugs, as well as uncharacterised chemical libraries. ​

Developing early detection and therapeutic treatment for diseases will require a multidisciplinary systems approach that spans various aspects of the research spectrum, from “omics” studies of disease risk factors and epidemiology to diagnostic and rehabilitation technologies and health services outcome research. We bridge the research between healthcare costs and therapeutic treatment and rehabilitation through the cross cutting research theme in health services and outcomes research. We are developing health services outcome research, specifically on population health measurement and innovative models of healthcare delivery such as community health programmes for eldercare, end-of-life management and health financing. Our research is inherently inter- and transdisciplinary and we work with partners from NTU and other key institutions in Singapore’s health system, in particular the National Healthcare Group.

 

The Health Systems & Population Health theme led by Assoc Prof Josip Car aims to build a world-class research programme that will help innovate health systems not only in Singapore but around the world, based on the three forces of healthcare change: personalisation, integration and industrialisation.​​​​

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The Family Medicine and Primary Care (FMPC) team at LKCMedicine is a multidisciplinary group with expertise in general practice, gerontology, psychiatry, social science, psychology and statistical studies. Our mission is to deliver high-quality research designed to improve clinical, managerial and policy decision making for the benefit of patients, families and communities in Singapore. We support and promote the involvement of patients and the public in health research, and are working towards developing a Patient and Public Involvement Group.

FMPC’s research revolves around three highly relevant areas in the delivery of primary care in Singapore:

FMPC places major emphasis on advancing research methodology, and hosts the Primary Care Research Network to encourage and support high-quality research in family medicine in Singapore. It also hosts the Centre for Primary Healthcare Research and Innovation, a joint initiative between LKCMedicine and the National Healthcare Group.