Singapore faces a significant challenge with allergic diseases. Currently, up to 20% of school-aged children are diagnosed with asthma and 30% experience eczema (atopic dermatitis). These conditions contribute substantially to the national healthcare expenditure, representing 1.2% of the total healthcare costs, or approximately S$57 million annually.
The Division of Paediatric Allergy, Immunology & Rheumatology, Khoo Teck Puat – National University Children’s Medical Institute, NUH is one of the leading academic research groups in the region. Our accomplishments include over 100 international publications, multiple patents and notable research awards.
In recognition of our international achievements and ongoing contributions to clinical care, research, education and advocacy in Allergy and Immunology, we are recognised as a World Allergy Organisation (WAO) Centre of Excellence.
Our research team specialises in the study of Atopic Dermatitis (AD), Asthma, Allergic Rhinitis and Food Allergy (FA), with a focus on aspects unique to Asia. We research the mechanisms and phenotypes of these conditions, along with their nutritional, psychosocial and economic impacts.
By integrating wet lab and patient-based clinical research, we aim to discover novel risk factors and understand the progression of allergic diseases. This aids in designing treatment and prevention strategies for the Asian Paediatric population.
We carry out research in birth cohorts such as the GUSTO (Growing Up in Singapore Towards Healthy Outcomes) birth cohort, S-PRESTO (Singapore Preconception Study of Long-Term Maternal and Child Outcomes) preconception cohort and the Nutritional Intervention Preconception and during Pregnancy to maintain healthy glucosE levels and offspRing health (NiPPeR) cohort. These cohorts provide opportunities for us to identify risk factors in the preconception, antenatal or early infant phases for the development of allergic diseases later in life.
We are also affiliated with the National AD network and the Asian Skin Microbiome Programme (ASMP), which aims to advance our understanding of the skin microbiome’s role in health and disease, enabling the development of new clinical interventions.
Ongoing clinical trials also form a part of our efforts to assess the efficacy of various allergy interventions.
Our centre collaborates with key leading research institutions and organisations around the world, such as the Murdoch Children’s Research Institute (MCRI), World Allergy Organisation (WAO), European Academy of Allergy and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma & Immunology (AAAAI), the Asia Pacific Academy of Paediatric Allergy, Respirology and Immunology (APAPARI) and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI). We are also key members of international consortia such as the APAPARI Anaphylaxis Registry and the WAO Allergy Prevention Workgroup.
Our key discoveries and contributions include:
We aim to develop novel, precise therapeutic approaches which have significant clinical translational impact in the improvement and/or treatment of allergic diseases, such as Atopic Dermatitis, Asthma and Food Allergy. In addition, we aim to comprehensively assess the prevailing allergy disease burden and its impact on the physical and mental health of Singaporean children and their families. We are also assessing the national economic burden of these diseases to inform and enhance healthcare policies and societal support systems, which could better support families of afflicted children and optimise population health outcomes.
Food Allergy (FA) is a chronic non-communicable disease that typically resolves as children age. It is a major public health concern in western countries, affecting 8% of children and 10% of infants. Unintentional allergen ingestion, due to inconsistent food labeling and a lack of public awareness, leads to severe reactions and considerable psychological distress for patients and families. Our research efforts are centred on enhancing oral immunotherapy (OIT) methods, evaluating their impact on life quality and gut health and formulating strategies to improve treatment outcomes and cost-efficiency in public health.
Food Allergy and Anaphylaxis in Singapore
In Singapore, the incidence of food allergy and anaphylaxis, which is a serious and potentially life-threatening allergic response, appears to be on the rise. Our ongoing research in this area includes evaluation of food allergy and anaphylaxis epidemiology and time trends, risk factors and the broader implications of food allergies on nutrition, well-being and healthcare economics in the region.
Allergy to the prebiotic galacto-oligosaccharide
We have identified an allergy to galactooligosaccharide (GOS), a type of carbohydrate, which is uncommon since most allergens are proteins. This study aims to define the carbohydrate allergen(s) in GOS which consists of a mixture of short chain sugars (known as oligosaccharides) and explore their interaction with immunce cells. Since carbohydrates do not directly stimulate the immune system to produce allergic antibodies (also known as IgE), GOS IgE is likely the result of an immune response from cross reactive glycoprotein(s) (protein allergen with attached sugar branches).
The source of these cross-reactive glycoproteins is also known as the primary sensitiser. This study will also confirm our preliminary data that dust mite, Blomia tropicalis, is the primary sensitiser and that glycoprotein(s) from this dust mite induces antibodies that react to GOS. This research will deepen our understanding of carbohydrate allergies, which till now has been considered to be unimportant. The results will also provide insights into the development of ‘non-allergenic’ prebiotics that are safe for global consumption.
Atopic Dermatitis (AD), a prevalent chronic skin condition in children, is characterised by skin barrier dysfunction, immune imbalance and disruption in the normal skin microbiota composition. In this research, we aim to develop novel microbial-based therapeutics to treat atopic dermatitis, employing bioengineering for microbial modification and strategies to eliminate harmful microbes. The role of the maternal and infant skin, dust and gut microbiome on the development of atopic dermatitis in early life – an integrated multi-omics approach.
We're exploring how irregularities in the skin barrier and immune system regulation in AD, influenced by the skin, gut, and possibly the environmental microbiome, affect the condition. Within the SPRESTO cohort framework, our goal is to disentangle the role of maternal and infant microbiomes and metabolomes on the development of a child’s immune system. We aim to deconvolute the risk phenotypes (microbiome/metabolome biomarkers) that predispose or protect infants from developing AD.
These results would guide the design of cost-effective early life intervention studies to reduce the risk of AD and its related allergic disorders.
Uncontrolled asthma can exacerbate symptoms, leading to a rise in hospital admissions and treatment costs. Often, this is caused by patients incorrectly administering inhaled medications, resulting in less effective treatment and adverse effects. The Whizz clinical trial is assessing whether the Whizz Spacer system can improve the technique and adherence in children using asthma inhalers, compared to conventional valved holding chambers. Our aim is to enhance asthma management and lessen the likelihood of symptom exacerbation.
Our research primarily revolves around the field of genetic epidemiology and genomics, with a particular focus on cardiovascular diseases.
SCADGENS is a multi-ethnic study conducted in Singapore, aimed at understanding the genetic determinants of Coronary Artery Disease (CAD). These are some studies that have concluded with participants from SCADGENS:
In the first CAD GWAS conducted in the Han Chinese population, a susceptibility genetic region in Chromosome 6 was identified. A genetic variant in this region was also found to be associated with increased CAD risk in the Singaporean Chinese population.
This region was later reported to encode a novel protein called androgen-dependent TFPI-regulating protein (ADTRP), which regulates tissue factor pathway inhibitor (TFPI) expression in endothelial cells in an androgen-dependent manner. Our research group is dedicated to elucidating the functional role of ADTRP in cardiovascular diseases. We employ cell lines and animal models to investigate the downstream signalling pathways regulated by ADTRP.
Our clinical researchers in developmental and behavioural paediatrics strive to improve care for children with various developmental disorders. This emerging field in Singapore holds significant promise for policy and practice improvement.
Our clinical-scientists participate in translational neuroscience research to inform early childhood development and clinical care. Beyond descriptive research, we emphasise the need for meaningful interventions that can be employed so as to actively change the paths and outcomes for children with developmental disorders.
Our scientific work has been published in international peer reviewed journals and presented regularly at numerous local and international conferences, winning many awards along the way.
Our work has also improved clinical workflows for children with developmental concerns and is backed by collaborations with national and international bodies. Our doctors have also been involved in various national multi-disciplinary workgroups such as Singapore’s clinical practice guidelines for autism spectrum disorder.
We welcome new collaborations with hospitals and agencies for research.
Our doctors are key members of various collaborative research programmes, and have received competitive research funding from NMRC, Ministry of Health and philantropic organisations (e.g. Lien Foundation, Octava Foundation).
The Child Development Unit (CDU) is a key partner of the Center for Holistic Initiatives for Learning and Development (CHILD) under the NUS Yong Loo Lin School of Medicine. CDU works on projects to enhance developmental screening and support children, especially those from vulnerable communities.
Additionally, CDU partners with CHILD in research activities with local agencies, community organisations as well as international sites. An example of such a study is the HEAlth and Development Support in Preschool Partnerships (HEADS-UPP) study.
Our researchers are involved in the GUSTO birth cohort (Growing Up in Singapore Towards healthy Outcomes), studying factors affecting child development including socio-economic status and maternal mood. This includes examining predictors of developmental outcomes of typically developing children including cognition, executive function and school-readiness. We partner with the GUSTO team in innovative research including the neuroimaging and studying of brain connectivity and profiling of children with neurodevelopmental conditions (BRACO-LD) as co-team members.
Our team members examine various developmental disorders including language and global developmental delays to identify factors associated with varying developmental trajectories in these conditions. These studies will provide insights that help us design effective therapy services and inform us about specific service gaps and patient needs.
Studies in this area include the effects of screen time exposure on children's cognition, behaviour and social emotional development as well as implementation and evaluation of effective interventions to tackle screen time exposure. Research in this area also encompasses looking at family and environmental factors that can have a positive or negative impact on screen time exposure and its consequences.
This programme addresses the unmet needs of families with children affected by chronic medical conditions, as well as understands the cognitive and behavioural profiles of these children. This involves investigating how chronic diseases and their treatments impact child development.
Through this programme, we will establish the overall burden of care to improve resource allocation. This includes children who have overcome haematological cancers, undergone stem cell or bone marrow transplants, live with congenital heart disease post-surgery, were born premature or are managing conditions such as with epilepsy, brain tumours and chronic liver diseases, including those who have received liver transplant.
EF encompasses critical skills such as focus, planning and memory, which are vital for academic achievement. Indeed, EF is a more accurate predictor of academic performance than IQ alone. Our research explores the variables that affect and predict EF, aiming to understand why some children demonstrate stronger EF abilities and the factors influencing these skills.
We also aim to identify the most effective intervention methods to enhance EF in children, including the application of computer-based programs. Notably, our research has identified factors in preschool children ADHD that influence whether ADHD persists into later childhood or improves with age.
Our team conducts research on paediatric endocrinology and diabetes, focusing particularly on paediatric obesity and its associated metabolic complications, including genetics, developmental origins, environmental risk factors and the neurobiology of obesity. Given the rising incidence of childhood obesity and its profound implications for population health and economic impact, this field of research is increasingly important.
Our researchers contribute to the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and Singapore PREconception Study of long-term maternal and child Outcomes (S-PRESTO) cohort studies, exploring the early life risk factors (developmental origins) involved in the development of obesity and metabolic health in later life.
Advances in cancer treatment have improved long term survival after childhood cancer, but often at a price of impaired future fertility due to the use of gonadotoxic chemotherapeutic agents that can cause gonadal dysfunction in prepubertal children. Hence, fertility preservation in young cancer patients may aid in assisting with their fertility in the future.
Our team aims to refine fertility preservation techniques and study how these can be used for assisted reproduction and fertility.
Congenital adrenal disorders (CAD) are a mixed group of conditions that encompasses in-born disorders of the adrenal gland, which produces important hormones for normal bodily functions. Our research involves investigating the genetics of congenital adrenal hyperplasia, which is a form of CAD, assessing the genetic frequency of various genetic errors (mutation) causing CAD, and the clinical manifestations of these genetic errors in the South East Asian population.
The Division of Paediatric Haematology-Oncology provides quality care to children affected by cancer and haematological disorders. Our goal is to develop effective therapies through clinical trials, advancements in haematological progenitor cell transplantation, translational research and international outreach.
We seek to enhance the care of children with cancer in Southeast Asia by blending education, research and clinical practice. The annual St Jude-Viva Forum in Paediatrics Oncology, a combined effort of the St Jude International Outreach Program and the Viva Foundation for Children with Cancer, offers paediatric oncologists in Asia a platform for learning and networking to foster collaborations. The Viva-Asia Acute Leukaemia and the Viva-Asia BMT Working Groups meet at the Forum each year to strengthen regional collaboration and share valuable experiences.
We have implemented a web conferencing system for various purposes, including:
This is the first Chimeric Antigen Receptor T-cell (CAR-T) clinical trial in Singapore, where we will treat high risk B-cell Acute Lymphoblastic Leukaemia (B-ALL) across a span of age ranges, from six months to 80 years of age. This is a cellular therapy trial that aims to treat high risk B-ALL using a number of antigen targets including CD19, CD22 and CD123.
This is the first CD7 CAR-T trial for T-cell Acute Lymphoblastic Leukaemia (T-ALL) in Singapore, where we will treat high risk T-ALL for both children and adults.
Building on the outcomes of the Ma-Spore ALL 2010 (Ariffin et al, JCO 2023; Yeoh et al, JCO 2018) and 2003 studies (Yeoh et al. J Clin Oncol 2012) for children and adolescents with Acute Lymphoblastic Leukaemia (ALL), this new multi-centre study involves NUH and KK Women's and Children's Hospital in Singapore, and the University Malaya and Sime Darby Medical Centre in Malaysia. The Ma-Spore ALL 2010 study uses minimal residual disease (MRD) levels to determine early response to remission induction and tailor the intensity of chemotherapy.
This multi-centre study for children and adolescents with Acute Myeloid Leukaemia (AML) involves the same institutions participating in the Ma-Spore ALL 2010. It uses a modification of the MRC AML 10 treatment back bone replacing the second anthracycline block with high dose cytarabine in efforts to avert cardiotoxicity. It relies on MRD quantitation by flow cytometry and newly identified markers to assess response and select treatment intensity.
This study uses multi-agent chemotherapy, cisplatin, doxorubicin, high dose methotrexate, ifosfamide with etoposide for metastatic patients, and limb salvage surgery with biological materials (host bone) or prosthesis.
This study uses super-selective intra-arterial (ophthalmic artery) chemotherapy in the treatment of advanced intra-ocular retinoblastoma, Reese Ellsworth (RE) IV & V or International Intra-ocular Retinoblastoma Classification (ICIR) C, D & E.
Mononuclear cells from bone marrow of patients on the Ma-Spore ALL 2010 and AML 2010 studies are interrogated using whole genome gene expression profiling and newly discovered algorithms to determine its value in disease subgrouping and prognosis.
We interrogate the immune profile (immunophenotype, RNAseq, TCRsequencing, single-cell RNAseq) of patients undergoing therapy for acute leukaemias and cellular therapies to determine their correlations and influence on outcomes.
Utilising our extensive expertise in MRD monitoring and advanced instrumentation, we are validating recently discovered markers of MRD studies by flow cytometry in ALL and AML for both paediatric and adult patients.
This research assesses the impact of gene mutations and pharmacogenetics on treatment outcomes in paediatric ALL. We have observed that genetic ancestry impacts molecular subtypes of ALL, affecting patient outcomes. Consequently, we are examining ethnic disparities in treatment toxicities and responses. Our research extends to the pharmacogenomics of thiopurine metabolism, specifically the genes TPMT and NUDT15, in Asian populations.
Additionally, we are studying Thiopurine Methyltransferase (TPMT) and Catechol-O-methyltransferase (COMT) polymorphisms in paediatric patients with solid tumours who have undergone cisplatin therapy, correlating the findings with those of audiometric testing.
We have developed unique methods to expand and activate NK cells, as well as to redirect NK cells and T lymphocytes via genetic engineering. Adapted for clinical application, these methods are now being applied to treat a spectrum of malignancies in both paediatric and adult patients. Our lab continues to explore novel strategies for redirecting immune cells and enhancing their anti-cancer capabilities.
Three cell therapy-based clinical protocols have been approved by NUH and Singapore General Hospital ethical boards, as well as the Health Science Authority of Singapore. These protocols deploy expanded allogeneic NK cells to treat patients with various malignancies, including AML, myelodysplastic syndrome, T-cell ALL, sarcoma and neuroblastoma.
We partner with St Jude Global to develop protocols and guidelines tailored for the developing world and lower-middle-income countries, such as the Adapted Resource and Implementation Application (ARIA) protocols, which address specific tumour types.
Additionally, we host Pre-Forum Workshops targeted at our colleagues in the developing nations of the region. These workshops have historically focused on devising effective protocols for leukaemia and solid tumours in resource-constrained countries, as well as enhancing palliative care, developing hospital registries, bolstering supportive care and streamlining fundraising efforts.
Through a joint effort with St. Jude Children's Research Hospital, we have established a twinning partnership with the Southern Philippines Medical Centre (SPMC), serving as a government referral centre for Mindanao. We have also developed a Retinoblastoma Program on Mindanao Island, in collaboration with Dana Farber Children’s Hospital Cancer Centre and St. Jude Children’s Research Hospital, and supported by the Khoo Teck Puat Foundation and the Viva Foundation for Children with Cancer.
This initiative is dedicated to facilitating early diagnosis through educational outreach and establishing SPMC as a referral centre.
Development of laboratory approaches to study immune recovery of patients who received any of these:
MRD-based intervention in patients eligible for advanced cellular therapy and/or BMT, aimed to improve pre-BMT disease status and/or post-BMT disease control.
Philanthropic supported clinical research programmes in:
Since 2022, our centre has been a contributing research entity affiliated with the National Marrow Donor Program (NMDP) in the USA and the Centre for International Blood and Marrow Transplant Research (CIBMTR), also based in the USA.
Our research encompasses both clinical and laboratory studies aimed at improving the understanding of kidney diseases prevalent in Asia. Our goal is to refine diagnostic procedures and treatment modalities tailored to the unique characteristics of our population. Our group’s research output includes over 100 publications in medical journals, more than 300 presentations at medical conferences and the receipt of more than 20 awards for research at regional and international levels.
The Paediatric Renal Immunology and Genetics Laboratory is a specialised branch focusing on the genetics and immunological aspects of kidney diseases affecting Asian children and adolescents.
Our genetics research arm performs genetic assessments for patients with primary glomerular disease using advanced techniques, conducted in collaboration with scientists from the Agency for Science, Technology and Research (A*STAR) and the National University of Singapore (NUS).
Our preliminary studies have revealed that the genetic makeup of Asian populations shows considerable variance from that of Caucasian counterparts. Such genetic insights can potentially guide clinicians in customising medical treatments to the individual needs of patients.
Immunology Research
Our immunology research arm focuses on nephrotic syndrome, mainly minimal change nephrotic syndrome and focal segmental glomerulosclerosis, conditions whose underlying mechanisms are still not fully understood. Our group was the first to describe the role of interleukin-13 (or IL-13) in nephrotic syndrome relapses in children. We have also developed an IL-13 overexpression animal model of nephrotic syndrome to deepen our understanding of the molecular pathways that may be involved in the disease’s onset.
Our latest work has identified the immunological abnormality in children with a serious form of nephrotic syndrome, namely focal segmental glomerulosclerosis, which predicts their response to anti-B lymphocyte monoclonal antibody therapy. This advancement enables more effective treatments to thwart the progression to kidney failure and holds promise for the development of new targeted treatments for this condition.
Our clinical research arm focuses on the diagnosis and prevention of early cardiovascular disease in children with chronic kidney disease. Our approach includes the use of novel biomarkers, ambulatory blood pressure monitoring and specialised imaging techniques to assess cardiac and vascular health.
The DRAGoN Study: Deciphering diversities: Renal Asian Genetics Network
Research into the genetics of renal diseases within Asian demographics has been relatively unexplored. Evidence suggests that the genetic causes of glomerular diseases in Asia differ from other parts of the world. For example, Asian children diagnosed with sporadic steroid-resistant nephrotic syndrome have a much lower prevalence of podocin mutations compared to Caucasian and Middle East patients.
Establishing a dedicated network to study Asian genetics is crucial for a more comprehensive and systematic investigation into the unique genetic profiles of Asian populations, particularly among Malays, who have a higher risk of renal failure yet largely understudied globally.
Our mission is to advance our understanding of the demographics, causes and genetics of glomerular diseases among Asian populations, and eventually to provide an evidence base that not only informs clinical management but also paves the way for the development of novel treatment strategies for genetic-based diseases. We envision a network that will facilitate a systematic study of the renal disease genetics across Asia.
This study is divided into two parts, namely Genome-wide association studies (GWAS) and Next Generation Sequencing (NGS).
Genome-wide Association Studies (GWAS)
This aims to identify genetic risk alleles that may be important in disease susceptibility in primary sporadic FSGS in Asia.
Only a single collection of blood or saliva is required and this can be performed during visits to their doctors. Saliva will be collected either by asking the subject to spit into a cup, or by using absorbent sponges.
By possibly identifying genetic causes of the disease, it may lead to more tailored treatment strategies, which may translate to decreased side effects and lower healthcare costs. Identification of risk alleles for the FSGS in Asia may allow the estimation of lifetime risks for kidney disease, as well as the possibility of response to therapy and risk of disease progression.
Apart from the standard risks involved in blood-taking, there are no additional risks.
We welcome collaborators from healthcare institutions in Asia. If you are a clinician or researcher and would like to find out more about this study, please email Dr Ng Kar Hui at [email protected] for more details.
We cover shipping costs, and provide co-authorship in all publications.
Level 12 NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228
Our research focuses on understanding the molecular basis of human genetics disorders in children as well as leveraging on genetic and genomic knowledge and technological advances to improve the diagnosis and prevention of heritable disorders, in the process developing novel and innovative molecular tests using technology platforms.
Our research focuses on various aspects of neonatology, encompassing both well and ill premature infants. For well infants, we have expertise in developing the cord thyroid-stimulating hormone (TSH) screening for detecting congenital hypothyroidism. This has been successfully implemented in clinical care nationwide.
Our collaboration with the Audiology Department led to development of Universal Newborn Hearing Screening, along with protocols for various at-risk groups. We also worked with the National Expanded Newborn Screening committee to set national standards for metabolic screening using tandem mass spectrometry.
Our ongoing efforts aim to discover and implement novel screening technologies to enhance early detection and intervention, improving the health outcomes of newborns.
Our collaborative research extends to exploring common neonatal conditions such as neonatal jaundice, examining its genetic predispositions and focusing on early detection and treatment.
In maternal and neonatal medicine, we have received grants for investigating the impact of maternal chronic hepatitis B infections on immunoprophylaxis failure of the hepatitis B vaccination programme.
Our studies concerning premature infants include grant-awarded research on the clinical applicability of cranial and vascular ultrasonography. Additionally, we conduct animal research in neonatal haemodynamics.
In partnership with Duke University, we successfully completed a pilot trial in Singapore, assessing the safety and feasibility of autologous cord blood cell infusion in term infants affected by hypoxic-ischemic encephalopathy.
The overarching goal of our research is to translate basic research into a deeper understanding of common neonatal diseases, thereby enhancing the care provided to our most vulnerable patients.Ongoing research of our group includes:
