Allergy Asthma and Immunology Research
Research Theme
Immunopathogenesis of asthma and allergies towards advances in diagnostic and immunotherapeutic modalities.
Programme Activities
- Collaborative research on the study of allergen NMR structure with The Institute of Biomedical Sciences, Structural Biology Division, Academia Sinica.
- Collaborative research project on Production of oral vaccine for immunotherapy in transgenic plants with Professor Yu Su-May from Institute of Molecular Biology, Academia Sinica, Taiwan.
- Initiation and coordination of the regional multi-centre Epidemiological studies of mite allergy in patients with asthma/rhinitis.
- Collaborative research with University of Otago, Dunedin New Zealand and Gadjah Maja University, Yogyakarta, Indonesia to carry out a comparative study of gut microbiota between urban Singapore and rural Indonesian (Yogyakarta) toddlers and determine its relationship with the development of allergic diseases.
- Collaborative Research initiative on the protective effects of probiotics on allergic disease encompassing a double blind placebo controlled randomized clinical trial on the protective effects of probiotic supplementation in newborn infants, in-vitro study of the underlying immunoregulatory mechanisms of probiotics, and the protective/therapeutic potential of probiotic bacteria expressing recombinant dust mite allergens as a vehicle for allergen immunotherapy in mouse dust mite allergy model.
- Joint South East Asian studies on the epidemiology food allergy and allergic diseases in the young children in Singapore, Thailand and Indonesia.
- Weekly journal club and biweekly research seminars.
- Medical and Polytechnic attachment students working on research projects.
Research Projects
- Mechanism of the pathogenesis of allergic diseases, focus on allergen and cell surface molecules interaction in skin fibroblast, lung epithelial, DC, Treg and B cells.
- Therapeutic and prevention modality with respect to studies on:
- DNA vaccine,
- Oral vaccine,
- Recombinant allergens-based immunotherapy, and
- Development of new adjuvant for vaccines.
- The influence of environmental factors in the development of childhood allergies:
- A clinical trial on the effects of probiotics on atopic disease in babies at risk for atopy. The aim of this study is to assess the effect of early and sustained feeding of probiotics on the subsequent development of eczema and sensitization to allergens.
- A prospective study to compare the gut microbiota between two populations, one with high prevalence of allergy (Singapore) and one with low prevalence (Indonesia) in the first two years of life.
- A cross-sectional, population survey on the prevalence of food allergy in Singapore, Thailand and the Philippines.
- Comparative study on allergen sensitization in young children in Singapore, Jakarta and Bandung.
- A follow up cohort study on infantile wheezing to assess risk factors for persistence of wheeze.
- A population survey on drug allergy in Singapore children to assess prevalence and trend.
- A study on the effects of cold drinks on asthma symptoms.
Member(s) of Programme
Programme Coordinators:
Adj Assoc Prof Lee Bee Wah
Prof Chua Kaw Yan
Members:
Prof Van Bever, Hugo P S
Assoc Prof Wang De Yun (Dept of Otolaryngology, NUH)
Dr Lynette Shek Pei Chi
Dr Cheong Nge
Dr Liew Lip Nyin
Dr Seow See Voon
Dr Huang Chiung Hui
Dr Yi Fong Cheng
Dr Xu Hui
Ms Seah Ching Ching
Ms Teo Su Min, Audrey
Mr Soh Gim Hooi
Ms Tan Teng Nging
Ms Liew Lee Mei
Mr Mah Ka Weng
Ms Wen Hong Mei
Ms Or Ming Yan
Ms Wong Wen Seen
Ms Ding Ying
Ms Judy Anthony
Ms Kwek Poh Lian, Corinne
Gerontology Research Programme
Research Theme
Healthy and productive aging.
A systematic and coordinated programme of research activities on the health of the elderly population in Singapore, it aims to help the understanding of the population aging transition and provide the scientific information needed for formulating strategies of disease prevention and health promotion.
Themes
- Functional disability: prevalence, trends, risk factors, healthcare and social service needs.
- Cultural-linguistic bias in test and item performance in ADL, IADL, GHQ and MMSE.
- Dementia and cognitive impairment: prevalence, risk factors, impact.
- Mild cognitive impairment and early dementia: screening instruments.
- Nutritional factors, neurocognitive functions, dementia.
- Depression in old age: prevalence, risk factors, somatization, subsydromal depression, vascular depression, nutritional factors.
- Exercise and cognitive enhancement: randomized controlled trial.
- Health care utilizations of elderly: impact, predictive factors.
- Community-based Early Psychiatric Interventional Strategy (CEPIS): randomized controlled trial.
- Longitudinal study of cognitively normal elders relating brain structure, function and cognition.
- Singapore-Sweden Collaborative Study of Cultural Differences in Aging.
- Hospital readmissions, mortality and quality of life of COPD patients and their predictors.
- Cognitive impairment, depression and functional outcomes of stroke patients in community hospital care.
Member(s) of Programme
Programme Coordinator:
Assoc Prof Ng Tze Pin
Members:
Prof Kua Ee Heok
Prof Victor Goh (O&G)
Assoc Prof Tan Chay Hoon (Pharmacology)
Assoc Prof Calvin Fones (Psychological Medicine)
Assoc Prof Ko Soo Meng
Collaborators:
Dr Gerald Koh (COFM)
Dr Steve Graham (Psychology)
Dr Angelique Chan (Sociology)
Dr Tomasina Oh (English Language and Literature)
Assoc Prof Michael Chee (SingHealth Cogntive Neurology Laboaratory)
Dr Donald Yeo (Neurology, SGH)
Dr Philip Eng (Department of Respiratory Medicine, SGH)
Dr Ong Kian Chung (Department of Respiratory Medicine)
Dr Yap Keng Bee (Department of Geriatric Medicine, AH)
Dr Mahadevan Sahadevan (Department of Geriatric Medicine, TTSH)
Dr Sitoh Yih Yeh (Department of Geriatric Medicine, TTSH)
Dr David Yong (Ang Mo Kio Community Hospital)
Dr Fong Ngan Phoon (St Luke's Community Hospital)
Dr Tan Booon Yeow (St Luke's Community Hospital)
Prof Bengt Winbladt (Karolinska Institute, Sweden)
Research Personnel:
Dr Mathew Niti, Research Fellow
Susan Hin Hiang, Projects Administrator
Pang Mingyi, Research Assistant
Helicobacter Pylori
Research Theme
To identify molecular mechanisms of pathogenesis of Helicobacter Pylori and improve treatment.
Specific Themes
- Molecular mechanisms of H. pylori pathogenesis.
- The use of probiotic/prebiotics as alternative therapeutic strategy.
Programme Activities
- Molecular mechanisms of H. pylori pathogenesis
- A cytoplasmic enzyme 1 (CE1) has been identified to be strongly associated with patients having peptic ulcer disease (p<0.001). Purified native CE1 exhibited significantly higher cell apoptosis inducing activity (p<0.05), induces H2O2 generation and elevated interleukin-8 production by activating NF-KB in gastric epithelial cells. These findings show that CE1 may play an important role in the pathogenesis of H. pylori-associated severe gastric diseases (unpublished data).
- Another surface localized enzyme (SE1) was shown to interact with CagA by co-IP. It was shown that SE1 acted in concert with CagA affecting the tight junction protein, ZO-1 of T-84 and AGS cells. A comparison study of cagA+, cagA- and isogenic mutant (SEI knock out) H. pylori strains was performed using confocal microscopy and functional study based on the tracking of leakage of biotinylated albumin across cell monolayer. The results suggest a probable chaperonic role of SE1 in assisting CagA-mediated ZO-1 recruitment, indicating the potential role of SE1 in facilitating H. pylori invasion into the host mucosal, leading to pathogenesis (unpublished data).
- The use of probiotic/prebiotic as alternative therapeutic strategy
- With antibiotic-resistance on the rise over the years, the development of effective alternative therapy is important. Results from the studies of "generally regarded as safe" microalgae and microalgae sulfated polysaccharides show that they are effective in detaching H. pylori from the surface of tissue cultured cells and is bactericidal to H. pylori at concentrations that do not harm tissue cultured cells. It indicates that these 'pro-/prebiotics' may potentially be used as anti adhesive and bactericidal agents.
Member(s) of Programme
Programme Coordinator:
Assoc Prof Ho Bow
Members:
Assoc Prof Yeoh Khay Guan (Dept of Medicine)
Assoc Prof Ho Khek Yu (Dept of Medicine)
Assoc Prof Teh Ming (Dept of Pathology)
Assoc Prof Quak Seng Hock (Dept of Paediatrics)
Human and Molecular Genetics Research Programme
Research Theme
To establish and develop genetic research and diagnostic facilities in cardiovascular, asthma, endocrine, neurometabolic, haematologyoncology, renal and developmental genetics, with regards to:
- Genetic epidemiology, including sequencing, mutation screening, and genotyping.
- Establishment of a cord blood bank resource representative of Singapore's three major ethnic groups.
- Karyotyping and gene mapping by linkage analysis and molecular cytogenetics.
- Molecular diagnostics and gene therapy.
- Functional genomics and pharmacogenomics.
- Animal models of human development and disease.
Member(s) of Programme
Programme Coordinator:
Dr Heng Chew Kiat
Members:
Dr Caroline G Lee
Dr Goh Li Meng, Denise
Dr Lai Poh San
Dr Lee Yung Seng
Assoc Prof Loke Kah Yin
Prof Low Poh Sim
Assoc Prof Quah Thuan Chong
Assoc Prof Quek Swee Chye
Assoc Prof Samuel S Chong
Dr Tay Kiat Hong, Stacey
Prof Yap Hui Kim
Lactic Acid Bacteria (LAB) Interest Group
Research Theme
Intestinal lactic acid bacteria as probiotics and vectors for gene therapy.
Programme Activities
The LAB Interest Group is in collaboration with the following research groups:
- Asthma and Allergy Research Programme, NUS
Development of prophylatic and therapeutic vaccines for asthma and allergy. Immune response to allergens in early childhood in relation to environmental factors.
- Edible Vaccine Group, NUS
Intestinal Colonization and immune-modulation by probiotic microoganisms expressing antigens of pathogens.
- Medical Nutrition Group, Karolinska Institute, Sweden
Host-microbe cross-talk focuses on colon cancer.
- Functional Food Center, Turku University, Finland
Bacterial adhesion and gene expression in human colonocytes: target for probiotic development.
Member(s) of Programme
Programme Coordinator:
Assoc Prof Lee Yuan Kun
Members:
Assoc Prof Bay Boon Huat (Anatomy)
Dr Ratha Mahendran (Surgery)
Dr Tan Hai Meng (Kemin Induestries)
Prof Jimmy Kwang (TTL)
Assoc Prof Ng Mah Lee (Microbiology)
Dr Seah Geok Teng (Microbiology)
Assoc Prof Vincent Chow (Microbiology)
Dr Lynette Shaek Pei Chi (Paediatrics)
Dr Zhang Dao Hai (Molecular Diagnosis Centre, NUH)
Prof Sven Pettersson (Karolinska Institute)
Neuro-Degeneration
Research Theme
To study factors which contribute to, or modulate, degeneration of the nervous system. Research is centered on the calcium hypothesis of aging and dementia, and examines factors that contribute to, or modulate calcium influx into neurons. The role of calcium dependent and free radicals in events leading to neurodegeneration, and the role of glial cells in propagating neuronal injury are also examined. In addition to calcium, an accumulation of iron and cholesterol oxidation products can also be toxic to neurons, and research is carried out, to elucidate iron and cholesterol metabolism in the brain.
Programme Activities
Collaborative projects have been carried out between members of the group, resulting in several papers in premium journals, book chapters, and awards at international conferences. Individual members have also been awarded several grants for research on cell models of neurodegenerative diseases, and translational research, on the development of antioxidants to treat neurological disorders.
Member(s) of Programme
Programme Coordinator:
Assoc Prof Ong Wei Yi
Members:
Prof Barry Halliwell
Assoc Prof Lim Tit Meng
Assoc Prof Benjamin Ong Kian Chung
Assoc Prof Hanry Yu
Neuro-Psychopharmacology
Research Theme
The pharmacology of drugs that may exert neural, psychological and behavioural changes in animals and human.
Programme Activities
- Continuation of studies of the effects of antipsychotics on working memory and fMRI.
- Continuation of studies of the roles of 5-HT receptor subtypes in the effects of antidepressant drugs on adult neurogenesis and stem cell proliferation.
- Studies of antidepressant drugs on glutamate receptor expression in mice.
- Studies of noradrenergic modulation of hippocampo-prefrontal cortical long-term potentiation.
Member(s) of Programme
Programme Coordinator:
Assoc Prof Tan Chay Hoon
Members:
Assoc Prof Peter Wong Tsun-Hon (Pharmacology)
Assoc Prof Lee How Sung (Pharmacology)
Prof Kua Ee Heok (Psychological Medicine)
Prof Calvin Fones Soon Leng (Psychological Medicine)
Dr Zhu Yi-Zhun (Pharmacology)
Dr Gavin Dawe (Pharmacology)
Assoc Prof Ong Wei Yi (Anatomy)
Oxidants and Antioxidants Research Group
Research Theme
To study the molecular and cellular biology of the action of oxidants and antioxidants and their role in human disease and human nutrition.
Member(s) of programme
Programme Coordinator:
Prof Shazib Pervaiz
Members:
Prof Subroto Chatterjee (Johns Hopkins Singapore)
Prof Barry Halliwell
Prof Ong Choon Nam
Prof Malcolm Paterson
Prof Alan Porter
Prof Sit Kim Ping
Prof Roland Stocker
Prof Frank Watt
Prof Philip Keith Moore
Assoc Prof Matthew Whiteman
Assoc Prof Tan Kwong Huat Benny
Assoc Prof Ong Wei Yi
Assoc Prof Kenneth Hughes
Assoc Prof Marie-Veronique Clement
Assoc Prof Urs Alex Boelsterli
Assoc Prof Lim Sai Kiang
Dr Steve Cheung Nam Sang
Dr Jan Gruber
Dr Jeffrey Armstrong
Dr Rajasekhar Balasubramanian
Dr Andrew Jenner
Dr Lee Chung-Yung, Jetty
Dr Peter Colin Rose
Dr Shen Han Ming
Dr Markus Wenk
Dr Wong Boon Seng
Dr Huang Dejian
Dr Ronan Kelly
Singapore Epidemiology of Eye Diseases (SEED) Centre
Research Theme
The Singapore Epidemiology of Eye Disease (SEED) program serves to initiate, promote and coordinate ophthalmic epidemiologic research in Singapore and in Asia.
The program focuses on major eye diseases of unique importance in Asia, such as myopia and angle-closure glaucoma. SEED will focus on epidemiology and biostatistics, and will include research related to clinical, genetic and molecular epidemiology, evidence-based medicine and outcomes research.
Specific Aims
- To determine the prevalence, incidence, risk factors & public health impact of eye diseases in Singapore and Asia through the conduct of epidemiological studies.
- To foster international collaborations with other ophthalmic epidemiology groups in Asia and worldwide.
- To provide research expertise & consultation to other research centers and ophthalmic institutions in Singapore and Asia.
- To conduct training programs for clinicians & research students interested in ophthalmic epidemiology.
- To organize workshops, symposia & international meetings on ophthalmic clinical research and epidemiologic methods.
Programme Activities
- At the core of the SEED program, five large epidemiology studies comprising of more than 10,000 participants are currently ongoing.
- SEED is also involved in acute epidemiological studies, including the recent case-control study on the risk factor for fungal keratitis in contact lens users.
- Summary of all past and present SEED projects are as follows:
| SEED Projects |
Time Line |
Funding Agency |
Population Sample Size |
| Tanjong Pagar Survey |
1997-1999 |
NMRC |
1,232 |
| Sumatra Eye Survey |
2001-2002 |
NMRC |
1,043 |
| Singapore Longitudinal Aging Study - Eye component |
2004-2006 |
NMRC |
2,413 |
Singapore Cohort Study
of the Risk Factors for
Myopia (SCORM) |
1999-ongoing |
NMRC |
1,979 |
| Singapore Malay Eye Study (SiMES) |
2004-ongoing |
NMRC & BMRC |
3,300+ |
Singapore Prospective
Cohort Study (SP2)
- Eye component |
2004-ongoing |
NMRC |
4,500+ |
| Multi-Centre Retinal Stroke Study (MCRS) |
2004-ongoing |
NMRC |
1,000+ |
Member(s) of Programme
Co-Directors:
Assoc Prof Wong Tien Yin
Assoc Prof Saw Seang Mei
Recruitment Coordinator:
Aidah Idris
Clinical Coordinator:
Mya Sandar
Data Coordinator/ Statistician:
Wong Wan Ling
Members:
Assoc Prof Tai E Shyong
Prof Donald Tan
Assoc Prof Aung Tin
Dr Anoop Shankar
Assoc Prof Ng Tze Pin
Prof David Koh
Dr Janice Lee Mong Li
Assoc Prof Wynne Hsu
Tissue Engineering
Research Theme
Repair and Regeneration of Musculoskeletal Tissues
Programme Activities
- Isolation, Culture and Characterization of Mesenchymal Stem Cells (PI: Prof EH Lee)
It has been reported that adipose tissue is an alternative source of MSCs, and that adipose tissue-derived MSCs (AMSCs) are capable of differentiating into multiple lineages. As BMSCs are not so easily obtained, the research group decided to examine AMSCs and compare them with BMSCs. AMSCs and BMSCs were studied in terms of their cell-surface marker expression, their differentiation potential and their expression profiles using a wide range of techniques including flow cytometry, immunostaining, histology, realtime RT-PCR and microarray analysis. These studies showed that surface-marker expression could be used to isolate subpopulations of MSCs with enhanced colony formation capabilities. Expression profiling showed that BMSC and AMSC express many common genes, however chondrogenic differentiation studies showed that BMSCs are superior in inducing chondrogenic differentiation to AMSC.
- Chondrogenic Differentiation of Mesenchymal Stem Cells (PI: Prof EH Lee)
The team has been studying the differentiation of chondrocytes for repair of articular cartilage as well as for repair of physeal or growth plate cartilage. Novel in vitro methods for chondrogenic differentiation of BMSCs are currently being fully characterized and promise to provide tools for unraveling the macro-molecular processes involved in articular and physeal chondrogenic differentiation. In particular, the team has been able to induce MSCs to differentiate into physis-like tissue which contains the many different cartilage cell types found in normal physis. In parallel, conditions for maintaining the stable phenotype of chondrocytes are investigated to obtain cells suitable for transplantation in articular cartilage. In addition, we have developed systems and are studying the effects of various extracellular matrix components on BMSC proliferation and differentiation.
- Tendon and Ligament (PI: Assoc Prof James Goh)
PLLA and PLGA have been extensively investigated as possible materials for ligament tissue engineering applications by the group. However, PLLA and PLGA tissue-engineered tissues demonstrated inferior mechanical properties and rapid degradation rates compared to the normal tissue. The extraordinatory mechanical properties and enhanced environmental stability of silk make silk fibroin (core of silk) to surpass the costly PLLA and PLGA, as potential biomaterial for ligament tissue engineering applications in orthopedic research. To avoid the immune response elicited by the sericin and improve the biocompatibility of silk fibers, the group has modified the sericinfree silk fibers with gelatin and crosslinked with NDGA. The physical properties and biocompatibility of modified silk fibers and native silk fibers were compared using in vitro and in vivo models. A new modified knitted silk scaffold will be tested in vitro and used to reconstruct ACL in rabbit and pig model. In addition, the group has designed a bioreactor to provide cyclic tensile stimulus to enhance orientation of the cells and collagen fibers for engineering ligaments. The system is under debugging.
- Spine (PI: Prof Wong Hee Kit)
In 2005, nine (9) (out of 42) animals (pigs) were operated and sacrificed end of 2005. The samples have been analyzed and the intermediate interest has been concentrated on the improvement of the biomaterial handling including optimized seeding and culturing techniques for the stem cells plus growth factors. Samples underwent micro CT, x-ray, bone density and histological analysis. Biomechanical analysis is in preparation. The investigated animals show an improvement of spinal fusion capability by using our new designed PCL-TCP biomaterial after six months compared to the results of the control group using bone autograft. These short term data have to be confirmed by the long term data and have to be tested for statistical significance.
Member(s) of Programme
Programme Coordinator:
Prof Lee Eng Hin
Members:
Assoc Prof James Goh Cho Hong (Secretary)
Prof Casey Chan
Prof Wong Hee Kit
Assoc Prof Lim Beng Hai
Assoc Prof James Hui Hoi Po
Dr Wilson Wang Ee Jen
Assoc Prof Dietmar Werner Hutmacher
Dr Simon Mckenzie Cool
Research Staff:
Dr Jacqueline Frida Schmitt
Dr Ricardo Rodolfo Lareu
Dr Liu Tongming
Dr Liu Haifeng
Dr Detlef Olaf Alexander Schumann
Dr Yang Kai
Dr Yang Zheng
Bharti Dewangan
Zhao Tianyun
Wu Yingnan
Collaborators from National University Hospital:
Dr Alphonsus Chong
Dr Suresh Nathan
Collaborators from Division of Bioengineering:
Prof Teoh Swee Hin
Assoc Prof Toh Siew Lok
Assoc Prof Michael Raghunath
Assoc Prof Dietmar Hutmacher
Asst Prof Phan Toan Thang
Venom and Toxin Research Programme
Research Theme
From Venoms to Drugs, From Toxins to Therapeutics
Programme Activities
In general, purification, biochemical and pharmacological characterization as well as molecular aspects of research involving cloning, sequencing and expression of new toxins are actively being done by the academic staff with the help of research fellows, research assistants and postgraduate students. A range of novel toxins from different species of scorpions, spiders and cone shells have been isolated, purified, sequenced and the synthetic toxins being screened for novel biological activities. Several channel toxins, specific for sodium, potassium or calcium channels, have been extensively studied with respect to their structure, mode of action, and localization of the functional site. In particular, a programme combining combinatorial chemistry, analogue screening, NMR and molecular docking along with the use of clinically relevant animal models has been implemented for the development of optimized lead peptide with therapeutic potential for rheumatoid arthritis. Crystallographic studies of phospholipase A2 toxin from Daboia russelli siamensis venom have also been done. Antimicrobial peptides against B. pseudomallei have been screened from the venoms and toxins of various species of snake, scorpion, spider, and cone snails. The role of PLA2 as a target in melioidosis and its inhibition by PLA2-inhibitory peptides have been explored along with cytokine gene expression studies in acute infection and in response to treatment with potential bactericidal agents using mouse model and DNA microarray. Establishment of global gene expression profiles of human neuronal cell lines following exposure to sarin is in progress using DNA microarray technology.
Member(s) of Programme
Programme Coordinator:
Prof P Gopalakrishnakone (Anatomy)
Members:
Assoc Prof Khoo Hoon Eng (Biochemistry)
Assoc Prof Tan Chee Hong (Biochemistry)
Prof Kandiah Jeyaseelan (Biochemistry)
Assoc Prof Maxey Chung Ching Ming (Biochemistry)
Dr Zhang Yong (Engineering faculty)
Research Personnel:
Dr Maung Maung Thwin (Research Fellow)
Dr R Perumal Samy (Research Assistant)
Dr R. Saminathan (Research Fellow)
Dr Gao Rong (Research Fellow)
Top