CHEW FOOK TIM
Department of Biological Sciences
National University of Singapore
14 Science Drive 4
Vice Dean (Faculty of Science, Undergraduate Curriculum, Student Life and International Programmes)
Lead Consultant / Scientific Board of Several Major Biomedical / Agri-Businesses
Lab: Lab Website
Allergy and Molecular Immunology Laboratory / Molecular Breeding Laboratory
Lee Hiok Kwee Functional Genomics Laboratories
Main Research Areas
Allergens and Hypersensitivity; Molecular Immunology and Molecular Mimicry, Aerobiology; Epidemiology and Genetics of Asthma, Atopy, Allergic Diseases, COPD, Bronchiectasis, Acne and Related Respiratory and Skin Conditions; Hypoallergenic Vaccines, Auto-allergens and Pan-allergens.
Genetics of Major Crops, Molecular Breeding and Genetic Systems in Plant and Animal Breeding, Large-Scale Plantation-wide Agri-Systems
Our group is interested in understanding the basis of what constitutes an ‘allergen’. We have previously focused on delineating the molecular structure of major allergenic components from dust mites, cockroach, tropical pollen and spores, fungal allergens, as well as unique components from food proteins. This includes identifying, isolating, and cloning the allergenic components; analyzing the antigenic epitopes; and evaluating cross-reactivity between related allergens. We have also explored the use of multiple types of expression systems to produce large quantities of recombinant allergens for structural, biological and immunological studies, and for use in diagnosis and treatment of allergic diseases. Our current focus is to utilize these for Precision Allergology.
We are also interested in understanding the underlying basis of allergic respiratory and skin diseases. We are currently taking a genetic approach to uncover the potential pathways and interactions influencing the pathogenesis and development of these complex diseases. This includes large-scale genome wide association studies, functional candidate gene evaluations, gene-gene (epistasis) and gene-environment studies.
Allergens for Diagnosis, Treatment and Control of Allergies
Type I allergic conditions such as allergic rhinitis, conjunctivitis and bronchial asthma, are a result of an exaggerated production of IgE antibodies against normally innocuous environmental or ingested allergens. In sensitized individuals, allergen exposure induces cross-linking of high-affinity FceRI receptor-bound IgE on effector cells and this would lead to the release of mediators that cause allergic symptoms. Although the mechanisms leading to allergic responses are been extensively elucidated, our understanding of the molecular structures triggering such allergic responses is incomplete. Our research work has focusedmon the high-throughput identification of allergens present in complex allergenic sources; the production, characterization and clinical evaluation of recombinant allergens together with their natural counterparts; and on the elucidation of the exact molecular structures based on molecular modeling, crystallization of the proteins or via Nuclear Magnetic Resonance (NMR) techniques.
The repertoire of antigens acting as allergens thus far covers a wide variety of structural and non-structural proteins, secreted and cytoplasmic proteins, as well as those with or without enzymatic activity, indicating that a vast variety of functionally different proteins are able to elicit IgE responses in atopic individuals. However, many of these allergens turn out to be cross-reactive molecules which belong to highly conserved protein families. From the current data, it seems that the allergen repertoire, although vast, is subject to a large redundancy with many cross-reactive molecules from diverse sources acting in a similar manner. This understanding could contribute to a relative reduction of the number of molecules needed for a highly sensitive and specific diagnosis of allergic conditions as well as for the development of component-resolved desensitization processes via immunotherapy.
We have developed a pipeline of related processes for the rapid identification of allergens; this includes the use of phage display, EST sequencing, full genome sequencing, followed by full length cloning of allergenic components and the use of large scale proteomic identification, bioinformatics analysis and high-density arrays. The strategy has been demonstrated to be highly efficient. To date many different recombinant allergens (more than 200 from our laboratory alone) of various pollens, fungi, mites, insects, food components have been evaluated in more than 10,000 allergic and control individuals from diverse environments. These studies demonstrated that recombinant allergens are highly specific and safe for clinical applications. Recombinant allergens offer a highly specific and safe diagnostic tool to elucidate patient- and disease-specific sensitization patterns which will be needed for the development of patient-tailored immunotherapeutic treatments.
Genetics of Asthma and Allergic Diseases
We initiated a genome-wide association study on atopy and allergic diseases in Singapore in collaboration with the Genome Institute of Singapore (GIS), and Department of Otolaryngology and Paediatrics, National University of Singapore, funded by the Singapore Immunology Network (SIgN). There are clear evidences to support the concept that allergic diseases are influenced by genetic predisposition and environmental factors. In the past decade, studies have shown linkages between certain phenotypes of allergic diseases with markers on >15 human chromosomes. However, variable results were obtained from many previous studies, possibly due to (1) differences in the susceptibility genes for atopy and allergic diseases in different populations; (2) the lack of sufficient statistical power; (3) insufficient coverage of candidate genes and genetic variations within candidate genes due to limited biological understanding of disease; and (4) developmental and environmental differences influencing variations in our susceptibility to these conditions. This proposed project will be carried out by a research team with multiple expertises in clinical allergy, molecular biology and immunology, population genetics, epidemiology, data-mining and integration. The main objectives include the ascertainment of a large clinically and epidemiologically well-characterized demographic-matched case-control cohort which will be recruited to provide sufficient statistical power for identification of major atopic susceptibility genes in our population.
Other Areas of Collaborative Research and Consultancies:
Genetics: Molecular Authenticity, Origins and Traceability of Bio-molecules (e.g., Food, Pharmaceutical Products and Commodities) (Eu Yang Sang); Timber Genetics and Biogeography (Certisource Timber Asia Pacific & Double Helix Tracking Technologies); Functional Genomic Characterization of Oil Palm Traits, Marker Assisted Breeding and Oil Palm Genomics (Sime Darby, First Resources, Genting Plantations, and multiple other Plantations in Africa, Indonesia and Malaysia); Large Scale Plantation-wide Agri Systems (Olam International);
Biomedical Sciences: Cancer (Childhood Leukemia and Breast Cancer); Adipose Derived Stem Cell Biology and Tissue Engineering; Human Secreted Fluid Proteomics; and Biomarkers in Childhood Diseases (NUHS, KKH, Danone Research).
Served as Scientific Consultant / Advisory Board to several companies including Certisource Timber Asia Pacific, Double Helix Tracking Technologies, Sime Darby Technology Centre, Curiox Biosystems, Olam International, First Resources, Genting Biotechnology, Abbott Laboratories, Chairman, Academic Advisory Board for the School of Life Sciences, Management Development Institute of Singapore (MDIS), Governing Board Member of the Southeast Asian Regional Center for Graduate Study and Research in Agriculture (SEARCA) Southeast Asian Ministers of Education Organization (SEAMEO), Governing Board Member of the Southeast Asian Regional Centre for Tropical Biology (BioTrop) Southeast Asian Ministers of Education Organization (SEAMEO), etc.
- Long Service Award 2019, 2014, 2009, 2004 National University of Singapore
- Faculty Teaching Excellence Award 2008, National University of Singapore
- CRISP Award, Outstanding UROPS Project, Faculty of Science, National University of Singapore Faculty
- Teaching Excellence Award – Honour List 2006-7, National University of Singapore
- Faculty Teaching Excellence Award 2005, National University of Singapore
- Singapore Youth Award (for contributions in Science and Technology) 2004
- Tan Kah Kee Young Inventors Award (Biomedical, Open Category) (Merit Award) 2004
- Faculty Teaching Excellence Award 2004, National University of Singapore
- Faculty Teaching Excellence Award 2003, National University of Singapore
- Life Sciences Office (National University of Singapore) Young Investigator Award 2003
- Listed among the 2002/3 NUS Excellent Teachers, National University of Singapore
- Listed among the 2001/2 NUS Excellent Teachers, National University of Singapore
- Outstanding University Researcher Award 1999, National University of Singapore
- Best PhD Thesis in Biomedical Sciences 1998 (Chua Toh Hua Memorial Gold Medal), National University of Singapore
- Young Scientist Award 1997, National University Hospital-National Medical Research Council (NMRC) Singapore
>170+ peer-reviewed scientific publications, >400+ international and regional conference presentations (oral presentations, posters) and >200+ invited talks to-date.
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