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Curriculum vitae

Allergy and Molecular Immunology lab

CHEW Fook Tim (Assistant Professor) Contact Information:  Department of Biological Sciences, Faculty of Science, National University of Singapore, Allergy and Molecular Immunology Laboratory, Lee Hiok Kwee Functional Genomics Laboratories, Block S3, Level 2, Science Drive 4, off Lower Kent Ridge Road, Singapore 117543. Email: dbscft@nus.edu.sg

Main Research Areas:
Allergens and Hypersensitivity; Molecular Immunology and Molecular Mimicry, Aerobiology; Epidemiology and Genetics of Asthma and Atopy; Hypoallergenic Vaccines, Auto-allergens and Pan-allergens.

Research Interests:
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.

Current Projects:
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 focused on 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 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 3000 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.

We have also recently 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 (of 1000 allergic and 1000 non-allergic subjects), which will be recruited to provide sufficient statistical power for identification of major atopic susceptibility genes in our population. An initial phase of whole-genome screening will be conducted with 500 allergic patients having parental family history and 500 non-atopic controls, in order to detect a menu of significantly associated SNPs. Meanwhile, a knowledge-based integration system of data-mining will also be performed to provide a selection of disease-related genes and their underlying interaction networks. A follow-up validation study in another 500 patients and 500 non-atopic controls will be then performed using a list of SNPs that show association with clinical phenotypes. This will be among the first genome-wide screening study in the field of allergy that will help identify key genes or haplotypes that are associated with allergic phenotypes.

Other Areas of Collaborative Research:
Cancer (Childhood Leukemia and Breast Cancer); Adipose Derived Stem Cell Biology and Tissue Engineering; Human Secreted Fluid Proteomics; and Biomarkers in Childhood Diseases (e.g., Kawasaki Disease, Hypersensitivity to NSAIDs).

Recent Awards:

• 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

• Long Service Award 2004, National Unversity of Singapore

• 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

Recent Publications

• Chan SL, Ong ST, Ong SY, Chew FT, MokYK. NMR structure based epitope mapping and modulation of dust mite group 13 allergen as a hypo-allergenic vaccine. J Immunol 2006; 176: 4852-60 .

• Hindley J, Wunschmann S, Satinover SM, Woodfolk JA, Chew FT, Chapman MD, Pomes A. Bla g 6: a troponin C allergen from Blattella germanica with IgE binding calcium dependence. J Allergy Clin Immunol 2006; 117: 1389-95.

• Batard T, Hrabina A, Bi XZ, Chabre H, Lemoine P, Couret MN, Faccenda D, Villet B, Harzic P, Andre F, Goh SY, Andre C, Chew FT, Moingeon P. Production and characterization of pharmaceutical-grade Dermatophagoides pteronyssinus and Dermatophagoides farinae house dust mites for allergy vaccines. Int Arch Allergy Immuno l 2006; 140: 295-305 .

• Hong MLW, Jiang N, Gopinath S, Chew FT. Proteomics technology and therapeutics. Clin Exp Pharmacol Physiol 2006; 33: 583-8.

• Kumar S, Ong SH, Ranganath S, Ong TC, Chew FT. A rule-based approach to robust clump splitting of environmental spores and pollen images. Pattern Recognition 2006; 39: 1088-98 .

• Leong DT, Khor WM, Chew FT, Lim TC, Hutmacher DW. Characterization of osteogenically induced adipose tissue-derived precursor cells in 2-dimensional and 3-dimensional environments. Cells Tissues Organs 2006; 182: 1-11.

• Zuraimi MS, Tham KW, Chew FT, Ooi PL. Indoor Air Quality (IAQ) and respiratory symptoms among children in tropical Singapore child care centers employing different ventilation strategies. Indoor Air (in press).

• Tham KW, Zuraimi MS, David Koh, Chew FT, Ooi PL.  Associations between home dampness and presence of molds with asthma and allergic symptoms among young children in the tropics.  Pediatr Allergy Immunol (in press).

• Leong DTW, MC Abrham, SN Rath, TC Lim, FT Chew, DW Hutmacher . Investigating the effects of preinduction on human adipose derived precursor cells in an athymic rat model. Differentiation 2006; 74: 519-29.

• Leong DTW, Gupta A, Bai HF, Wan Q, Yoong LF, Too HP, Chew FT, Hutmacher DW. Absolute quantification of gene expression in biomaterials research using real time PCR. Biomaterials 2007; 28: 203-10.

• Kumar S, Ong SH, Ranganath S, Chew FT. A contrast-invariant edge-similarity measure using hyperbolic tangent filters to differentiate pollen and spore particulates in environmental captured images. IEEE Transactions on Pattern Analysis and Machine Intelligence 2006; 28: 2042-8.

• Gao YF, Wang DY, Ong TC, Tay SL, Yap KH, Chew FT. Blomia tropicalis, Blo t 21. J Allergy Clin Immunol (in press).

• Component specific IgE in the diagnosis of allergic disease in childhood: more of the same or something more?  Isreal Med Assoc J - Harefuah (invited article).

• Reginald K, Tan CL, Ong TC, Kapoor S, Yap VB, Yap KH, Goh SY, Yuen L, Chen S, Chew FT. Identification and characterization of Der f 22, a novel allergen from Dermatophagoides farinae: a paralogue of Der f 2. (re-submitted).

Updated: April 2007