Research Output

Total number of patents granted : 14

Total number of patents pending : 16

Spin off company

Jen Wen Pte Ltd, Taiwan

ImmunoBioCare Pte Ltd, Singapore

Development of DNA Vaccine for Asthma and Allergic diseases

We are the first group to demonstrate that allergen gene vaccination approach can result in an inhibition of allergen-specific IgE and Th2 response in mice. This is a novel proof of concept work and our data suggested that DNA vaccination is a feasible approach to prevent and treat allergic asthma and other allergic disorders. We are now studying on the mechanism of DNA vaccination including DNA uptake by dendritic cells, relationship between IgE and CD8⁺ T cells, and the long-term memory immune response elicited by DNA immunization. We will also focus our future research on the optimization of this technology for clinical trials

Development of Mucosal Vaccines for Prevention and Treatment of Allergic Diseases

Approach 1: To explore the use of lactic acid bacteria as a live vector for oral vaccination

Lactic acid bacteria have shown to reduce the Th2 cytokine production from allergic peripheral blood mononuclear cells when re-stimulated with the related allergen. In addition, it can induce the production of regulatory cytokines like IL-10 and TGF-β in the mucosal tissues. These data strongly suggest that Lactic acid bacteria may be useful in the treatment and prevention of allergic diseases.

Approach 2: Production of oral vaccine for immunotherapy in edible transgenic plants

Production of oral vaccine in plants provides a built-in encapsulation system with cell walls and cell membranes protecting the candidate vaccine in the acidic gut environment. Digestion of the plant material may provide a slow release of the candidate vaccine throughout the digestive system allowing presentation to the GALT mucosal immune systems. Therefore, expressing house dust mite major allergen in edible plant is one of the promising delivery systems for mucosal vaccination.

The long-term goal of this research project is to develop oral vaccines for allergic asthma and to study the mechanism of the mucosal vaccination.

Allergen-Based Immunotherapy

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In collaboration with Bioprocessing Technology Institute, we have cloned and fully characterized a panel of 12 allergens from Blomia tropicalis mites. Recombinant mite allergens expressed from the cDNA clones have served as useful reagents for diagnosis and can be further exploited for recombinant allergen-based immunotherapy of mite allergy related asthma and rhinitis.

Allergens array, DNA immunization-induced allergen-specific therapeutic monoclonal antibodies and component-resolved diagnostic and therapeutic reagents using recombinant mite allergens are now being developed. Our laboratory will be collaborating with pharmaceutical companies to develop the immunotherapeutic drugs for asthma and rhinitis.

Allergen-Cell Interaction and Signaling

The mechanisms linking allergic inflammation and neuronal and bronchial airway hyperresponsiveness in allergic asthma are still not well defined. Besides pro-inflammatory cytokines, neurotrophic factors produced by immunocompetent cells such as eosinophils, macrophages, lymphocytes, and dendritic cells can increase nerve excitability and neurotransmitter synthesis. They are likely the mediators of inflammation and allergen-induced bronchoconstriction. Understanding the signaling of allergen-cell interaction will help us to design a better drug in future. The research will focus on the cross-talk signaling between immune and neuro-endocrine system. Animal models for allergic asthma and dermatitis established in our laboratory will be used in this study.

Therapeutic Molecules in Natural Products

Approach 1: Functional characterization of fungal immunoregulatory proteins

We have identified and characterized a potent immunomodulatory protein from an edible mushroom. The potential use of such molecule for cancer immunotherapy and adjuvant of viral and allergen vaccine had been proven conceptually in our laboratory. We will further consolidate the application and mechanistic studies of this immunomodulatory protein, focusing on the human studies.

Approach 2: Identification of novel biomolecules from medicinal plants

This is a new area of our research group. Promising data have been obtained and therefore it could be a potential new direction for the laboratory.

Immunological studies of dust mite allergens

Cheong N, Soon SC, Ramos JD, Kuo IC, Kolortkar PR, Lee BW, and Chua KY (2003). Lack of human IgE cross-reactivity between mite allergens Blo t 1 and Der p 1. Allergy 58:912-920. [PubMed]

Yang L, Cheong N, Wang DY, Lee BW, Kuo IC, Huang CH, and Chua KY (2003). Generation of monoclonal antibodies against Blo t 3 using DNA immunization with in vivo electroporation. Clinical Experimental Allergy 33:663-668. [PubMed]

Ramos JD, Teo AS, Ou KL, Tsai LC, Lee BW, Cheong N, and Chua KY(2003). Comparative allergenicity studies of native and recombinant Blomia tropicalis Paramyosin (Blo t 11). Allergy 58:412-419. [PubMed]

Kuo IC, Cheong N, Trakultivakorn M, Lee BW, and Chua KY(2003). An extensive study of human IgE cross-reactivity of Blo t 5 and Der p 5. Journal of Allergy and Clinical Immunology. 111:603-609. [PubMed]

Ramos JD, Cheong N, Lee BW, and Chua KY (2003). Peptide mapping of immunoglobulin E and immunoglobulin G immunodominant epitopes of an allergenic Blomia tropicalis paramyosin, Blo t 11. Clinical Experimental Allergy 33:511-517. [PubMed]

Cheong N, Yang L, Lee BW, and Chua KY (2003). Cloning of a group 3 allergen from Blomia tropicalis mites. Allergy 58:352-356. [PubMed]

Yi FC, Cheong N, Shek PC, Wang DY, Chua KY, Lee BW (2002). Identification of shared and unique immunoglobulin E epitopes of the highly conserved tropomyosins in Blomia tropicalis and Dermatophagoides pteronyssinus. Clinical Experimental Allergy 32:1203-1210. [PubMed]

Allergen and dermatitis

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Huang CH, Kuo IC, Xu H, Lee YS, and Chua KY (2003). Mite allergen induces allergic dermatitis with concomitant neurogenic inflammation in mouse. Journal of Investigation Dermatology 121:289-293. [PubMed]

DNA vaccine-based immunotherapy of allergic disorders

Chew JL, Wolfowicz CB, Mao HQ, Leong KW, and Chua KY (2003). Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice. Vaccine 21:2720-2729. [PubMed]

Wolfowicz CB, HuangFu TQ, and Chua KY(2003). Expression and immunogenicity of the major house dust mite allergen Der p 1 following DNA immunization. Vaccine 21:1195-1204. [PubMed]

Pharmacology-based treatment of asthma

Duan W, Kuo IC, Selvarajan S, Chua KY, Bay BH, and Wong WS (2003). Antiinflammatory effects of genistein, a tyrosine kinase inhibitor, on a guinea pig model of asthma. American Journal of Respiratory and Critical Care Medicine 167:185-192. [PubMed]

Immunomodulatory protein from natural products

Seow SV, Kuo IC, Paaventhan P, Kolatkar PR, and Chua KY (2003). Crystallization and preliminary X-ray crystallographic studies on the fungal immunomodulatory protein Fve from the golden needle mushroom (Flammulina velutipes). Acta Crystallograph D Biological Crystallography 59:1487-1489. [PubMed]

Paaventhan P, Joseph JS, Seow SV, Vaday S, Robinson H, Chua KY, and Kolatkar PR (2003). A 1.7A structure of Fve, a member of the new fungal immunomodulatory protein family. Journal of Molecular Biology 332:461-470. [PubMed]

Group members

Principal Investigator

Chua Kaw Yan
(PhD; Associate Professor)

• PhD 1984 Massey University, New Zealand.
• Postdoctoral work at the Australian National University, Canberra, Australia.
• 1986-1993 Senior Research Fellow at the Western Australian Research Institute for Child Health, Princess Margaret Hospital, Perth, Australia,
• 1993-1997 Associate Professor at Institute of Immunology, National Taiwan University, Taiwan. Join National University of Singapore since 1997.

Postgraduate studies (MSc and PhD) are available in our Allergy and Asthma Research Program. Please send or email your CV and statement of research interests to A/P Kaw Yan CHUA.

Mailing Address:

Department of Pediatrics, National University of Singapore
5 Lower Kent Ridge Road, Singapore 119074

Laboratory Address:

MD11, #03-14/15, Clinical Research Center,
Faculty of Medicine, National University of Singapore
10, Medical Drive, Singapore 119074

Tel: 65-6874-4344 / 65-6874-4345
Fax: 65-6775-7593
E-mail: paecky@nus.edu.sg