Our data indicate that asthma and allergic diseases are common in Singapore, with up to 20% of schoolchildren with diagnosed asthma. Morbidity of asthma is also substantial in terms of hospital admissions and bed days utilised. The economic burden is considerable, amounting to S$57 million/ annum, and direct costs equivalent to 1.2% of our healthcare bill.
Our research group is one of the pioneers in defining the allergens of this region and has a good track record, with more than 100 international publications in the subject of allergy and immunology, several patents approved and submitted, and awards received. We are therefore poised to face the challenges in this field of research and continue in our pursuit to achieve research excellence, in the following research areas.
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.
Development of Probiotics-based Mucosal Vaccines for Prevention and Treatment of Allergic Diseases
Lactic acid bacteria have been 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. Animal models of allergic asthma and allergic dermatitis are used to explore the effectiveness of wild type and recombinant lactic acid bacteria for oral vaccination. The interaction of gut dendritic cells with the probiotics will be further elucidated to understand the immunomodulatory effects of probiotics on the Th2 immune responses. 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.
Development of DNA Vaccine for Asthma and Allergic diseases
Allergen gene vaccination approach has been demonstrated to result in an inhibition of allergen-specific IgE and Th2 response in mice. This is a novel proof-of-concept work and our data suggest that DNA vaccination is a feasible approach to prevent and control allergic asthma and other allergic disorders. We are now studying on the mechanism of DNA vaccination including DNA uptake by dendritic cells, regulation of Th2 immune responses and IgE production, 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.
Therapeutic Molecules in Natural Products: 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 by performing mechanistic studies related to this immunomodulatory protein.
Comparative evaluation of the bacterial gene composition of stool microbiota in infants with and without eczema
Eczema is common chronic inflammatory skin disorder with significant impact on child health, and its prevalence is increasing worldwide. It is known that the interaction between gut microbes and the host immune system influences early life development of the immune system. We and others have shown that the composition of the stool microbiota signatures differ between eczema and healthy controls in infancy. We hypothesize that the immune dysregulation associated with childhood eczema is influenced at least in part, by the products of certain gut bacterial structural and functional genes e.g. (i) virulence genes and (ii) genes involved in carbohydrate metabolism. We aim to assess the structural and functional gene composition of stool microbiota of 10 infants with eczema and their matched (for age, gender, mode of delivery, feeding) controls at the age of 3 months. The scope of work will include the identification of functional and structural gene composition present in the stools of infants with and without eczema by comparative metagenomics using 454 pyrosequencing.
Characterizations of Innate and T cell Immune Responses and Identification of Biomarkers Associated with Wheeze in the First 24 Months of Life
Early childhood wheezing increases the risk of subsequent asthma. Although the allergic predisposition is an important risk factor for these disorders, our recent studies also show that wheezing in early life could be due to pre-existent immune aberrations in cord blood cells. Our earlier studies have shown that cord blood cells of infants who subsequently wheeze in the first 2 years of life have abnormal heightened responses of the innate compartment of immune cells when stimulated with mitogens (chemicals) in laboratory culture. We therefore hypothesize that these immune cells of the innate immunity could be aberrant in these infants and that this abnormality would lead to an increased susceptibility to lung inflammation which manifests as wheezing disorders. We aim to study and characterize these immune abnormalities in infants with wheezing disorders. We will study in detail the responses of monocytes (specialized cells of the innate immune system) from cord blood and peripheral blood of these infants at 1 year of age and their matched healthy controls. In addition, the subsequent effects on the T helper cells (specialized cells of the adaptive immune compartment) will be studied in the blood of these infants at the age of 1 year. Using molecular techniques and specialized protein array methods, the profile of proteins (cytokines) released by the immune cells of the cord blood and (1 year old) peripheral blood, and their genes expressed will be studied and compared with healthy controls. The findings of this proposal will provide us with a better understanding of the immune signatures of wheezing infants and how they could lead to inflammatory processes in the lung. It also has the potential of discovering novel or diagnostic biomarkers in infants who are susceptible to wheeze.