Research Topic: Immunobiology of hematopoietic stem cells: Can in vitro differentiated immune cells respond to microbial activators? Rationale and Research Methodology:
Innate immune system plays major role in protecting hosts from various perilous microbes. Since after birth the pluripotent stem cells are forming in specific locations of the body where the hematopoietic progenitor cells are being developed. A small proportion of these cells mature and differentiate into leukocytes :- lymphocytes, monocytes, and polymorphs. Once the cells are ready, they leave the resident areas conceivably ‘naïve’. However, only little is known about the functional achievement of these cells, how (if possible) the immune cells are educated in the environment where they ultimately differentiate. These nondisclosure questions remained ever since, therefore in this project the challenging protocols are to:
Selection and isolation of stem cells from cord blood
Cultivation of hematopoietic stem cells
Induction of leukocytes representing immune system component in vitro
Investigation of cellular responses to mitogens and microbial antigens
Determination of cell phenotypes, and the corresponding effector functions
Research Topic: Leptospirosis and problem related product innovation . Rationale and Research Methodology:
Leptospirosis can affect both human and various different animal species. An increasing trend of climate disaster and environmental changes has influenced the distribution and transmission of this worldwide zoonotic disease, one of the neglected tropical infectious diseases.
Patients suspectious leptospirosis are not easy to differentiate from many other infectious and somewhat non-infectious diseases because of variable clinical manifestations ranged from mild ,non-specific febrile until fatal illness. So.clinical diagnosis is probably often missed,resulting in under-estimate incidence. Most available testing methods are unable to identify the diseased individuals particular at early acute phase of the disease or direct detection of causative microbe itself. Some other approaches have been implemented,such as epidemiological data,field survey,laboratory testing methodsy and/or their combination. Our research and investigation range from pathogenesis through surveillance and control of the disease. A trend in development and innovation designed, programmed and implementing methodological platforms for experimental animal model and patients, as followings
Antibodies based testing assay to enhance detection,identification and characterization of target organisms in animal, human and/or natural environmental samples.
Immunoblotting for identification and study of clinical isolates and laboratory reference leptospires.
Implementation of newly developed immunomagnetic reagents for determining target leptospira in environmental water and host derived specimens.
Nanoparticles and biophysical modified tools for probing or identifying the microorganisms of interest .
Development and application of rapid test kit for early detection of acute leptospirosis in patients and swine.
Research Topic: Developments and vaccines for fascioliasis Rationale and Research Methodology:
Fascioliasis is an animal liver disease caused by trematodes belonging to the genus Fasciola (F. hepatica and F. gigantica). The disease is zoonotic, i.e. a disease of animals that can be transmitted to human. The world Health Organization estimated that at least 2.4 million people are infected, with more than 180 million at risk of infection by the ingestion of aquatic plants that contain the infective metacercariae (WHO, 2002). Susceptible animal reservoir hosts for Fasciola spp. Are domestic animals including cattle, sheep, pigs, buffaloes and goats, as well as wild animals. The disease causes substantial economic loss for meat and dairy industries. The mode of transmission is the fecal-oral route and the major symptoms are weakness. Loss of weight, anemia, fever, hepatomegaly and death in severe infection, especially in young animals. The control strategies are designed to interrupt the parasite life’s cycle. The methods for reducing the prevalence of the disease are composed of the use of anthelmintics, grazing management, biological control, selection and breeding of hosts that are genetically resistant. Triclabendazole is used in infected hosts, but long term use of this drug can cause resistance. There is a need to develop a more cost effective and sustainable method for controlling of this disease, such as vaccines, because they are considered safe to animals and consumers, long-lasting and environment friendly. A number of purified proteins from F. hepatica have been shown to exhibit vaccine potential during trials in cattle, sheep and rats.
4. Aquatic Toxicopathology
Research Topic: Aquactic toxicopathology Rationale and Research Methodology:
Aquatic toxicology is the study of the adverse or toxic effects of chemicals and other anthropogenic materials on aquatic organisms. Toxic effects may include both lethality and sub-lethal effects, such as changes in growth, development, reproduction, pathology, biochemistry, and physiology. The most innocuous chemical substances can have undesirable or distinctly harmful effects when taken up by an organism in sufficient amounts. In contrast, the uptake of minute quantities of toxic chemicals may result in no apparent adverse effects. Therefore, it is an important concept in toxicology that, in general, no chemical is completely safe and no chemical is completely harmful. Little is known about the effect of Thai herb or Thai Traditional Medicine (TTM) on heavy metal exposure on Thailand’s endemic fish species and hence the need to investigate the effect increasing levels of heavy metal contamination will have on fish. In our laboratory, we evaluated the efficiency of those herbs in the term of fish growth rate, hematology, biochemistry, micronuclei and nuclear abnormality studies, atomic absorption analysis, light microscope and scanning electron microscopic study, electrophoresis, etc…The findings of this study can be used as guidelines for developing programs to help the fish, which are cultured near the metal contaminated areas.
5. Genetic Disorders
Research Topic: Characterization of the gene for Shwachman-Diamond syndrome Rationale and Research Methodology:
Shwachman-Diamond syndrome (SDS) is a genetic disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, skeletal abnormalities, and an increased risk of malignant transformation. SDS is one of the most common causes of inherited exocrine pancreatic dysfunction and bone marrow failure. The gene identified was designated SBDS for Shwachman-Bodian-Diamond Syndrome and mutations in this gene account for approximately 90% of all SDS patients. Nonetheless, the biological role of the SBDS protein and the relation of SBDS mutations with the disease outcome have not been fully elucidated. Our research is to utilize baker’s yeast Saccharomyces cerevisiae as a model system to advance the function and the involved pathways of SBDS. This research will assist us in the understanding how SBDS mutations lead to the disease outcome as well as in the development of treatment for SDS patients.
Natural Products and Pathological Changes Prevention
An imbalance between radicals and anti-radicals capacity has been proposed to play an important role in the progression of pathological changes. Oxidative stress is considered a major contributor to various pathologies with serious public health implications such as cardiovascular disease, neurodegenerative disease and cancer. Glutathione is a crucial role in oxidative detoxification. The ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) is involved in metabolic regulation. The GSH/GSSG ratio decreases during normal aging and is further depleted in pathological tissues.
I am interested in the research on Thai natural nutrition to increase the GSH/GSSG ratio conceivably could be used to promote healthy aging and as therapeutics for chronic diseases.
Phytochemicals and antioxidation of Thai natural plants
GSH/GSSG ratio and pathological tissues
Immunohistochemistry in pathological tissues
7. Host-Parasite Interaction: Effects of Parasitic Helminth
Products on host response and carcinogenesis
Rationale and Research Methodology:
Some of parasitic helminth infections are related to human carcinogenesis such as liver fluke, Opisthorchis viverrini, Clonorchis sinensis, inducing bile duct cancer-cholangiocarcinoma; blood fluke, Schistosoma haematobium, causing bladder cancer. Even though epidemiological and animal studies demonstrated these helminth and cancer relationships, molecular mechanisms underlying these phenomena still need to be elucidated. Inflammation is the main host immune response to parasitic infection. Reactive nitrogen/oxygen species released from host effector cells to destroy the invading parasite can also cause the damage to host tissues including DNA damage. Since the worms can survive in host tissue for a long period of time, DNA damage can be accumulated, and if the damage affects the pro-oncogenes or tumor suppressor genes, it likely induces the carcinogenesis. Not only inducing inflammation, parasitic helminthes release large amount of excretory-secretory products into host tissues, some of the molecules are currently identified and characterized. These molecules include proteases, antioxidant enzymes, immunomodulating agents, growth factors, anti-apoptotic factors etc. Given that they are leased into surrounding host tissue and some of which contain tumorigenic activity, these molecules may play role in cancer initiation and progression.
Our research focuses on identification and characterization of excretory-secretory products from Opisthorchis viverrini and Schistosoma haematobium. The putative immunogenic and/or tumorigenic proteins will be selected to be cloned and expressed as recombinant proteins. Functional assays to study biochemical and immunological properties will be performed. The role of these molecules on host-parasite interaction and carcinogenesis will be studied in detail. We aim to identify the new therapeutic targets for treatment and prevention of parasitic infections and cancer induced by these parasitic infections.