The main research theme of this division is to study the biology, pathology, immunopathology and pathogenesis of tropical diseases at cellular and molecular levels, with a primary emphasis on the liver fluke, Opisthorchis viverrini , infection and its related cancer–cholangiocarcinoma , the bile duct cancer. Current research in our division includes:
1. Biology of Opisthorchis viverrini : Gaining knowledge of parasite biology is a key step for further investigations on its associated pathology and lead to effective treatment and prevention. We are now characterizing parasite proteins (including lectins) and glycoconjugates using several techniques including proteomic approach. Molecular study of the liver fluke was started as well. cDNA library of O. viverrini (OV) was constructed and OV-EST project is now carrying on. Several interesting genes were cloned and expressed, e.g. cysteine protease.
2. Host-parasite interaction: Host-parasite interaction at the host biliary epithelium is the primary event in opisthorchiasis leading to cholangiocarcinogenesis. The main pathology of infected bile ducts is inflammation, epithelial hyperplasia and periductal fibrosis. We can demonstrate O. viverrini molecules on biliary epithelium. In vitro co-culture study has shown that the liver fluke excretory-secretory molecules can induce biliary cell proliferation. We are now exploring these “oncogenic” molecules in details at molecular level. In addition, global gene expression and protein profiles using cDNA microarray and proteomics, respectively, in Opisthorchis -stimulated biliary cells are currently done in our lab.
3. Immunology and immunopathology of opisthorchiasis: We have previously reported host immune response in O. viverrini infection (Sripa & Kaewkes, 2000b). Opisthorchis antigen can be demonstrated in the biliary epithelium and is associated with intense inflammatory cell infiltration in infected hamster livers (Sripa & Kaewkes, 2000a). This is the breakthrough in induction mechanism of immune response to the infection and immunopathology of opisthorchiasis. Immune response to particular Opisthorchis antigens obtaining from above (1) is in progress. Vaccine development is in the plan.
4. Molecular carcinogenesis: Opisthorchiasis-associated cholangiocarcinoma is a major health problem in Northeast Thailand . We have an animal model, human specimens and “in house” hepatobiliary cell lines established in our lab for molecular carcinogenesis study. Current studies include alterations of oncogenes, tumor suppressor genes, DNA repair genes using several approaches, i.e. conventional PCR, cDNA microarray, proteomics, etc.
5. Tumor & prognostic markers of cholangiocarcinoma: Early detection for primary prevention is the milestone of all cancer. Opisthorchiasis-associated cholangiocarcinoma is a “preventable” cancer by not eating raw fish harboring infective metacercariae of the fluke. Anyway this cannot be applied to older generation who is traditionally addicted. Early detection of the cancer is an alternative though it was an ideal. We are now using proteomic approach to characterize tumor antigens and search for potential tumor markers. Along the line we also explore prognostic markers either cellular or molecular markers.
To accomplish all of these works, we have to collaborate with several investigators both within and outside our institutes. These kind collaborators are detailed in other section. The main man power is from our graduate students and research assistants.
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