Introduction Of Researches
本實驗室致力於癌症代謝以及致癌基因的研究，著重以胃癌、口腔癌、攝護腺癌為研究題材，利用蛋白質酵素動力學、細胞生物學、以及生物化學分析方法為基礎，配合蛋白質晶體結構進行癌症致病機制以及抑制劑開發，涉足的領域包括表觀遺傳學、細胞能量代謝、遺傳工程、以及蛋白質結構生物學。
Gastric cancer researches
The PI’s lab has been working in the molecular pathogenesis of Helicobacter pylori that leads to severe gastrointestinal diseases including gastric cancers. We have focused on several virulence factors including VacA, CagA, the blood group antigen-binding adhesion (BabA2) and more recently, cholesterol-α-glucosyltransferase involved in adhesion, invasion, as well as underlying mechanisms in hijacking host-cell signaling. We have also reported antimicrobial resistance in H. pylori isolates in Taiwan, the relationship of IL-1b and IL-10 polymorphisms and H. pylori infection with erosive reflux esophagitis and gastritis and the expression of Foxp3+ Treg that was positively associated with the severity of gastroduodenal diseases.
Figure 3. A proposed model of accumulated cholesteryl glucosides (CGs) in the membranes leads to the raft phase coalescence that triggers the formation of the TFSS pilus. CGs that are synthesized by membrane-bound cholesterol-a-glucosyltransferase (CGT) are associated with the bacterial membranes in the absence of host contact (step 1; ①). Upon attachment with the host membranes (step 2; ②), cholesterol is extracted from the host cells for glucosylation by bacterial CGT. In parallel, the fluctuating CGs in bacteria may drift into the lipid bilayer of the plasma membrane (magnified illustration). Accumulated cholesterol and CGs facilitate the selective lateral-phase segregation and induce the membrane assemblage and raft coalescence on the host-bacterium contact sites, which may serve as a signal to trigger the formation of the TFSS pilus. The mature TFSS subsequently delivers the effectors, CagA and peptidoglycan, into the host cytoplasm (step 3; ③). After translocation, CagA is tyrosine phosphorylated by Src family kinases and triggers downstream signaling events leading to cytoskeletal rearrangement and hummingbird phenotype. The injected peptidoglycan induces the production of pro-inflammatory cytokine interleukin-8 (IL-8). CGs include cholesterol-α-D-glucopyranoside (αCG), cholesteryl-6’-O-tetradecanoyl-α-D-glucopyranoside (αCAG), cholesteryl-6’-O-phosphatidyl-α-D-glucopyranoside (αCGP). Chol, cholesterol; GPL, glycerophospholipid; CGT, cholesterol-α-glucosyltranferase; Csk, C-terminal Src kinase; SHP-2, SH2 domain-containing tyrosine phosphatase-2. Adapted from Wang et al., Mol. Microbiol., 2012.
