Our laboratory has long been working on the role of infectious agents in the pathogenesis of atherosclerosis. We had established rabbit and murine models of bovine herpesvirus-4 (BHV-4) infection-enhanced atherosclerosis. We also collaborate with the Department of Pathobiology, University of Washington, Seattle, U.S.A., and have actively participated in the studies of Chlamydial infection on the pathogenesis of atherosclerosis using murine model. Based on our studies, we hypothesized that impaired immune response in diabetic patients may cause reactivation of persistent pathogens, such as CMV and C. pneumoniae, which subsequently damage the vessel wall and thus to initiate atherosclerosis. Our own study also strongly supports the hypothesis of CMV involvement in the pathogenesis of atherosclerosis in patients with diabetes mellitus. We found that the potential role of different infectious agents in the pathogenesis of atherosclerosis might rely on their biological properties and their infectivity to the hosts with different immunological status. In order to confirmthe hypothesis, BHV-4 infected Apo-/- mice model combination with diabetes mellitus or cyclosporin treatment are under investigation.

Gene polymorphisms are believed to be associated with diseases. Our laboratory is interested in the gene polymorphism and infection susceptibility. The CD14/-260C>Tpolymorphism in the promoter of CD14 gene has been reported to regulate the density of CD14 expression on monocytes.Our previous studies revealed that CD14/-260C>T is very frequent (58%) in Taiwan populations. Furthermore, the single base pair polymorphism of CD14 promoter gene is associated with CD14 expression and Chlamydia-stimulated TNF production, and may thus play some role in the chlamydia-induced inflammatory response.In addition, infection with C. pneumoniae is highly endemic in Taiwan. Recently, we also demonstrated a significant association between the CD14 TT genotype and C. pneumoniae infection. The odds ratio of C pneumoniae infection was 2.08 for CD14 TT genotype. However, the molecular mechanism and signal transduction of CD14 and C. pneumoniae need further investigation.

The Rh blood group is the most polymorphic human blood group system, but with high clinically significance in transfusion medicine. Approximately 30% of apparently Rh-negative Taiwanese were actually RhDel, a rare variant of Rh system, but the D antigen is detectable only by adsorption and elution tests. In our previous study, RhDel was demonstrated to carry a grossly intact RHD gene. The 1227A allele and exon 9 of RHD gene were found in all RhDel donors. We proposed that RHD 1227A can be used as an important and useful genetic marker for RhDel. Further studies are directed to understand the mechanisms of this particular genetic change.

Education

• Ph. D., National Cheng Kung University

Research

• The association between infection and SNPs in the inflammation-associated genes
• Modulated expression and function of toll-like receptor 7 and 8 in hepatitis virus C infection
• Molecular characterization of the missence mutations in A1 domain of human coagulation factor V
• Genotyping of blood groups