Shyue, Song-Kun - IBMS, Sinica

Caveolin-1 (Cav-1) is the major structure protein of caveolae and involved in protein and cholesterol trafficking, signaling transduction and protein degradation. My laboratory has been working on the roles of prostaglandins/eicosanoids in cardiovascular diseases and the role of Cav-1 in bacteria- and LPS-associated immune response and cyclooxygenase (COX)-2 degradation. Previously, we showed that deletion of Cav-1 reduces brain injury in intracerebral hemorrhage (ICH) mouse model. We therefore investigated the role Cav-1 Ab in inflammatory response in ICH.

1. Role of caveolin (Cav-1) antibody (Ab) in immune regulation and therapy for inflammatory diseases. Our results show that Cav-1 Ab treatment alleviated brain damage via reducing brain inflammatory response in intracerebral hemorrhage (ICH) mouse model. Cav-1 Ab treatment reduced microglial activation and modulated microglial M1/M2 polarization toward the M2 phenotype. We are working on the underline mechanism of how Cav-1 Ab modulate monocyte/macrophage polarization and its therapeutic efficacy in inflammatory diseases such as atherosclerosis, other inflammation-related diseases with the monoclonal Cav-1 Abs we developed.

2. Searching for novel genes involved in proteasome- and autophagy-mediated COX-2 degradation. Using CRISPR/Cas9 techniques, we have identified several genes which may mediate COX-2 degradation. Two novel genes are under investigation: one may mediate the retrotranslocation of COX-2 from endoplasmic reticulum (ER) to cytosol, and the other may regulate both ER-associated degradation and autophagy. Several novel genes which may be involved in autophagy have been identified for future study.

3. Novel role of a prostaglandin (PGX) in cardiovascular disease. High dose of non-specific non-steroid anti-inflammatory drugs (NSAIDs) and COX-2 specific inhibitors are associated with increased risk of myocardial infarction (MI), suggesting cardiovascular protective roles of unidentified prostaglandins. We have identified PGX which may play protective roles in cardiovascular diseases. Deletion of PGX increased atherosclerosis in apoE KO mice. Moreover, deletion of PGX increased cardiac fibrosis and deteriorate cardiac function in MI mouse model. Ongoing projects are involved in the function of PGX in lipid homeostasis, endothelial function and cardiac fibrosis.

4. Role of Cav-1 in erythrocytes homeostasis. An ongoing study focus on the molecular mechanism of Cav-1 in red blood cell counts in Cav-1-deleted mice.

5. Adenovirus vector construction and modification. We are in charge for the core facility of recombinant adenovirus vector and have develop an efficient system for adenovirus vector construction and amplification.