Ph.D. University of Kentucky
My group is interested in investigating the functional role of heme oxygenase-1 (HO-1), which is an ER-anchored enzyme catalyzing the oxidative degradation of cellular heme to free iron, carbon monoxide (CO), and biliverdin, in inflammation-associated diseases, including cardiovascular diseases and cancer. Compelling evidence has demonstrated that HO-1 exerts potent anti-inflammatory and antioxidant effects via the action of CO and biliverdin, respectively. Although HO-1 provides multiprotective functions in cardiovascular system, HO-1 promotes tumorigenesis in cancer. We recently identified the tumor suppressor TRC8 is an E3 ligase mediating the ubiquitination and degradation of HO-1. We also found that HO-1 is susceptible to the intramembrane cleavage by an ER-resident peptidase and translocates into nucleus to promote cancer cell proliferation and invasion independent of its enzymatic activity. Studies are currently ongoing to investigate the mechanism underlying the tumorigenic function of nuclear HO-1. Moreover, the role of myeloid HO-1 implicated in cancer-associated inflammation and its impacts on cancer metastasis is also under investigation.
本實驗室的研究主要為探討第一型血紅素氧化脢 (HO-1)在發炎相關之心血管疾病和癌症中之角色 . 許多的研究証實HO-1可藉由其分解細胞內血紅素所釋放出來的具有抗發炎和抗氧化之產物, 一氧化碳和膽紅素, 而保謢細胞. 雖然HO-1可藉由多重途徑達到保謢心血管之作用, 但HO-1卻可促進癌細胞的生長和轉移. 我們最近的研究發現抑癌基因蛋白TRC8可藉由促進HO-1的泛素化和分解而達到抑制癌細胞生長之作用 . 此外我們亦發現HO-1 可經由蛋白裂解脢之作用，而離開內質網，進入細胞核而促進癌細胞的生長卻不須要依賴其酵素活性. 目前我們將進一步探討其可能的分子机制. 並對白血球中HO-1 之表現是否影響和癌症相關之發炎反應並癌細胞的轉移作深入探討 .