Ph.D. Univ. of Massachusetts
We focus on two interrelated research projects: (1) functional characterization of the A2A adenosine receptor (A2AR) and (2) development of novel therapeutic treatment for degenerative diseases including Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD).
A2AR is a major target of caffeine, the most widely used psychoactive substance in the world. My laboratory started from the cloning of this receptor many years ago, and have extend our research interests into the regulation and signal transduction of A2AR under pathophysiological conditions, especially in neurodegenerative diseases. We have also set out to identify and delineate novel pathogeneses (e.g., Galectins-mediated neuroinflammation and abnormal GABAergic signaling) in diseased brains so that better treatments can be designed.
In addition, we developed a group of adenosine analogues targeting simultaneously at A2AR and an adenosine transporter (ENT1). These compounds can enter the brain to enhance the adenosine tone, and can be used to treat mouse models of at least five protein aggregation diseases (including HD, ALS, SCA3, SCA7, AD, and Niemann-Pick type C disease). Results of our findings have led to the application and approvals of patents on applying these compounds to the development of therapeutic treatments for neurodegenerative diseases.
咖啡因是世界上使用最廣泛的精神活化物質，其藥理上的作用目標就是A2AR。我們研究室多年前找到A2AR的基因，近年則研究A2AR在神經退化疾病中的病理功能，調控機轉，和訊號轉導。以神經退化疾病的小鼠模型，我們對於導致神經退化的病理機制也進行深入研究，藉著找到新穎的疾病機轉（例如，神經發炎，異常 GABA 信號），來設計更好的治療方法。
此外，我們開發了一組可同時調控A2AR 和腺苷轉運蛋白1 (ENT1) 的腺苷藥物。這些化合物可以進入大腦來調控腺苷濃度，可治療至少五種蛋白質聚集疾病（包括 HD、ALS、SCA3、SCA7、AD 和 Niemann-Pick C）。這些化合物也已獲得未來應用於神經退化疾病治療方法的專利保護。