Ph.D. Univ. of Massachusetts
My laboratory focuses 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 the past 10 years, we have developed a group of adenosine compounds that have low affinities toward A2AR and an adenosine transporter (ENT1). This class of adenosine compounds can enter the brain to enhance the adenosine tone and produce beneficial effect(s). We and several other laboratories have demonstrated that these compounds can be used to treat mouse models of at least five protein aggregation diseases (including HD, ALS, SCA3, SCA7, and AD). These findings have led to the application and approvals of patents on applying these compounds to the development of therapeutic treatments for neurodegenerative diseases. In addition, we have been actively pursuing the development of biomarkers for neurodegenerative diseases (such as HD), because the lack of reliable biomarkers is a major obstacle for assessing new treatments for brain diseases at this time. We trust that the efforts devoted to the understanding of disease biology and the search for biomarkers would pave the way for the development of new drugs for neurodegenerative diseases.
我們有兩個研究興趣：（1）腺甘A2A受體（adenosine A2A receptor; A2AR）的功能, 及（2）開發能神經退化疾病的新療法。A2AR是咖啡因的主要作用標的。刺激A2AR會活化PKA，PKC和其結合蛋白（TRAX，DISC1，GSK3beta)。我們發現增加腦中的腺甘（adenosine) 可以保護神經細胞的功能。以遺傳小鼠模型及人類腦細胞模型，我們研究神經退化疾病的病理機轉，未來的目標是根據腺甘的藥理特性來開發治療神經退化疾病（包括亨丁頓舞蹈症，漸凍人症，失智症）的藥物。