西湖名师论坛第二十五期 Westlake Master Forum Yi-Ping Li

Cathepsin K and Gα13 as the novel therapeutic targets for inflammatory diseases

来源:WIAS 发布时间:2018-12-27 作者: 阅读数:1023次


时间:2018年12月27日(周四)   上午10:00 – 11:00

Time: December 27, 2018,  10:00-11:00AM

地点:西湖大学云栖校区5号楼301会议室

Venue: Meeting Room301, 3rd Floor, Building 5, Yunqi Campus

主持人: 郑厚峰博士

Host: Dr. Houfeng Zheng

 

主讲嘉宾/Speaker:

Prof. Yi-Ping Li

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Jay McDonald Endowed Professor, Department of Pathology, The University of Alabama at Birmingham (UAB)


李亦平教授毕业于浙江大学化学系,获中国科学院生物化学研究所博士学位,美国哈佛大学Forsyth研究所博士后,原哈佛大学医学院附属Forsyth研究所终身研究员(终身教授)。现任美国阿拉巴马大学伯明翰分校(UAB) Jay McDonald 冠名教授,阿拉巴马大学骨代谢性骨病研究中心资深副主任,哈佛大学医学院附属Forsyth研究所兼职教授, UAB口腔医学院兼职教授, UAB口腔面颔疾病研究中心共同主任, 浙江大学求是讲座教授。以第一或通讯作者在Nature Genetics, Genes and Development, The Proceedings of the National Academy of Sciences of the United States of America (PNAS), Nucleic Acids Research等杂志发表论文70多篇。

 

讲座摘要/Abstract :

Although many efforts have been made to develop therapies for Periodontitis (PD) and rheumatoid arthritis (RA), none of these therapies are highly effective. There is a compelling need to explore novel therapeutic targets to develop safer and more effective therapies for PD and RA. We believe that the current lack of highly effective therapies is largely due to incomplete knowledge of the mechanism of PD and RA pathogenesis. We are studying the mechanisms underlying how Cathepsin K and Gα13 characterized from osteoclasts regulate inflammatory diseases such as PD and RA, which can provide novel therapeutic targets for diseases related to inflammation and bone destruction. Although TLRs are critical for host defense and inflammatory diseases, the role of TLRs in the pathogenesis of periodontitis remains largely unknown. Our discovery of the critical role of Cathepsin K (Ctsk) and Gα13 in osteoclast function provides a strong rationale for this protease and signaling regulator as a target to prevent bone loss. Recently, we found that adeno-associated virus (AAV) Ctsk shRNAi (AAV-shRNA-Ctsk) mediated silencing and prevents both bone loss and inflammation in a mouse model of endodontic disease. Moreover, we reported that Ctsk is required for TLR9 signaling in a mouse model of rheumatoid arthritis. Notably our preliminary data showed that Cathepsin K gene knockout and Ctsk silencing -mediated by AAV-shRNA-Ctsk dramatically prevents both bone loss and inflammation in a mouse model of periodontitis. Surprisingly we noted that AAV mediated overexpression of local Gα13 constitutively active form (Gα13CA) not only intensely reduced bone destruction, but also dramatically inhibited inflammation in RA, indicating that Gα13CA could protect against inflammation in a mouse model of RA. These studies strongly indicate that Ctsk and Gα13 are a major “osteoimmune gene” that can be targeted to control both inflammation and bone loss. Collectively, these studies suggest that Ctsk and Gα13 may be a key regulator of TLR signaling and that targeting Ctsk and Gα13 to attenuate TLR signaling may be an effective therapy Periodontitis (PD) and rheumatoid arthritis (RA).

 

联系人:科技合作部 沈老师shenxiaolian@westlake.edu.cn