報(bào)告題目：Recent advances in Catalomics - Perspective of Drug Discovery in Academia
報(bào)告人：Shao Q. Yao教授
報(bào)告時(shí)間：2019年6月11日（星期二）上午10:00
報(bào)告地點(diǎn)：長安校區(qū)啟翔樓233會(huì)議室
邀請(qǐng)人：李林教授
承辦學(xué)院：柔性電子研究院
聯(lián)系電話：8846-0889
報(bào)告摘要：
Enzymes such as proteases, phosphatases and kinases catalyze virtually every cellular process and metabolic exchange. They not only are instrumental in sustaining life but also are required for its regulation and diversification. Diseases such as cancer can be caused by minor changes in enzyme activities. In addition, the unique enzymes of pathogenic organisms are ripe targets for combating infections. Consequently, nearly one-third of all current drug targets are enzymes. Many enzymes are also engaged in important protein-protein interactions (PPI) by through the so-called reader proteins, resulting in modulating of the enzymatic activities. Little, however, is understood about the physiological roles, substrate specificity, and downstream targets of the vast majority of these important proteins. A key step toward the biological characterization of enzymes as well as their reader proteins, and their adoption as drug targets, is the development of global solutions that bridge the gap in understanding these proteins and their interactions. Catalomics is a field in chemical biology in which chemical and biological tools are developed, enabling large-scale studies of enzymes and their reader proteins at the organism level.1In this presentation, I will discuss key progress made in my laboratory in the last 18 years, in areas related to Catalomics and drug discovery in academia. Specifically, I will focus on the so-called three-Ds (Discovery, Development, and Delivery). I will start with a brief summary of our previous key results in two areas: (1) the use of microarray-based technologies for discovery of potential drug candidates, particularly against normally undruggable targets such as phospho-reader proteins;2and (2) “in situ drug profiling” for cell-based proteome-wide profiling and identification of on- and off-targets of bioactive compounds including FDA-approved drugs and natural products.3Much of my discussion will then focus on detailed accounts on (3) the use of novel methods in protein bioconjugation and material chemical biology to achieve highly efficient, intracellular delivery of therapeutic proteins including antibodies.4I will end the talk by providing a recent example of successful delivery offunctionalenzymes and antibodies to mitochondria, thesubcellularorganelles which serve as not only the powerhouse and energy provider in mammalian cells, but also the shelter for manytherapeuticallyimportant proteins.5
References
1.Uttamchandani, M.; Lu, C.H.S.; Yao, S.Q.,Acc. Chem. Res.,2009,42, 1183.
2.(a) Na, Z.; Peng, B.; Ng, S.; Pan, S.; Lee, J.-S.; Shen, H.M.; Yao, S.Q.,Angew. Chem. Int. Ed.,2015,54, 2515; (b) Peng, B.; Thorsell, A.-G.; Karlberg, T.; Schüler, H.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 248.
3.(a) Pan, S.; Zhang, H.; Wang, C.; Yao, S. C. L.; Yao, S. Q.,Nat. Prod. Rep.,2016,33, 612; (b) Wang, D.; Du, S.; Cazenave-Gassiot, A.; Ge, J.; Lee, J.-S.; Wenk, M.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 5829; (c) Li, Z.; Wang, D.; Li, L.; Pan, S.; Na, Z.; Tan, C.Y.J.; Yao, S.Q.,J. Am. Chem. Soc.,2014,136, 9990; (d) Pan, S.; Jang, S.-Y; Wang, D.; Liew, S. S.; Li, Z.; Lee, J.-S.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 11816; (e) Cheng, K.; Lee, J.-S.; Yao, S.Q.; Ding, K.; Li, Z.,Angew. Chem. Int. Ed.,2017,56, 15044; (f) Pan, S.; Jang, S.-Y.; Liew, S. S.; Fu, J.; Wang, D.; Lee, J.-S.; Shao Q. Yao,Angew. Chem. Int. Ed.,2018,57, 579-583.
4.(a) Yu, C.; Qian, L.; Ge, J.; Fu, J.; Yuan, P.; Yao, S. C. L.; Yao, S. Q.,Angew. Chem. Int. Ed.,2016,55, 9272; (b) Fu, J.; Yu, C.; Li, L.; Yao, S.Q.,J. Am. Chem. Soc.,2015,137, 12153; (c) Yu, C.; Qian, L.; Uttamchandani, M.; Li, L.; Yao, S.Q.,Angew. Chem. Int. Ed.,2015,54,10574; (d) Yuan, P.; Zhang, H.; Qian, L.; Mao, X.; Du, S.; Yu, C.; Peng, B.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 12481; (e) Qian, L.; Fu, J.; Yuan, P.; Du, S.; Huang, W.; Li, L.; Yao, S. Q.,Angew. Chem. Int. Ed.,2018,57, 1532; (f) Du, S.; Liew, S.S.; Li, L.; Yao, S.Q.,J. Am. Chem. Soc.2018,140, 15986; (g) Mao, X.; Yuan, P.; Yu, C.; Li L.;Yao, S.Q.,Angew. Chem. Int. Ed.2018,57, 10257.
5.Yuan, P.; Mao, X.; Wu, X.; Liew, S.S.; Li, L.; Yao, S.Q.,Angew. Chem. Int. Ed.2019,58, 7657.
報(bào)告人簡介：
Shao Q. Yao教授2001年于新加坡國立大學(xué)建立以化學(xué)生物學(xué)為研究方向的課題組，長期致力于酶及相關(guān)生物分子對(duì)生命調(diào)控的研究，以小分子熒光探針、蛋白質(zhì)組學(xué)、微陣列芯片、高通量篩選等為手段，積極推進(jìn)疾病的機(jī)理研究及治療手段的開發(fā)，先后在Nature、Acc.Chem. Res., J. Am. Chem. Soc., Angew. Chem. Int. Ed., Nat. Commun., Proc. Natl. Acad. Sci. U.S.A.等國際著名期刊上發(fā)表高水平學(xué)術(shù)論文200余篇，總引用6800余次，H-index為47。至今已培養(yǎng)博士/碩士研究生30余名，其中有多名學(xué)生和出站博士后在國內(nèi)外知名科研單位從事相關(guān)研究工作；期間也榮獲諸多獎(jiǎng)項(xiàng)，包括Mr & Mrs Sun Chan Memorial Award (2006),Outstanding Scientist Award(2007),ASAIHL-Scopus Young Scientist Award(2008),Asia Rising Stars Lectureship(2013)等,同時(shí)也是Angew. Chem.的International Advisory Board成員之一，并擔(dān)任眾多國際刊物的審稿人。
