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之前小編給大家介紹了2013年諾貝爾生理學(xué)或醫(yī)學(xué)獎(jiǎng)得主Thomas C. Südhof教授重磅加盟CNAF2019的消息，本屆中國核酸國際論壇將由2位諾貝爾獎(jiǎng)得主領(lǐng)銜，前不久還有一位國際學(xué)術(shù)大咖加盟2019CNAF！這位就是美國科學(xué)院院士、美國人文與科學(xué)院院士Dinshaw J. Patel教授。今天，小編就帶大家先來了解一下這位RNAi和表觀遺傳學(xué)領(lǐng)域的重量級(jí)科學(xué)家吧~各位老師同學(xué)如需報(bào)名參會(huì)并同嘉賓大咖面對(duì)面交流，歡迎您聯(lián)系論壇會(huì)務(wù)組。

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美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO
Dinshaw J. Patel教授現(xiàn)為美國科學(xué)院院士，美國人文與科學(xué)院院士，美國紀(jì)念斯隆-凱特琳癌癥中心教授，是RNA干擾和表觀遺傳學(xué)領(lǐng)域的知名結(jié)構(gòu)生物學(xué)專家。Dinshaw J. Patel教授1968年獲得美國紐約大學(xué)化學(xué)博士學(xué)位，1992年成為美國紀(jì)念斯隆-凱特琳癌癥中心教授，并著手建立結(jié)構(gòu)生物學(xué)平臺(tái)。從2000年開始轉(zhuǎn)型用X射線衍射晶體學(xué)技術(shù)，結(jié)合其他生物化學(xué)和生物物理學(xué)手段來探尋生物體內(nèi)有重要調(diào)控功能，并與疾病密切相關(guān)的生物大分子的結(jié)構(gòu)和功能。2004年獲得美國哥倫比亞大學(xué)終身教授職位，在之后的8年里一直從事用核磁共振技術(shù)探索核酸與靶向核酸藥物的結(jié)構(gòu)生物學(xué)研究。2015年11月，Dinshaw J. Patel教授受邀成為南方科技大學(xué)生物系的講座教授。Dinshaw J. Patel教授發(fā)表過500余篇論文和綜述，從其2003年至今的論文摘錄里，每年都有大量的文章發(fā)表在Nature、 Science、 Cell等國際權(quán)威學(xué)術(shù)期刊上。

? ? 主要研究項(xiàng)目? ??

一、RNA沉默
Dinshaw J. Patel教授實(shí)驗(yàn)室的長期研究目標(biāo)包括：（1）通過Dicer的核酸內(nèi)切酶活性將長雙鏈RNA加工成siRNAs；（2）在RNA誘導(dǎo)的沉默復(fù)合物（RISC）中，Argonaute（表現(xiàn)出切割活性的關(guān)鍵組分）可誘導(dǎo)向?qū)ф溄閷?dǎo)的靶RNA裂解。Dinshaw J. Patel教授還對(duì)（3）沿著microRNA (miRNA)生物發(fā)生通路的蛋白-RNA復(fù)合物感興趣，這些復(fù)合物介導(dǎo)初級(jí)miRNAs加工為其前體對(duì)應(yīng)物，以及與miRNA向?qū)ф溄閷?dǎo)的靶RNAs裂解、翻譯抑制或降解相關(guān)的過程。
Dicer介導(dǎo)的dsRNA裂解
1. A phosphate-binding pocket within the platform-PAZ-connector helix cassette of human Dicer.美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO
Tian Y, et al. Molecular cell, 2014, 53(4): 606-616.
2. Dicer Recognizes the 5’-end of RNA for Efficient and Accurate Processing.美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO
Park J E, et al. Nature, 2011, 475(7355): 201.
3.?Inside-Out Mechanism of Dicers from Budding Yeasts.美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO
Weinberg D E, et al. Cell, 2011, 146(2): 262-276.
Argonaute介導(dǎo)的靶RNA裂解
1. Eukaryote-Specific Insertion Elements Control Human ARGONAUTE Slicer Activity.美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO
Nakanishi K, et al. Cell reports, 2013, 3(6): 1893-1900.
2. Nucleation, Propagation and Cleavage of Target RNAs in Eubacterial Ago Silencing Complexes美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO
Wang Y, et al. Nature, 2009, 461(7265): 754.
3. Ternary Eubacterial Argonaute Silencing Complex Containing Guide-Target Duplex Spanning the Seed Segment美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO
Wang Y, et al. Nature, 2008, 456(7224): 921.
piRNA生物發(fā)生
piRNAs是后生動(dòng)物生殖細(xì)胞中各種轉(zhuǎn)座因子轉(zhuǎn)錄和轉(zhuǎn)錄后抑制的指導(dǎo)因子。目前的工作是了解蛋白質(zhì)和相關(guān)RNAs在piRNA生物發(fā)生機(jī)制中的作用。
  1. Cutoff Suppresses RNA Polymerase II termination to ensure expression of piRNA precursors.
  2. Recruitment of Aub and Ago3 to Nuage to form a Krimper assembled ping-pong complex.
  3. Transgenerationally inherited piRNAs trigger piRNA biogeneis.
二、CRISPR-Cas Endonucleses
基于利用CRISPR-Cas系統(tǒng)可編程的dsDNA裂解技術(shù)，可以實(shí)現(xiàn)高效和位點(diǎn)特異性基因組工程。單組分Cas和多組分級(jí)聯(lián)復(fù)合物的結(jié)構(gòu)研究為dsDNA和RNA靶標(biāo)的裂解化學(xué)機(jī)理提供了新的思路。未來的挑戰(zhàn)包括了解不同的CRISPR-Cas系統(tǒng)在努力擴(kuò)展和增強(qiáng)其作為基因組編輯工具的適用性時(shí)所采用的各種機(jī)制。目前還在努力對(duì)涉及進(jìn)化噬菌體抑制蛋白的識(shí)別原理提供結(jié)構(gòu)性的解釋，這些蛋白抑制CRISPR-Cas通路，從而調(diào)節(jié)CRISPR-Cas系統(tǒng)的基因組工程活性。
1. Cpf1 and C2c1 Endoribonucleses.
2. PAM-dependent Target DNA Recognition and Cleavage by C2c1 CRISPR-Cas Endonuclease.

美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO

Yang H, et al. Cell, 2016, 167(7): 1814-1828. e12.
3. Type V CRISPR-Cas Cpf1 endonuclease employs a unique mechanism for crRNA-mediated target DNA recognition.美國科學(xué)院院士Dinshaw J. Patel教授重磅加盟2019中國核酸國際論壇-肽度TIMEDOO
Gao P, et al. Cell research, 2016, 26(8): 901.
除此以外，Dinshaw J. Patel教授實(shí)驗(yàn)室的研究項(xiàng)目還包括：三、組蛋白標(biāo)記介導(dǎo)的表觀遺傳調(diào)控四、DNA甲基化及其與組蛋白甲基化的交互作用

五、組蛋白分子伴侶

六、胞質(zhì)后生動(dòng)物核酸傳感器

七、核糖開關(guān)與核酶

八、蛋白質(zhì)-RNA復(fù)合物介導(dǎo)疾病綜合癥

九、脂質(zhì)轉(zhuǎn)運(yùn)蛋白

榮譽(yù)與獎(jiǎng)項(xiàng)

1961? Jamshetjee N. Tata Fellow1983? AT&T Bell Laboratories Distinguished Technical Staff Award1992? Abby Rockefeller Mauzé Chair in Experimental Therapeutics (MSKCC)

1997? Distinguished Alumnus Award, New York University

1997? Harvey Society (Vice-President 97-98; President 98-99)

2009? Member, National Academy of Sciences, USA

2013? NIH Directors Transformative R01 Award (with Thomas Tuschl and Uwe Ohler)

2014? 2014 FEZANA Jamshed and Shirin Guzdar Excellence in Profession Award

2014? Member, American Academy of Arts and Sciences, USA

學(xué)術(shù)交流活動(dòng)

2010? John D. Roberts Lecture, California Institute of Technology, Pasadena, CA2011? Keystone Symposium on RNA Silencing, Monterey, CA2011? C. C. Tan Lecture, Fudan University, Shanghai, China

2012? IAS Distinguished Lecture, Hong Kong Univ. of Science & Tech., Hong Kong, China

2013? Epigenetics Symposium, University of Michigan, Ann Arbor, MI

2013? NCI Eminent Lecture, Center for Cancer Research, National Cancer Institute, USA

2014? Kiran Mazumdar Shaw Lecture, Inst. Bioinform. & Applied Biotech., Bangalore, India

2014? Dean’s Lecture, Virginia Commonwealth University, Richmond, VA

2014? Master Forum Lecture, Chinese Academy of Medical Sciences, Beijing, China

2014? Cell Press Lab Links Epigenetics Symposium, Beijing, China

2014? IUBMB International Conference, Academica Sinica, Taipei, Taiwan

2014? Shanghai Structural Biology Network Meeting, Shanghai, China

2015? Einstein Professorship of Chinese Academy of Sciences, China

2015? Shizhang Bei Lectureship, CAS Institute Biophysics, Beijing, China

2015? Science Across China Lectureship, Yunnan University, Kunming, China

2015? Joint Life Sciences Center, Tsinghua – Peking Universities, Beijing, China

2016? Distinguished Lecture, KAUST, Saudi Arabia

2016? RNA: Structure Meets Function Meeting, Stockholm, Sweden

2016? Shenzhen International Biotechnology Summit, Shenzhen, China

主要代表文章

[1] Stromme, C. B., Hammond, C., Huang, H., Patel, D. J. & Groth, A. (2017). Histone chaperone networks shaping chromatin function. Nat. Rev. Mol. Cell. Biol. 18, 141-158.[2] Guo, T. W., Bartesaghi, A., Yang, H., Falconieri, V., Rao, P., Merk, A., Eng, E. T., Raczkowski, A. M., Fox, T., Earl, L. A., Patel, D. J. & Subramaniam, S. (2017). Cryo-EM structures reveal mechanism and inhibition of DNA targeting by a CRISPR-Cas surveillance complex. Cell, 171, 414-426.[3] Yang, H., Gao, P., Rajashankar, K. R., & Patel, D. J. (2017). PAM-dependent target DNA recognition and cleavage by C2c1 CRISPR-Cas endonuclease. Cell, 167,1814-1828.

[4] Saredi, G., Huang, H., Hammond, C., Bekker-Jensen, S., Forne, I., Reveron-Gomez, N., Foster, B. M., Mlejnkova, L., Bartke, T., Cejka, P., Mailand, N., Imhof, A., Patel, D. J. and Groth, A. (2016). H4 K20me0 marks post-replicative chromatin and recruits the TONSL-MMS22L DNA repair complex. Nature, 534, 714-718.

[5] Sun, X-J., Wang, Z., Wang, L., Jiang, Y., Chen, W-Y., Melnick, A., Patel, D. J., Nimer, S. D. & Roeder, R. G. (2013). A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis. Nature, 500, 93-97.

[6] Simanshu, D. K., Kamlekar, R. K., Wijesinghe, D. S., Zou, X., Zhai, X., Mishra, S. K., Molotkovsky, J. G., Malinina, L., Hincliffe, E. H., Chalfant, C. E., Brown, R. E. & Patel, D. J. (2013). Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids. Nature, 500, 463-467.

[7] Gao, P., Ascano, M., Wu, Y., Barchet, W., Gaffney, B. L., Zillinger, T., Serganov, A., Jones, R. A., Hartmann, G., Tuschl, T. and Patel, D. J. (2013). Cyclic [G(2’,5’)pA(3’,5’)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase. Cell, 153, 1094-1107.

[8] Johnson, L. M., Du, J., Hale, C. J., Bischof, S., Feng, S., Chodavarapu, R. K., Zhong, X., Marson, G., Pellergrini, M., Segal, D. J., Patel, D. J. and Jacobsen, S. E. (2014). SRA/SET domain proteins link RNA polymerase V occupancy to DNA methylation. Nature, 507, 124-128.

[9] Zhong, X., Du, J., Hale, C. J., Gallego-Bartolome, J., Feng, S., Vashisht, A. A., Chory, J., Wohlschlegel, J. A., Patel, D. J. and Jacobsen, S. E. (2014). Molecular mechanism of action of plant DRM de novo DNA methyltransferases. Cell. 157, 1050-1060.

[10] Du, J., Johnson, L. M., Jacobsen, S. E. and Patel, D. J. (2015). DNA methylation pathways and their crosstalk with histone methylation. Nat. Rev. Mol. Cell Biol. 16, 519-532.