个人简介

Medical School, 1989-1991; Post-doctoral fellow, University of Colorado, 1991-1994; Assistant/Associate professor, (1994-1998), Professor, (1999-2001), Yale University. Professor of Biochemistry & Molecular Biology, UC Berkeley, (2002-). Howard Hughes Medical Investigator 1997 to present. Packard Foundation Fellow Award, 1996; NSF Alan T. Waterman Award, 2000. Member, National Academy of Sciences, 2002. Member, American Academy of Arts and Sciences, 2003; American Association for the Advancement of Science Fellow Award, 2008; Member, Institute of Medicine of the National Academies, 2010.

研究领域

Chemical Biology Ribozymes and RNA Machines: RNA forms a variety of complex globular structures, some of which function like enzymes or form functional complexes with proteins. There are three major areas of focus in the lab: catalytic RNA, the function of RNA in the signal recognition particle and the mechanism of RNA-mediated internal initiation of protein synthesis. We are interested in understanding and comparing catalytic strategies used by RNA to those of protein enzymes, focusing on self-splicing introns and the self-cleaving RNA from hepatitis delta virus (HDV), a human pathogen. We are also investigating RNA-mediated initiation of protein synthesis, focusing on the internal ribosome entry site (IRES) RNA from Hepatitis C virus. Cryo-EM, x-ray crystallography and biochemical experiments are focused on understanding the structure and mechanism of the IRES and its amazing ability to hijack the mammalian ribosome and associated translation factors. A third area of focus in the lab is the signal recognition particle, which contains a highly conserved RNA required for targeting proteins for export out of cells. Each of these projects seeks to understand the molecular basis for RNA function, using a combination of structural, biophysical and biochemical approaches.

Chemical Biology Ribozymes and RNA Machines: RNA forms a variety of complex globular structures, some of which function like enzymes or form functional complexes with proteins. There are three major areas of focus in the lab: catalytic RNA, the function of RNA in the signal recognition particle and the mechanism of RNA-mediated internal initiation of protein synthesis. We are interested in understanding and comparing catalytic strategies used by RNA to those of protein enzymes, focusing on self-splicing introns and the self-cleaving RNA from hepatitis delta virus (HDV), a human pathogen. We are also investigating RNA-mediated initiation of protein synthesis, focusing on the internal ribosome entry site (IRES) RNA from Hepatitis C virus. Cryo-EM, x-ray crystallography and biochemical experiments are focused on understanding the structure and mechanism of the IRES and its amazing ability to hijack the mammalian ribosome and associated translation factors. A third area of focus in the lab is the signal recognition particle, which contains a highly conserved RNA required for targeting proteins for export out of cells. Each of these projects seeks to understand the molecular basis for RNA function, using a combination of structural, biophysical and biochemical approaches

近期论文

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RNA Targeting by Functionally Orthogonal Type VI-A CRISPR-Cas Enzymes. East-Seletsky A, O'Connell MR, Burstein D, Knott GJ, Doudna JA. NMol Cell. 2017 May 4;66(3):373-383.e3. doi: 10.1016/j.molcel.2017.04.008. CRISPR-Cas9 Structures and Mechanisms. Jiang F, Doudna JA. Annu Rev Biophys. 2017 Mar 30. doi: 10.1146/annurev-biophys-062215-010822. [Epub ahead of print] Targeted gene knock-in by homology-directed genome editing using Cas9 ribonucleoprotein and AAV donor delivery. Gaj T, Staahl BT, Rodrigues GM, Limsirichai P, Ekman FK, Doudna JA, Schaffer DV. Nucleic Acids Res. 2017 Mar 2. doi: 10.1093/nar/gkx154. [Epub ahead of print] Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain. Lintner NG, McClure KF, Petersen D, Londregan AT, Piotrowski DW, Wei L, Xiao J, Bolt M, Loria PM, Maguire B, Geoghegan KF, Huang A, Rolph T, Liras S, Doudna JA, Dullea RG, Cate JH. PLoS Biol. 2017 Mar 21;15(3):e2001882. doi: 10.1371/journal.pbio.2001882. eCollection 2017. RNA-based recognition and targeting: sowing the seeds of specificity. Gorski SA, Vogel J, Doudna JA. Nat Rev Mol Cell Biol. 2017 Feb 15. doi: 10.1038/nrm.2016.174. [Epub ahead of print] Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes. Staahl BT, Benekareddy M, Coulon-Bainier C, Banfal AA, Floor SN, Sabo JK, Urnes C, Munares GA, Ghosh A Doudna JA. Nat Biotechnol. 2017 Feb 13. doi: 10.1038/nbt.3806. [Epub ahead of print] RNA and DNA Targeting by a Reconstituted Thermus thermophiles Type III-A CRISPR-Cas System. Liu TY, Iavarone AT, Doudna JA1. PLoS One. 2017 Jan 23;12(1):e0170552. doi: 10.1371/journal.pone.0170552. eCollection 2017. Mutations in Cas9 Enhance the Rate of Acquisition of Viral Spacer Sequences during the CRISPR-Cas Immune Response. Heler R, Wright AV, Vucelja M, Bikard D, Doudna JA, Marraffini LA. Mol Cell. 2017 Jan 5;65(1):168-175. doi: 10.1016/j.molcel.2016.11.031. Epub 2016 Dec 22. Cornerstones of CRISPR-Cas in drug discovery and therapy.Fellmann C, Gowen BG, Lin PC, Doudna JA, Corn JE. Nat Rev Drug Discov. 2016 Dec 23. doi: 10.1038/nrd.2016.238. [Epub ahead of print] New CRISPR-Cas systems from uncultivated microbes. SBurstein D, Harrington LB, Strutt SC, Probst AJ, Anantharaman K, Thomas BC, Doudna JA, Banfield JF. Nature. 2016 Dec 22. doi: 10.1038/nature21059. [Epub ahead of print] RNA scanning of a molecular machine with a built-in ruler. Koh HR, Kidwell MA, Doudna JA, Myong S. J Am Chem Soc. 2016 Dec 13. [Epub ahead of print] ATAC-see reveals the accessible genome by transposase-mediated imaging and sequencing. Chen X, Shen Y, Draper W, Buenrostro JD, Litzenburger U, Cho SW, Satpathy AT, Carter AC, Ghosh RP, East-Seletsky A, Doudna JA, Greenleaf WJ, Liphardt JT, Chang HY. Nat Methods. 2016 Oct 17. doi: 10.1038/nmeth.4031. [Epub ahead of print] A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells. Hultquist JF, Schumann K, Woo JM, Manganaro L, McGregor MJ, Doudna J, Simon V, Krogan NJ, Marson A. Cell Rep. 2016 Oct 25;17(5):1438-1452. doi: 10.1016/j.celrep.2016.09.080. Insights into HIV-1 proviral transcription from the structure and dynamics of the Tat:AFF4:P-TEFb:TAR complex. Schulze-Gahmen U, Echeverria I, Stjepanovic G, Bai Y, Lu H, Schneidman-Duhovny D, Doudna JA, Zhou Q, Sali A, Hurley JH. Elife.2016 Oct 12;5. pii: e15910. doi: 10.7554/eLife.15910. [Epub ahead of print] Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection. East-Seletsky A, O'Connell MR, Knight SC, Burstein D, Cate JH, Tjian R, Doudna JA. Nature. 2016 Sep 26. doi: 10.1038/nature19802. [Epub ahead of print] Real-time observation of DNA recognition and rejection by the RNA-guided endonuclease Cas9. Singh D, Sternberg SH, Fei J, Doudna JA, Ha T. Nat Commun. 2016 Sep 14;7:12778. doi: 10.1038/ncomms12778. Applications of CRISPR technologies in research and beyond. Barrangou R, Doudna JA. Nat Biotechnol. 2016 Sep 8:933-941. doi: 10.1038/nbt.3659. [Epub ahead of print] Protecting genome integrity during CRISPR immune adaptation. Wright AV, Doudna JA. Nat Struct Mol Biol.2016 Sep 5. doi: 10.1038/nsmb.3289. [Epub ahead of print] DNA Targeting by a Minimal CRISPR RNA-Guided Cascade. Hochstrasser ML, Taylor DW, Kornfeld JE, Nogales E, Doudna JA. Mol Cell. 2016 Sep 1;63(5):840-51. doi: 10.1016/j.molcel.2016.07.027. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Lee AS, Kranzusch PJ, Doudna JA, Cate JH. Nature. 2016 Jul 27. doi: 10.1038/nature18954. [Epub ahead of print] Reconstitution of selective HIV-1 RNA packaging in vitro by membrane-bound Gag assemblies. Carlson LA, Bai Y, Keane SC, Doudna JA, Hurley JH. Elife 2016 Jun 25;pii: e14663. doi: 10.7554/eLife.14663. [Epub ahead of print] CRISPR Immunological Memory Requires a Host Factor for Specificity. Nuñez JK, Bai L, Harrington LB, Hinder TL, Doudna JA. Mol Cell 2016 Jun 16;62(6):824-33. Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch. Oakes BL, Nadler DC, Flamholz A, Fellmann C, Staahl BT, Doudna JA Savage DF. Nat Biotechnol. 2016 Jun;34(6):646-51. Nucleosome breathing and remodeling constrain CRISPR-Cas9 function. Isaac RS, Jiang F, Doudna JA, Lim WA, Narlikar GJ, Almeida RA Elife 2016 Apr 28;5. pii: e13450. Programmable RNA Tracking in Live Cells with CRISPR/Cas9. Nelles DA, Fang MY, O'Connell MR, Xu JL, Markmiller SJ, Doudna JA, Yeo GW Cell 2016 Apr 7;165(2):488-96.