齊磊 - 台湾清华大学

个人简介

We believe technologies and bioengineering will transform future medicine, which bring positive changes to understanding and curing diseases. We are interested in developing technologies for discovery-based synthetic biology and gene and cell therapy. We are eager to learning more about the functions of the mammalian genome and how to read and manipulate the genome for disease treatment. For discovery-based synthetic biology, we use principles of synthetic biology to engineer molecules and genetic circuits to learn new biology. We use human T cells or stem cells as our engineering chassis, and design them to detect new antigens to better kill cancer cells or integrate many environmental and genomics cues to maintain or change cell fates for body repairing. We are interested in learning how genetics circuits can integrate with the host genomic programs to more powerful sensor-processor-actuator systems. By engineering at the scale from molecular to cellular to organismal level, we hope to make synthetic biology a better discovery tool. For gene and cell therapy, we develop new tools for treatment of cancer, genetic disease, or infectious disease. We developed the first use of the nuclease deactivated dCas9 for gene regulation and epigenome editing. We developed CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) for targeted gene activation and repression. We developed LiveFISH for live imaging of DNA and RNA in living cells. We developed CRISPR-GO that allows manipulation of the 3D spatial organization of the genome. We developed and test PAC-MAN as a possible treatment to fight influenza, SARS-CoV-2 and RNA viruses. I hope some of these tools will change future gene and cell therapy. We combine CRISPR genome engineering, molecular engineering, synthetic biology, and bioinformatics to study human genomics, as well as to develop novel gene and cell therapy to treat cancer, degeneration, and infectious diseases.

研究领域

Bioengineering and of Chemical and Systems Biology

近期论文

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59. Abbott TR#, Dhamdhere G#, Liu Y#, Lin X#, Goudy L#, Zeng L, Chemparathy A, Chmura S, Heaton NS, Debs R, Pande T, Endy D, La Russa MF*, Lewis DB*, Qi LS*. Development of CRISPR as an antiviral strategy to combat SARS-CoV-2 and influenza. Cell. 181(4): 865-876. 2020 May 14. (#equal contribution). Read Wired, Berkeley Lab, Fierce Biotech. 58. Sarkar TJ, Quarta M, Mukherjee S, Colville A, Paine P, Doan L, Tran CM, Chu CR, Horvath S, Qi LS, Bhutani N, Rando TA, Sebastiano V. Transient non-integrative expression of nuclear reprogramming factor promotes multifaceted amelioration of aging in human cells. Nat Commun. 11(1): 1545. 2020 Mar 24. 57. Wang M, Zhang G, Zhang T, Cui X, Wang S, Gao S, Wang Y, Liu Y, Bae JH, Y WH, Qi LS, W L, Liu R. Fibrinogen alpha chain knockout promotes tumor growth and metastasis through integrin-AKT signaling pathway in lung cancer. Mol Cancer Res. 2020 Mar 23. 56. Bodapati S#, Daley TP#, Lin X, Zou J, Qi LS*. A benchmark of algorithms for the analysis of pooled CRISPR screens. Genome Biol. 21:62. 2020 Mar 9. (#Equal contribution) (Review) 55. Nishiga M, Qi LS, Wu JC. Therapeutic genome editing in cardiovascular diseases. Adv Drug Deliv Rev. 2020 Feb 21. (Review) 54. Kempton HR, Goudy LE, Love KS, Qi LS*. Multiple Input Sensing and Signal Integration Using a Split Cas12a System. Mol. Cell 78(1): 184-191. 2020 Feb 5. 53. Lee JY, Dominguez AA, Nam S, Stowers RS, Qi LS, Chaudhuri O. Identification of cell context-dependent YAP-associated proteins reveals β1 and β4 integrin mediate YAP translocation independently of cell spreading. Sci. Rep. 9(1): 17188. 2019 Nov 20. 52. Wang H, Nakamura M, Abbott TR, Zhao D, Luo K, Yu C, Nguyen CM, Lo A, Daley TP, La Russa M, Liu Y, Qi LS*. CRISPR-mediated live imaging of genome editing and transcription. Science 365(6459): 1301-1305. 2019 Sep 20. Read Spectrum, Stanford news. 51. Chavez M, Qi LS*. Site-programmable transposition: shifting the paradigm for CRISPR-Cas systems. Mol. Cell 75(2): 206-208. 2019 Jul 25 (Perspective). 50. Shariati SA, Dominguez AA, Xie S, Wernig M, Qi LS, Skotheim JM. Reversible Disruption of Specific Transcription Factor-DNA Interactions Using CRISPR/Cas9. Mol. Cell 74(3):622-633.e4. 2019 May 2. 49. Lee JY, Chang JK, Dominguez AA, Chang HLJ, Varma S, Qi LS, West RB, Chaudhuri O. YAP-independent mechanotransduction drives breast cancer progression. Nat. Commun. 10(1):1848. 2019 Apr 23. 48. Kempton HR, Qi LS*. When genome editing goes off-target. Science 364(6437): 234-236. 2019 Apr 19 (Perspective). 47. Shortt K, Heruth DP, Zhang N, Wu W, Singh S, Li DY, Zhang LQ, Wyckoff GJ, Qi LS, Friesen CA, Ye SQ. Identification of Novel Regulatory Genes in APAP Induced Hepatocyte Toxicity by a Genome-Wide CRISPR-Cas9 Screen. Sci. Rep. 9(1): 1396. 2019 Feb 4. 46. Nakamura M, Srinivasan P, Chavez M, Carter MA, Dominguez AA, La Russa M, Lau MB, Abbott TR, Xu X, Zhao D, Gao Y, Kipniss NH, Smolke CD, Bondy-Denomy J, Qi LS*. Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells. Nat. Commun. 10:194. 2019 Jan 14. 45. Wang H, Xu X, Nguyen CM, Liu Y, Gao Y, Lin X, Daley TP, Kipniss NH, La Russa M, Qi LS*. CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization. Cell 175(5): 1405–1417. 2018 Nov 15. Read Science, Nature, Quanta Magazine, Stanford News. 44. Abbott TR, Qi LS*. Evolution at the Cutting Edge: CRISPR-Mediated Directed Evolution. Mol Cell 72(3): 402-403. 2018 Nov 1 (Perspective). 43. Liu Y#, Yu C#, Daley TP#, Wang F, Cao WS, Bhate S, Lin X, Still C, Liu H, Zhao D, Wang H, Xie XS, Ding S, Wong WH, Wernig M, Qi LS*. CRISPR Activation Screens Systematically Identify Factors that Drive Neuronal Fate and Reprogramming. Cell Stem Cell 23(5): 758-771. 2018 Oct 11. (#Equal contribution) Selected in Cell Stem Cell Best of 2018. 42. Daley TP, Lin Z, Lin X, Liu Y, Wong WH, Qi LS. CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens. Genome Biol. 19:159. 2018 Oct 8. 41. Gu T, Lin X, Cullen SM, Luo M, Jeong M, Estecio M, Shen J, Hardikar S, Sun D, Su J, Rux D, Guzman A, Lee M, Qi LS, Chen J, Kyba M, Huang Y, Chen T, Li W, Goodell MA. DNMT3A and TET1 cooperate to regulate promoter epigenetic landscapes in mouse embryonic stem cells. Genome Biol. 19:88. 2018 July 12. 40. Xu X, Qi LS*. A CRISPR-dCas Toolbox for Genetic Engineering and Synthetic Biology. J Mol. Biol. pii: S0022-2836(18)30666-1. 2018 Jun 26. (Review) 39. Wang B, Zhou J, Banie L, Reed-Maldonado AB, Ning H, Lu Z, Ruan Y, Zhou T, Wang HS, Oh BS, Wang G, Qi LS, Lin G, Lue TF. Low‐intensity extracorporeal shock wave therapy promotes myogenesis through PERK/ATF4 pathway. Neurourol. Urodyn. 37(2):699-707. 2018 Feb. 38. Liu P, Chen M, Liu Y, Qi LS, Ding S. CRISPR-based chromatin remodeling of the endogenous Oct4 or Sox2 locus enables reprogramming to pluripotency. Cell Stem Cell 22: 252-261. 2018 Feb 1. 37. Kipniss NK#, Dingal PCDP#, Abbott TR, Gao Y, Wang H, Dominguez AA, Labanieh L, Qi LS*. Engineering cell sensing and responses using a GPCR-coupled CRISPR-Cas system. Nat. Commun. 8(1):2212. 2017 Dec 20. (#Equal contribution) 36. Lo A, Qi LS*. Genetic and epigenetic control of gene expression by CRISPR–Cas systems. F1000Res 6: 747. 2017 May 25. (Review) 35. Zhou XX, Zou X, Chung HK, Gao Y, Liu Y, Qi LS, Lin MZ. A Single-Chain Photoswitchable CRISPR-Cas9 Architecture for Light-Inducible Gene Editing and Transcription. ACS Chem. Biol. 13(2):443-448. 2017 Sep 22. 34. Chen M, Qi LS. Repurposing CRISPR System for Transcriptional Activation. Adv. Exp. Med. Biol. 983:147-157. 2017 Jun 22. (Review) 33. Du D#, Roguez A#, Gordon DE, Chen M, Chen SH, Shales M, Shen JP, Ideker T, Mali P, Qi LS*, Krogan NJ*. Genetic interaction mapping in mammalian cells using CRISPR interference. Nat Methods. 14(6): 577-580. 2017 May 8. (#Equal contribution) 32. Shen JP, Zhao D, Sasik R, Luebeck K, Birmingham A, Bojorquez-Gomez A, Licon K, Klepper K, Pekin D, Beckett AN, Sanchez KS, Thomas A, Kuo CC, Du D, Roguez A, Lewis NE, Chang AN, Kreisberg JF, Krogan NJ, Qi LS, Ideker T, Mali P. Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions. Nat Methods. 14(6): 573-576. 2017 Mar 20. 31. Takei Y, Shah S, Harvey S, Qi LS, Cai L. Multiplexed dynamic imaging of genomic loci in single cells by combined CRISPR imaging and DNA sequential FISH. Biophys J. 112: 1173-1176. 2017 Apr 17. 30. Gao Y#, Xiong X#, Wong S, Charles EJ, Lim WA, Qi LS*. Complex Transcriptional Modulation with Orthogonal and Inducible dCas9 Regulators. Nat. Methods. 13(12):1043-1049. 2016 Dec. (#Equal contribution) 29. Xiong X, Chen M, Lim WA, Zhao D, Qi LS*. Genome engineering and disease research. Annu. Rev. Genomics Hum. Genet. 17:131-154. 2016 Aug 31. (Review) 28. Peters JM, Colavin A, Shi H, Czarny ML, Larson MH, Wong S, Hawkins JS, Lu CHS, Koo BM, Marta E, Shiver AL, Whitehead EH, Weissman JS, Brown ED, Qi LS*, Huang KC*, Gross CA*. A comprehensive, CRISPR-based functional analysis of essential genes in bacteria. Cell 165: 1493-1506. 2016 Jun 2. 27. Wang H, La Russa M, Qi LS*. CRISPR-Cas9 in genome editing and beyond. Annu. Rev. Biochem. 85: 227-264. 2016 Jun 2. (Review) The Top 10 cited article in the Annual Review Journals in 2016. 26. Mandegar MA, Huebsch N, Frolov EB, Shin E, Truong A, Chan AH, Olvera MP, Chan AH, Miyaoka Y, Holmes K, Spencer CI, Judge LM, Gordon DE, Eskildsen TV, Villalta JE, Horlbeck MA, Gilbert LA, Krogan NJ, Sheikh SP, Weissman JS, Qi LS, So PL, Conklin BR. CRISPR interference efficiently induces specific and reversible gene silencing in human iPSCs. Cell Stem Cell. 18: 541–553. 2016 Apr 7. 25. Qin H, Hejna M, Liu Y, Percharde M, Wossidlo M, Blouin L, Durruthy-Durruthy J, Wong P, Qi Z, Yu J, Qi LS, Sebastiano V, Song JS, Ramalho-Santos M. YAP Induces Human Naïve Pluripotency. Cell Reports. 14: 2301–2312. 2016 Mar 15. 24. Dominguze AA, Lim WA*, Qi LS*. Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation. Nat. Rev. Mol. Cell. Biol. 17: 5-15. 2016 Jan. (Review) 23. Du D, Qi LS*. An Introduction to CRISPR Technology for Genome Activation and Repression in Mammalian Cells. Cold Spring Harb Protoc 2016: pdb.top086835. 2016 Jan 4. (Protocol) 22. La Russa MF, Qi LS*. The new state of the art: Cas9 for gene activation and repression. Mol. Cell Biol. 35: 3800-3809. 2015 Nov 15. (Review) 21. Liu H, Wei Z, Dominguez AA, Li Y, Wang X*, Qi LS*. CRISPR-ERA: a comprehensive design tool for CRISPR-mediated gene editing, repression and activation. Bioinformatics 31: 3676-3678. 2015 Nov 15. 20. Peters JM, Silvis MR, Zhao D, Hawkins JS, Gross CA*, Qi LS*. Bacterial CRISPR: accomplishments and prospects. Curr. Opin. Microbiol. 27: 121–126. 2015 Sep 9. (Review) 19. Sokolik, Liu Y, Bauer D, McPherson J, Broeker M, Heimberg G, Qi LS, Sivak DA, Thomson M. Transcription factor competition allows embryonic stem cells to distinguish authentic signals from noise. Cell Syst. 1(2): 117-129. 2015 Aug 26. 18. Hawkins JS, Wong S, Peters JM, Almeida R, Qi LS*. Targeted transcriptional repression in bacteria using CRISPR interference (CRISPRi). Methods Mol. Biol. 1311: 349-362. 2015 May. (Protocol) 17. Yu C#, Liu Y#, Ma T, Xu S, Liu K, Zhang Y, La Russa MF, Xie M, Ding S*, Qi LS*. Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell 16: 142-147. 2015 Feb 5. (#Equal contribution) 16. Zalatan JG, Lee ME, Gilbert LA, Almeida R, Tsai JC, Whitehead EH, La Russa MF, Weissman JS, Dueber JE, Qi LS*, Lim WA*. Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell 160: 339-350. 2015 Jan 15. (Cover article) 15. Ji W, Lee D, Wong E, Dadlani P, Dinh D, Huang V, Kearns K, Teng S, Chen S, Haliburton J, Heimberg G, Heineike B, Ramasubramanian A, Stevens T, Helmke KJ, Zepeda V, Qi LS, Lim WA. Specific gene repression by CRISPRi system transferred through bacterial conjugation. ACS Synth. Biol. 3(12): 929-931. 2014 Dec 19. 14. Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS, Vale RD. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 159(3): 635-646. 2014 Oct 23. 13. Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC, Qi LS, Kampmann M, Weissman JS. Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159(3): 647-661. 2014 Oct 23. 12. Qi LS*, Arkin AP*. A versatile platform for microbial engineering using synthetic noncoding RNAs. Nat. Rev. Microbiol. 12: 341-354. 2014 May. (Review) 11. Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, Li GW, Park J, Blackburn EH, Weissman JS, Qi LS*, Huang B*. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155: 1479-1491. 2013 Dec 19. 10. Larson MH, Gilbert LA, Wang X, Lim WA, Weissman JS, Qi LS*. CRISPR interference (CRISPRi) for sequence-specific control of gene expression. Nat. Protoc. 8: 2108-2196. 2013 Nov. (Protocol) 9. Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weissman JS, Qi LS. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154: 442-451. 2013 Jul 18. 8. Qi LS*, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152: 1173-1183. 2013 Feb 28. (*Corresponding author) The Top 10 downloaded article in Cell 2013. 7. Liu CC#, Qi LS#, Lucks JB, Segall-Shapiro TH, Wang D, Mutalik VM, Arkin AP. An adaptor from translational to transcriptional control enables predictable assembly of complex regulation. Nat. Methods 9: 1088-1094. 2012 Nov. (#Equal contribution) 6. Qi LS, Haurwitz RE, Shao WJ, Doudna JA, Arkin AP. RNA processing enables predictable programming of gene expression. Nat. Biotechnol. 30: 1002-1006. 2012 Oct. 5. Qi LS, Lucks JB, Liu CC, Mutalik VK, Arkin AP. Engineering naturally occurring trans-acting non-coding RNAs to sense molecular signals. Nucleic Acids Res. 40: 5775-5786. 2012 Jul. 4. Mutalik VK#, Qi LS#, Guimaraes JC, Lucks JB, Arkin AP. Rationally designed families of orthogonal RNA regulators of translation. Nat. Chem. Biol. 8: 447-454. 2012 Mar 25. (#Equal contribution) 3. Lucks JB#, Qi LS#, Mutalik VK, Wang D, Arkin AP. Versatile RNA-sensing transcriptional regulators for engineering genetic networks. Proc. Natl Acad. Sci. USA 108:8617-8822. 2011 May 24. (#Equal contribution) 2. Liu CC, Qi LS, Yanofsky C, Arkin AP. Regulation of transcription by unnatural amino acids. Nat. Biotechnol. 29:164-168. 2011 Feb. 1. Lucks JB, Qi LS, Whitaker WR, Arkin AP. Toward scalable parts families for predictable design of biological circuits. Curr. Opin. Microbiol. 11:567-573. 2008 Dec. (Review)