Frontiers of Science: Reprogramming T Cells with CRISPR

    Associate Prof. Alexander Marson, University of California, San Francisco, US

    host: Riitta Lahesmaa (riitta.lahesmaa@utu.fi)

     

    The goal of Marson’s lab is to understand genetic circuits that control human immune cell function in health and disease. They employ genomic techniques to map epigenetic circuits that establish highly specialized cell identities. Marson’s team have begun to identify autoimmunity risk variants that disrupt immune cell circuits, and how pathogenic circuits may be targeted with novel therapeutics. His lab has developed new tools for CRISPR genome engineering in primary human T cells and they are now pursuing a comprehensive strategy to test how coding and non-coding genetic variation controls functional programs in the immune system. Genome engineered human T cells hold great potential for the next generation of cell-based therapies for cancer, autoimmunity, and infectious diseases.

     

    Selected publications

    Roth TL, Li PJ, Blaeschke F, Nies JF, Apathy R, Mowery C, Yu R, Nguyen MLT, Lee Y, Truong A, Hiatt J, Wu D, Nguyen DN, Goodman D, Bluestone JA, Ye CJ, Roybal K, Shifrut E, Marson A. 2020. Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies. Cell. 181: 728-744.e21.
    https://dx.doi.org/10.1016/j.cell.2020.03.039

    Nguyen DN, Roth TL, Li PJ, Chen PA, Apathy R, Mamedov MR, Vo LT, Tobin VR, Goodman D, Shifrut E, Bluestone JA, Puck JM, Szoka FC, Marson A. 2020. Polymer-stabilized Cas9 nanoparticles and modified repair templates increase genome editing efficiency. Nat Biotechnol. 38: 44-49
    https://dx.doi.org/10.1038/s41587-019-0325-6

    Shifrut E, Carnevale J, Tobin V, Roth TL, Woo JM, Bui CT, Li PJ, Diolaiti ME, Ashworth A, Marson A. 2018. Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function. Cell. 175: 1958-1971.e15
    https://dx.doi.org/10.1016/j.cell.2018.10.024

    Roth TL, Puig-Saus C, Yu R, Shifrut E, Carnevale J, Li PJ, Hiatt J, Saco J, Krystofinski P, Li H, Tobin V, Nguyen DN, Lee MR, Putnam AL, Ferris AL, Chen JW, Schickel JN, Pellerin L, Carmody D, Alkorta-Aranburu G, Del Gaudio D, Matsumoto H, Morell M, Mao Y, Cho M, Quadros RM, Gurumurthy CB, Smith B, Haugwitz M, Hughes SH, Weissman JS, Schumann K, Esensten JH, May AP, Ashworth A, Kupfer GM, Greeley SAW, Bacchetta R, Meffre E, Roncarolo MG, Romberg N, Herold KC, Ribas A, Leonetti MD, Marson A. 2018. Reprogramming human T cell function and specificity with non-viral genome targeting. Nature 559: 405-409
    https://dx.doi.org/10.1038/s41586-018-0326-5

    Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE, Haliburton GE, Ye CJ, Bluestone JA, Doudna JA, Marson A. 2015. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc Natl Acad Sci U S A 112: 10437-42
    https://dx.doi.org/10.1073/pnas.1512503112

     

    Genral info regarding the Frontiers of Science eTALKs

    • Registration is obligatory and links to register will be provided in BioCity Turku webpage (https://biocityturku.fi/biocityevents/frontiers-of-science-seminars/programme-autumn-2020/) and in BioCity Turku news feed, few weeks before the event.
    • Registration closes two days before the event and link to join zoom will be sent to the participants one day in advance.
    • Microphones and cameras need to be turned off during the presentation, but the audience is welcome to ask questions after the talk, preferably with video turned on to make the discussion as interactive as possible.
    • If you are a student and need a certificate for your attendance, please fill in your student number when registering to the events. After the seminar season is over, please contact BioCity Turku coordinator biocityturku@bioscience.fi.

    If you have any questions regarding our Frontiers of Science eTALK seminar series, please don’t hesitate to contact BioCity Turku coordinator biocityturku@bioscience.fi