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

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