Dr. Eric Shifrut

I completed my undergraduate studies in Life and Medical Sciences at Tel Aviv University. For my graduate work, I trained with the late Prof. Nir Friedman at the Weizmann Institute of Science. We mapped the TCR repertoire in health and disease by developing new technological platforms and applying quantitative analytical frameworks.

For my postdoctoral work, I joined Alex Marson at UCSF and Gladstone Institutes to pioneer CRISPR discovery platforms to study primary human T cells. Today, I am excited by the mission to leverage these achievements in CRISPR engineering to design best-in-class T cell therapies against cancer.

The mission of the Shifrut lab is to accelerate the design of breakthrough cell-based therapies by leveraging high throughput discovery platforms to engineer immune cells that function in suppressive tumor environments. The lab studies the biology of primary human T cells from healthy donors, using large scale CRISPR genetic screens, scRNA-Seq and high throughput microscopy.

We use lentiviral vectors, precise knock-in by HDR and advanced experimental tools to map genetic programs that control anti-tumor immunity. The lab aims to test promising candidate perturbations in preclinical animal models of cancer immunology. We will focus on these main research themes:

• Define immunosuppressive signals shaping tumor-reactive T cell immunity
• Interrogate polyclonal responses by engineering TCR repertoires
• Delineate roles of self-reactive T cells in homeostasis and immunotherapy

Find out more by visiting our lab website: www.shifrut-lab.org

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. Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies. Cell. 181(3):728-744.e21. (2020)

https://doi.org/10.1016/j.cell.2020.03.039
 

Cortez J^, Montauti E^, Shifrut E, Zhang Y, Shaked O, Xu Y, Simeonov D, Zhang Y, Roth T, Chen S, Vogel I, Prator G, Zhang B, Lee Y, Sun Z, Ifergan I, Van Gool F, Bluestone J, Fang D*, Marson A*. CRISPR Screen in Regulatory T Cells Reveals Ubiquitination Modulators of Foxp3. Nature. 582(7812):416-420. (2020) https://doi.org/10.1038/s41586-020-2246-4

Shifrut, E.^, Carnevale, J.^, Tobin, V., Roth, T. L., Woo, J. M., Bui, C., Li, P. J., Diolaiti, M., Ashworth, A., Marson, A*. Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function. Cell 175, 1958–1971.e15 (2018). https://doi.org/10.1016/j.cell.2018.10.024

Madi, A.^, Shifrut, E.^, Reich-Zeliger, S., Gal, H., Best, K., Ndifon, W., Chain, B., Cohen, I. R., Friedman, N. T-cell receptor repertoires share a restricted set of public and abundant CDR3 sequences that are associated with self-related immunity. Genome Res. 24, 1603–1612 (2014). https://doi.org/10.1101/gr.170753.113