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EmailKole Roybal, PhD, is an affiliate investigator at Gladstone Institutes. He is also an associate professor of microbiology and immunology at UC San Francisco (UCSF), a Chan Zuckerberg Biohub investigator, and a Parker Institute for Cancer Immunotherapy investigator.
Roybal earned a PhD in immunology from the University of Texas Southwestern Medical Center, and trained as a postdoctoral fellow in cell and molecular pharmacology at UCSF. He joined the UCSF faculty as an assistant professor in 2017, and the UCSF-Gladstone Institute of Genomic Immunology in 2022.
Roybal harnesses the tools of synthetic and chemical biology to increase the therapeutic potential of engineered immune cells. Working at every step along the cascade of events that mediate the killing of cancer cells by therapeutic T cells (CAR-T cells), he seeks to optimize the initial sensing of cancer cells by CAR-T cells, as well as the efficacy and safety of the subsequent cancer cell elimination. He also studies the intercellular communication and collective cellular behaviors underlying the immune response.
He was awarded the 2018 Science Magazine and Sartorius Prize for Regenerative Medicine and Cell Therapy and received a New Innovator Award from National Institutes of Health in 2018.
Publications
- Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies. Goodman DB, Azimi CS, Kearns K, Talbot A, Garakani K, Garcia J, Patel N, Hwang B, Lee D, Park E, Vykunta VS, Shy BR, Ye CJ, Eyquem J, Marson A, Bluestone JA, Roybal KT. Sci Transl Med. 2022 Nov 09; 14(670):eabm1463.
- Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression. Shemesh A, Su Y, Calabrese DR, Chen D, Arakawa-Hoyt J, Roybal KT, Heath JR, Greenland JR, Lanier LL. J Exp Med. 2022 11 07; 219(11).
- Antigen-dependent inducible T cell reporter system for PET imaging of breast cancer and glioblastoma. Shin J, Parker MFL, Zhu I, Alanizi A, Rodriguez CI, Liu R, Watchmaker PB, Kalita M, Blecha J, Luu J, Wright B, Lapi SE, Flavell RR, Okada H, Tlsty TD, Roybal KT, Wilson DM. J Nucl Med. 2022 Aug 18.
- Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion. Shemesh A, Pickering H, Roybal KT, Lanier LL. J Exp Med. 2022 08 01; 219(8).
- Modular design of synthetic receptors for programmed gene regulation in cell therapies. Zhu I, Liu R, Garcia JM, Hyrenius-Wittsten A, Piraner DI, Alavi J, Israni DV, Liu B, Khalil AS, Roybal KT. Cell. 2022 04 14; 185(8):1431-1443.e16.
- Cellular Structures Controlling T Cell Signaling in Time and Space. Kole T. Roybal, Hanin Alamir, Jiahe Lu, Christoph Wülfing. . 2022 Jan 1; (Annu Rev Immunol 36 2018).
- Synthetic biology: at the crossroads of genetic engineering and human therapeutics-a Keystone Symposia report. Cable J, Leonard JN, Lu TK, Xie Z, Chang MW, Fernández LÁ, Lora JM, Kaufman HL, Quintana FJ, Geiger R, F Lesser C, Lynch JP, Hava DL, Cornish VW, Lee GK, DiAndreth B, Fero M, Srivastava R, De Coster T, Roybal KT, Rackham OJL, Kiani S, Zhu I, Hernandez-Lopez RA, Guo T, Chen WCW. Ann N Y Acad Sci. 2021 12; 1506(1):98-117.
- SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models. Hyrenius-Wittsten A, Su Y, Park M, Garcia JM, Alavi J, Perry N, Montgomery G, Liu B, Roybal KT. Sci Transl Med. 2021 04 28; 13(591).
- SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Choe JH, Watchmaker PB, Simic MS, Gilbert RD, Li AW, Krasnow NA, Downey KM, Yu W, Carrera DA, Celli A, Cho J, Briones JD, Duecker JM, Goretsky YE, Dannenfelser R, Cardarelli L, Troyanskaya O, Sidhu SS, Roybal KT, Okada H, Lim WA. Sci Transl Med. 2021 04 28; 13(591).
- DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation. Huang X, Williams JZ, Chang R, Li Z, Burnett CE, Hernandez-Lopez R, Setiady I, Gai E, Patterson DM, Yu W, Roybal KT, Lim WA, Desai TA. Nat Nanotechnol. 2021 02; 16(2):214-223.
- Precise T cell recognition programs designed by transcriptionally linking multiple receptors. Williams JZ, Allen GM, Shah D, Sterin IS, Kim KH, Garcia VP, Shavey GE, Yu W, Puig-Saus C, Tsoi J, Ribas A, Roybal KT, Lim WA. Science. 2020 11 27; 370(6520):1099-1104.
- IMMU-33. MULTI-ANTIGEN RECOGNITION CIRCUITS OVERCOME CHALLENGES OF SPECIFICITY, HETEROGENEITY, AND DURABILITY IN T-CELL THERAPY FOR GLIOBLASTOMA. Payal Watchmaker, Joseph Choe, Milos Simic, Ryan Gilbert, Aileen li, Nira Krasnow, Diego Carrera, Wei Yu, Kira Downey, Anna Celli, Juhyun Cho, Jessica Briones, Ruth Dannenfelser, Lia Cardarelli, Sachdev Sidhu, Kole Roybal, Wendell Lim, Hideho Okada. Neuro-Oncology. 2020 Nov 9; 22(Supplement_2):ii111-ii112.
- MM-378: Inhibitory and Stimulatory Interplay Between Myeloma Tumor and T Cells. August Dietrich, Cassandra Burnett, Thomas Martin, Arun Wiita, Kole Roybal, Justin Eyquem. Clinical Lymphoma Myeloma & Leukemia. 2020 Sep 1; 20:s309.
- CRISPR-based screens uncover determinants of immunotherapy response in multiple myeloma. Ramkumar P, Abarientos AB, Tian R, Seyler M, Leong JT, Chen M, Choudhry P, Hechler T, Shah N, Wong SW, Martin TG, Wolf JL, Roybal KT, Pahl A, Taunton J, Wiita AP, Kampmann M. Blood Adv. 2020 07 14; 4(13):2899-2911.
- convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting. Landgraf KE, Williams SR, Steiger D, Gebhart D, Lok S, Martin DW, Roybal KT, Kim KC. Commun Biol. 2020 06 09; 3(1):296.
- Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies. 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. Cell. 2020 04 30; 181(3):728-744.e21.
- IMMU-21. SEQUENTIAL TWO-RECEPTOR PRIMING CAR SYSTEM TO OVERCOME HETEROGENEOUS ANTIGEN EXPRESSION. Payal Watchmaker, Joseph Choe, Diego Carrera, Ryan Gilbert, Wei Yu, Kira Downey, Kole Roybal, Wendell Lim, Hideho Okada. Neuro-Oncology. 2019 Nov 11; 21(Supplement_6):vi123-vi123.
- Paving New Roads for CARs. Hyrenius-Wittsten A, Roybal KT. Trends Cancer. 2019 10; 5(10):583-592.
- NextGen cell-based immunotherapies in cancer and other immune disorders. Azimi CS, Tang Q, Roybal KT, Bluestone JA. Curr Opin Immunol. 2019 08; 59:79-87.
- Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade. Pai CS, Huang JT, Lu X, Simons DM, Park C, Chang A, Tamaki W, Liu E, Roybal KT, Seagal J, Chen M, Hagihara K, Wei XX, DuPage M, Kwek SS, Oh DY, Daud A, Tsai KK, Wu C, Zhang L, Fasso M, Sachidanandam R, Jayaprakash A, Lin I, Casbon AJ, Kinsbury GA, Fong L. Immunity. 2019 02 19; 50(2):477-492.e8.
- Beyond the TCR, Antigen Discrimination in T Cells Continues in the LAT:GRB2:SOS Protein Condensate. Shalini T. Low-Nam, Jenny JY Lin, Darren B. McAffee, Steven A. Alvarez, Scott D. Hansen, Kole T. Roybal, Jay T. Groves. Biophysical Journal. 2019 Feb 1; 116(3):530a.
- Identifying Factors in Multiple Myeloma Controlling Response to B-Cell Maturation Antigen (BCMA)-Targeted Immunotherapy Using CRISPR-Based Functional Genomics. Poornima Ramkumar, Jaime Leong, Meghan Seyler, Stratton J Georgoulis, Axel Hyrenius Wittsten, Priya Choudhry, Kole Roybal, Arun P Wiita, Martin Kampmann. Blood. 2018 Nov 29; 132(Supplement 1):1926-1926.
- IMMU-57. SEQUENTIAL TWO-RECEPTOR PRIMING CAR SYSTEM TO OVERCOME HETEROGENEOUS ANTIGEN EXPRESSION. Payal Watchmaker, Joseph Choe, Diego Carrera, Kira Downey, Maryam Shahin, Kole Roybal, Wendell Lim, Hideho Okada. Neuro-Oncology. 2018 Nov 5; 20(suppl_6):vi134-vi134.
- Refining cell therapy. Roybal KT. Science. 2018 Mar 09; 359(6380):1112-1113.
- Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities. Roybal KT, Lim WA. Annu Rev Immunol. 2017 04 26; 35:229-253.
- CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Rupp LJ, Schumann K, Roybal KT, Gate RE, Ye CJ, Lim WA, Marson A. Sci Rep. 2017 04 07; 7(1):737.
- Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors. Roybal KT, Williams JZ, Morsut L, Rupp LJ, Kolinko I, Choe JH, Walker WJ, McNally KA, Lim WA. Cell. 2016 Oct 06; 167(2):419-432.e16.
- Computational spatiotemporal analysis identifies WAVE2 and cofilin as joint regulators of costimulation-mediated T cell actin dynamics. Roybal KT, Buck TE, Ruan X, Cho BH, Clark DJ, Ambler R, Tunbridge HM, Zhang J, Verkade P, Wülfing C, Murphy RF. Sci Signal. 2016 Apr 19; 9(424):rs3.
- Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors. Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM, Thomson M, Lim WA. Cell. 2016 Feb 11; 164(4):780-91.
- Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits. Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA, Park JS, Lim WA. Cell. 2016 Feb 11; 164(4):770-9.
- Cellular Structures Controlling T Cell Signaling in Time and Space. C. Wülfing, K.T. Roybal. Encyclopedia of Cell Biology. 2016 Jan 1; 677-686.
- Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA. Science. 2015 Oct 16; 350(6258):aab4077.
- Early Signaling in Primary T Cells Activated by Antigen Presenting Cells Is Associated with a Deep and Transient Lamellal Actin Network. Roybal KT, Mace EM, Mantell JM, Verkade P, Orange JS, Wülfing C. PLoS One. 2015; 10(8):e0133299.
- Modest Interference with Actin Dynamics in Primary T Cell Activation by Antigen Presenting Cells Preferentially Affects Lamellal Signaling. Roybal KT, Mace EM, Clark DJ, Leard AD, Herman A, Verkade P, Orange JS, Wülfing C. PLoS One. 2015; 10(8):e0133231.
- Synthetic biology approaches to engineer T cells. Wu CY, Rupp LJ, Roybal KT, Lim WA. Curr Opin Immunol. 2015 Aug; 35:123-30.
- Cellular structures controlling T cell signaling in time and space Wülfing C, Roybal KT. . Encyclopedia of Cell Biology. 2015; 677-686.
- IFN-α suppresses GATA3 transcription from a distal exon and promotes H3K27 trimethylation of the CNS-1 enhancer in human Th2 cells. Huber JP, Gonzales-van Horn SR, Roybal KT, Gill MA, Farrar JD. J Immunol. 2014 Jun 15; 192(12):5687-94.
- Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc receptors. Furlan SN, Mandraju R, Brewer T, Roybal K, Troutman TD, Hu W, Palm NW, Unni A, Pasare C. MAbs. 2014 Jan-Feb; 6(1):108-18.
- The actin-driven spatiotemporal organization of T-cell signaling at the system scale. Roybal KT, Sinai P, Verkade P, Murphy RF, Wülfing C. Immunol Rev. 2013 Nov; 256(1):133-47.
- Differential regulation of the period genes in striatal regions following cocaine exposure. Falcon E, Ozburn A, Mukherjee S, Roybal K, McClung CA. PLoS One. 2013; 8(6):e66438.
- New TACTICS for finding Numb. Roybal KT, Wülfing C. Immunol Cell Biol. 2013 Jan; 91(1):1-2.
- Mycobacterial shuttle vectors designed for high-level protein expression in infected macrophages. Eitson JL, Medeiros JJ, Hoover AR, Srivastava S, Roybal KT, Aínsa JA, Hansen EJ, Gumbo T, van Oers NS. Appl Environ Microbiol. 2012 Oct; 78(19):6829-37.
- The CD3 zeta subunit contains a phosphoinositide-binding motif that is required for the stable accumulation of TCR-CD3 complex at the immunological synapse. DeFord-Watts LM, Dougall DS, Belkaya S, Johnson BA, Eitson JL, Roybal KT, Barylko B, Albanesi JP, Wülfing C, van Oers NS. J Immunol. 2011 Jun 15; 186(12):6839-47.
- Tentative and transient natural killer cell polarization balances the requirements for discriminatory recognition and cytolytic efficacy. Sinai P, Roybal KT, Wülfing C. Commun Integr Biol. 2010 Nov; 3(6):545-8.
- Inhibiting the inhibitor of the inhibitor: blocking PKC-theta to enhance regulatory T cell function. Roybal KT, Wülfing C. Sci Signal. 2010 Jul 27; 3(132):pe24.
- Spatiotemporal patterning during T cell activation is highly diverse. Singleton KL, Roybal KT, Sun Y, Fu G, Gascoigne NR, van Oers NS, Wülfing C. Sci Signal. 2009 Apr 07; 2(65):ra15.
- Spatiotemporal patterning of T cell signaling as an important regulator of T cell activation at the systems level. Christoph Wuelfing, Kentner L. Singleton, Kole T. Roybal, Yi Sun. The FASEB Journal. 2008 Mar 1; 22:1064.16-1064.16.
- Mania-like behavior induced by disruption of CLOCK. Roybal K, Theobold D, Graham A, DiNieri JA, Russo SJ, Krishnan V, Chakravarty S, Peevey J, Oehrlein N, Birnbaum S, Vitaterna MH, Orsulak P, Takahashi JS, Nestler EJ, Carlezon WA, McClung CA. Proc Natl Acad Sci U S A. 2007 Apr 10; 104(15):6406-11.