Kole Roybal, PhD
Associate Professor
Microbiology and Immunology
School of Medicine
In the Roybal Lab we harness the tools of synthetic and chemical biology to enhance the therapeutic potential of engineered immune cells. We take a comprehensive approach to cellular engineering by developing new synthetic receptors, signal transduction cascades, and cellular response programs to enhance the safety and effectiveness of adoptive cell therapies.
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We also study the logic of natural cellular signaling systems, and the underlying principles of cellular communication and collective cell behavior during an immune response.
Awards
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- NIH New Innovator Award, NIH - National Cancer Institute, 2018-2023
- Award for Regenerative Medicine and Cell Therapy, Science Magazine & Sartorius, 2018
- Chan Zuckerberg Biohub Investigator, Chan Zuckerberg Biohub, 2017
- Member Researcher, Parker Institute for Cancer Immunotherapy, 2017
- Postdoctoral Fellowship, Jane Coffin Childs Memorial Fund, 2014-2017
- Ruth L. Kirschstein National Research Service Award, National Institutes of Health, 2007-2010
Education & Training
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- Ph.D. Immunology UT Southwestern Medical Center 2013
- B.A. Biology Austin College 2005
Websites
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- Roybal Lab Website (roybal-lab.org)
- Parker Institute for Cancer Immunotherapy (parkerici.org)
- UCSF Department of Microbiology and Immunology (microbiology.ucsf.edu)
- Chan Zuckerberg BioHub (czbiohub.org)
- UCSF Immunology Program (immunology.ucsf.edu)
Videos
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- Cell Paperflick on Synthetic Notch Receptors (youtube.com)
Publications (60)
Top publication keywords:
Hematologic NeoplasmsNeoplasmsCell EngineeringT-LymphocytesSynthetic BiologyReceptors, NotchCell- and Tissue-Based TherapyAntigen-Presenting CellsLymphocyte ActivationReceptors, ArtificialActinsReceptors, Antigen, T-CellImmunotherapyActin Depolymerizing FactorsImmunotherapy, Adoptive
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Modular design of synthetic receptors for programmed gene regulation in cell therapies.
Cell 2022 Zhu I, Liu R, Garcia JM, Hyrenius-Wittsten A, Piraner DI, Alavi J, Israni DV, Liu B, Khalil AS, Roybal KT -
SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models.
Science translational medicine 2021 Hyrenius-Wittsten A, Su Y, Park M, Garcia JM, Alavi J, Perry N, Montgomery G, Liu B, Roybal KT -
SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma.
Science translational medicine 2021 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… -
Precise T cell recognition programs designed by transcriptionally linking multiple receptors.
Science (New York, N.Y.) 2020 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 -
CD4+ CAR-T cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR-T cell therapy.
Blood advances 2024 Ledergor G, Fan Z, Wu K, McCarthy E, Hyrenius-Wittsten A, Starzinski A, Chang H, Bridge M, Kwek SS, Cheung A, Bylsma SA, Hansen E, Wolf JL, Wong SW, Shah N, Roybal KT, Martin TG, Ye CJ, Fong L
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Naturally occurring T cell mutations enhance engineered T cell therapies.
Nature 2024 Garcia J, Daniels J, Lee Y, Zhu I, Cheng K, Liu Q, Goodman D, Burnett C, Law C, Thienpont C, Alavi J, Azimi C, Montgomery G, Roybal KT, Choi J -
Naturally Occurring Mutations in Human T Cell Lymphomas Enhance Engineered T Cell Therapies.
Blood 2023 Julie Garcia, Jay Daniels, Yujin Lee, Iowis Zhu, Kathleen Cheng, Qing Liu, Daniel Goodman, Cassandra Burnett, Calvin Law, Chloe Thienpoint, Josef Alavi, Camillia Azimi, Garrett Montgomery, Kole Roybal… -
Designed Endocytosis-Triggering Proteins mediate Targeted Degradation.
bioRxiv : the preprint server for biology 2023 Huang B, Abedi M, Ahn G, Coventry B, Sappington I, Wang R, Schlichthaerle T, Zhang JZ, Wang Y, Goreshnik I, Chiu CW, Chazin-Gray A, Chan S, Gerben S, Murray A, Wang S, O'Neill J, Yeh R, Misquith A, … -
Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies.
Cancer immunology research 2023 Zhu I, Piraner DI, Roybal KT -
Toward the clinical development of synthetic immunity to cancer.
Immunological reviews 2023 Garcia JM, Burnett CE, Roybal KT -
Synthetic cytokine circuits that drive T cells into immune-excluded tumors.
Science (New York, N.Y.) 2022 Allen GM, Frankel NW, Reddy NR, Bhargava HK, Yoshida MA, Stark SR, Purl M, Lee J, Yee JL, Yu W, Li AW, Garcia KC, El-Samad H, Roybal KT, Spitzer MH, Lim WA -
Hyperstabilization of T cell microvilli contacts by chimeric antigen receptors.
The Journal of cell biology 2022 Beppler C, Eichorst J, Marchuk K, Cai E, Castellanos CA, Sriram V, Roybal KT, Krummel MF -
Multidimensional control of therapeutic human cell function with synthetic gene circuits.
Science (New York, N.Y.) 2022 Li HS, Israni DV, Gagnon KA, Gan KA, Raymond MH, Sander JD, Roybal KT, Joung JK, Wong WW, Khalil AS -
Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies.
Science translational medicine 2022 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 -
Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression.
The Journal of experimental medicine 2022 Shemesh A, Su Y, Calabrese DR, Chen D, Arakawa-Hoyt J, Roybal KT, Heath JR, Greenland JR, Lanier LL -
Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2022 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 -
Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion.
The Journal of experimental medicine 2022 Shemesh A, Pickering H, Roybal KT, Lanier LL -
Cellular Structures Controlling T Cell Signaling in Time and Space.
2022 Kole T. Roybal, Hanin Alamir, Jiahe Lu, Christoph Wülfing -
Synthetic biology: at the crossroads of genetic engineering and human therapeutics-a Keystone Symposia report.
Annals of the New York Academy of Sciences 2021 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… -
DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation.
Nature nanotechnology 2020 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 -
IMMU-33. MULTI-ANTIGEN RECOGNITION CIRCUITS OVERCOME CHALLENGES OF SPECIFICITY, HETEROGENEITY, AND DURABILITY IN T-CELL THERAPY FOR GLIOBLASTOMA.
Neuro-Oncology 2020 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, … -
MM-378: Inhibitory and Stimulatory Interplay Between Myeloma Tumor and T Cells.
Clinical Lymphoma Myeloma & Leukemia 2020 August Dietrich, Cassandra Burnett, Thomas Martin, Arun Wiita, Kole Roybal, Justin Eyquem -
CRISPR-based screens uncover determinants of immunotherapy response in multiple myeloma.
Blood advances 2020 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 -
convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting.
Communications biology 2020 Landgraf KE, Williams SR, Steiger D, Gebhart D, Lok S, Martin DW, Roybal KT, Kim KC -
Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies.
Cell 2020 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 -
IMMU-21. SEQUENTIAL TWO-RECEPTOR PRIMING CAR SYSTEM TO OVERCOME HETEROGENEOUS ANTIGEN EXPRESSION.
Neuro-Oncology 2019 Payal Watchmaker, Joseph Choe, Diego Carrera, Ryan Gilbert, Wei Yu, Kira Downey, Kole Roybal, Wendell Lim, Hideho Okada -
Paving New Roads for CARs.
Trends in cancer 2019 Hyrenius-Wittsten A, Roybal KT -
NextGen cell-based immunotherapies in cancer and other immune disorders.
Current opinion in immunology 2019 Azimi CS, Tang Q, Roybal KT, Bluestone JA -
Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade.
Immunity 2019 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… -
Abstract B044: Engineering CAR NK cells for antigen-dependent autocrine expansion.
Convergence of Technology and Cancer Immunotherapy 2019 Avishai Shemesh, Kole T. Roybal, Lewis L. Lanier -
Beyond the TCR, Antigen Discrimination in T Cells Continues in the LAT:GRB2:SOS Protein Condensate.
Biophysical Journal 2019 Shalini T. Low-Nam, Jenny JY Lin, Darren B. McAffee, Steven A. Alvarez, Scott D. Hansen, Kole T. Roybal, Jay T. Groves -
Identifying Factors in Multiple Myeloma Controlling Response to B-Cell Maturation Antigen (BCMA)-Targeted Immunotherapy Using CRISPR-Based Functional Genomics.
Blood 2018 Poornima Ramkumar, Jaime Leong, Meghan Seyler, Stratton J Georgoulis, Axel Hyrenius Wittsten, Priya Choudhry, Kole Roybal, Arun P Wiita, Martin Kampmann -
IMMU-57. SEQUENTIAL TWO-RECEPTOR PRIMING CAR SYSTEM TO OVERCOME HETEROGENEOUS ANTIGEN EXPRESSION.
Neuro-Oncology 2018 Payal Watchmaker, Joseph Choe, Diego Carrera, Kira Downey, Maryam Shahin, Kole Roybal, Wendell Lim, Hideho Okada -
Abstract 2981: Clonal deletion of tumor-specific T cells by combination checkpoint blockade compromises antitumor efficacy in low tumor burden states.
Immunology 2018 Chien-Chun Steven Pai, Xiaoqing Lu, Donald Simons, Michel DuPage, Kole T. Roybal, Mingyi Chen, Serena Kwek, Amy-Jo Casbon, Gillian A. Kinsbury, Lawrence Fong -
Refining cell therapy.
Science (New York, N.Y.) 2018 Roybal KT -
Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.
Annual review of immunology 2017 Roybal KT, Lim WA -
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells.
Scientific reports 2017 Rupp LJ, Schumann K, Roybal KT, Gate RE, Ye CJ, Lim WA, Marson A -
Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors.
Cell 2016 Roybal KT, Williams JZ, Morsut L, Rupp LJ, Kolinko I, Choe JH, Walker WJ, McNally KA, Lim WA -
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells.
The Journal of Immunology 2016 Levi Rupp, Kathrin Schumann, Kole T Roybal, Alexander Marson, Wendell A Lim -
Computational spatiotemporal analysis identifies WAVE2 and cofilin as joint regulators of costimulation-mediated T cell actin dynamics.
Science signaling 2016 Roybal KT, Buck TE, Ruan X, Cho BH, Clark DJ, Ambler R, Tunbridge HM, Zhang J, Verkade P, Wülfing C, Murphy RF -
Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors.
Cell 2016 Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM, Thomson M, Lim WA -
Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits.
Cell 2016 Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA, Park JS, Lim WA -
Cellular Structures Controlling T Cell Signaling in Time and Space.
Encyclopedia of Cell Biology 2016 C. Wülfing, K.T. Roybal -
Remote control of therapeutic T cells through a small molecule-gated chimeric receptor.
Science (New York, N.Y.) 2015 Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA -
Early Signaling in Primary T Cells Activated by Antigen Presenting Cells Is Associated with a Deep and Transient Lamellal Actin Network.
PloS one 2015 Roybal KT, Mace EM, Mantell JM, Verkade P, Orange JS, Wülfing C -
Modest Interference with Actin Dynamics in Primary T Cell Activation by Antigen Presenting Cells Preferentially Affects Lamellal Signaling.
PloS one 2015 Roybal KT, Mace EM, Clark DJ, Leard AD, Herman A, Verkade P, Orange JS, Wülfing C -
Synthetic biology approaches to engineer T cells.
Current opinion in immunology 2015 Wu CY, Rupp LJ, Roybal KT, Lim WA -
Cellular structures controlling T cell signaling in time and space
Encyclopedia of Cell Biology 2015 Wülfing C, Roybal KT -
IFN-α suppresses GATA3 transcription from a distal exon and promotes H3K27 trimethylation of the CNS-1 enhancer in human Th2 cells.
Journal of immunology (Baltimore, Md. : 1950) 2014 Huber JP, Gonzales-van Horn SR, Roybal KT, Gill MA, Farrar JD -
Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc receptors.
mAbs 2014 Furlan SN, Mandraju R, Brewer T, Roybal K, Troutman TD, Hu W, Palm NW, Unni A, Pasare C -
The actin-driven spatiotemporal organization of T-cell signaling at the system scale.
Immunological reviews 2013 Roybal KT, Sinai P, Verkade P, Murphy RF, Wülfing C -
Differential regulation of the period genes in striatal regions following cocaine exposure.
PloS one 2013 Falcon E, Ozburn A, Mukherjee S, Roybal K, McClung CA -
New TACTICS for finding Numb.
Immunology and cell biology 2012 Roybal KT, Wülfing C -
Mycobacterial shuttle vectors designed for high-level protein expression in infected macrophages.
Applied and environmental microbiology 2012 Eitson JL, Medeiros JJ, Hoover AR, Srivastava S, Roybal KT, Aínsa JA, Hansen EJ, Gumbo T, van Oers NS -
The CD3 zeta subunit contains a phosphoinositide-binding motif that is required for the stable accumulation of TCR-CD3 complex at the immunological synapse.
Journal of immunology (Baltimore, Md. : 1950) 2011 DeFord-Watts LM, Dougall DS, Belkaya S, Johnson BA, Eitson JL, Roybal KT, Barylko B, Albanesi JP, Wülfing C, van Oers NS -
Tentative and transient natural killer cell polarization balances the requirements for discriminatory recognition and cytolytic efficacy.
Communicative & integrative biology 2010 Sinai P, Roybal KT, Wülfing C -
Inhibiting the inhibitor of the inhibitor: blocking PKC-theta to enhance regulatory T cell function.
Science signaling 2010 Roybal KT, Wülfing C -
Spatiotemporal patterning during T cell activation is highly diverse.
Science signaling 2009 Singleton KL, Roybal KT, Sun Y, Fu G, Gascoigne NR, van Oers NS, Wülfing C -
Spatiotemporal patterning of T cell signaling as an important regulator of T cell activation at the systems level.
The FASEB Journal 2008 Christoph Wuelfing, Kentner L. Singleton, Kole T. Roybal, Yi Sun -
Mania-like behavior induced by disruption of CLOCK.
Proceedings of the National Academy of Sciences of the United States of America 2007 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