Research Summary

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. 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.

Education

Austin College, B.A., 05/2005, Biology
UT Southwestern Medical Center at Dallas, Ph.D., 01/2013, Molecular Immunology

Honors & Awards

  • 2007
    Ruth L. Kirschstein National Research Service Award, National Institutes of Health
  • 2011
    Eliot Golding’s Award for thesis in Immunology, UT Southwestern Medical Center
  • 2012
    Dean’s Award for Academic and Research Excellence, UT Southwestern Medical Center
  • 2016
    Keynote Address at the UAB Comprehensive Cancer Center Retreat
  • 2017
    Named to first cohort of Chan Zuckerberg Biohub Investigators

Selected Publications

  1. Zachary Steinhart, Jeffrey Perera, Dmytro Dorovskyi, Luke Workley, Carinna Tran, Rosmely Hernandez, Zhongmei Li, Max Foisey, Daniel Goodman, Kole Roybal, Brian Shy, Alexander Marson. Abstract A026: Deciphering natural and synthetic genetic programs governing human T cell function with combinatorial CRISPR activation and interference screens. Cancer Immunology Research. 2025 Feb 23; 13(2_Supplement):a026-a026.  View on PubMed
  2. Piraner DI, Abedi MH, Duran Gonzalez MJ, Chazin-Gray A, Lin A, Zhu I, Ravindran PT, Schlichthaerle T, Huang B, Bearchild TH, Lee D, Wyman S, Jun YW, Baker D, Roybal KT. Engineered receptors for soluble cellular communication and disease sensing. Nature. 2025 Feb; 638(8051):805-813.  View on PubMed
  3. Huang B, Abedi M, Ahn G, Coventry B, Sappington I, Tang C, 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, Yi L, Yeh R, Misquith A, Wolf A, Tomasovic LM, Piraner DI, Duran Gonzalez MJ, Bennett NR, Venkatesh P, Ahlrichs M, Dobbins C, Yang W, Wang X, Sahtoe DD, Vafeados D, Mout R, Shivaei S, Cao L, Carter L, Stewart L, Spangler JB, Roybal KT, Greisen PJ, Li X, Bernardes GJL, Bertozzi CR, Baker D. Designed endocytosis-inducing proteins degrade targets and amplify signals. Nature. 2025 Feb; 638(8051):796-804.  View on PubMed
  4. Ledergor G, Fan Z, Wu K, McCarthy E, Hyrenius-Wittsten A, Starzinski A, Chang H, Bridge M, Kwek S, Cheung A, Bylsma S, Hansen E, Wolf J, Wong S, Shah N, Roybal KT, Martin T, Ye CJ, Fong L. CD4+ CAR T-cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR T-cell therapy. Blood Adv. 2024 07 09; 8(13):3562-3575.  View on PubMed
  5. 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 T cell mutations enhance engineered T cell therapies. Nature. 2024 Feb; 626(7999):626-634.  View on PubMed
  6. 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, Jaehyuk Choi. Naturally Occurring Mutations in Human T Cell Lymphomas Enhance Engineered T Cell Therapies. Blood. 2023 Nov 28; 142(Supplement 1):884.  View on PubMed
  7. 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, Wolf A, Tomasovic LM, Piraner DI, Gonzalez MJD, Bennett NR, Venkatesh P, Satoe D, Ahlrichs M, Dobbins C, Yang W, Wang X, Vafeados D, Mout R, Shivaei S, Cao L, Carter L, Stewart L, Spangler JB, Bernardes GJL, Roybal KT, Greisen P, Li X, Bertozzi C, Baker D. Designed Endocytosis-Triggering Proteins mediate Targeted Degradation. bioRxiv. 2023 Sep 20.  View on PubMed
  8. Zhu I, Piraner DI, Roybal KT. Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies. Cancer Immunol Res. 2023 08 03; 11(8):1030-1043.  View on PubMed
  9. Garcia JM, Burnett CE, Roybal KT. Toward the clinical development of synthetic immunity to cancer. Immunol Rev. 2023 11; 320(1):83-99.  View on PubMed
  10. 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. Synthetic cytokine circuits that drive T cells into immune-excluded tumors. Science. 2022 12 16; 378(6625):eaba1624.  View on PubMed
  11. Beppler C, Eichorst J, Marchuk K, Cai E, Castellanos CA, Sriram V, Roybal KT, Krummel MF. Hyperstabilization of T cell microvilli contacts by chimeric antigen receptors. J Cell Biol. 2023 03 06; 222(3).  View on PubMed
  12. Li HS, Israni DV, Gagnon KA, Gan KA, Raymond MH, Sander JD, Roybal KT, Joung JK, Wong WW, Khalil AS. Multidimensional control of therapeutic human cell function with synthetic gene circuits. Science. 2022 12 16; 378(6625):1227-1234.  View on PubMed
  13. 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. Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies. Sci Transl Med. 2022 11 09; 14(670):eabm1463.  View on PubMed
  14. Shemesh A, Su Y, Calabrese DR, Chen D, Arakawa-Hoyt J, Roybal KT, Heath JR, Greenland JR, Lanier LL. Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression. J Exp Med. 2022 11 07; 219(11).  View on PubMed
  15. 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. Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma. J Nucl Med. 2023 01; 64(1):137-144.  View on PubMed
  16. Shemesh A, Pickering H, Roybal KT, Lanier LL. Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion. J Exp Med. 2022 08 01; 219(8).  View on PubMed
  17. Zhu I, Liu R, Garcia JM, Hyrenius-Wittsten A, Piraner DI, Alavi J, Israni DV, Liu B, Khalil AS, Roybal KT. Modular design of synthetic receptors for programmed gene regulation in cell therapies. Cell. 2022 04 14; 185(8):1431-1443.e16.  View on PubMed
  18. Kole T. Roybal, Hanin Alamir, Jiahe Lu, Christoph Wülfing. Cellular Structures Controlling T Cell Signaling in Time and Space. . 2022 Jan 1; (Annu Rev Immunol 36 2018).  View on PubMed
  19. 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. Synthetic biology: at the crossroads of genetic engineering and human therapeutics-a Keystone Symposia report. Ann N Y Acad Sci. 2021 12; 1506(1):98-117.  View on PubMed
  20. Hyrenius-Wittsten A, Su Y, Park M, Garcia JM, Alavi J, Perry N, Montgomery G, Liu B, Roybal KT. SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models. Sci Transl Med. 2021 04 28; 13(591).  View on PubMed

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