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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. Cable J, Leonard JN, Lu TK, Xie Z, Chang MW, Fern?ndez L?, 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
  11. 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
  12. 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. SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Sci Transl Med. 2021 04 28; 13(591).  View on PubMed
  13. 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. DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation. Nat Nanotechnol. 2021 02; 16(2):214-223.  View on PubMed
  14. 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. Precise T cell recognition programs designed by transcriptionally linking multiple receptors. Science. 2020 11 27; 370(6520):1099-1104.  View on PubMed
  15. 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. IMMU-33. MULTI-ANTIGEN RECOGNITION CIRCUITS OVERCOME CHALLENGES OF SPECIFICITY, HETEROGENEITY, AND DURABILITY IN T-CELL THERAPY FOR GLIOBLASTOMA. Neuro-Oncology. 2020 Nov 9; 22(Supplement_2):ii111-ii112.  View on PubMed
  16. August Dietrich, Cassandra Burnett, Thomas Martin, Arun Wiita, Kole Roybal, Justin Eyquem. MM-378: Inhibitory and Stimulatory Interplay Between Myeloma Tumor and T Cells. Clinical Lymphoma Myeloma & Leukemia. 2020 Sep 1; 20:s309.  View on PubMed
  17. 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. CRISPR-based screens uncover determinants of immunotherapy response in multiple myeloma. Blood Adv. 2020 07 14; 4(13):2899-2911.  View on PubMed
  18. Landgraf KE, Williams SR, Steiger D, Gebhart D, Lok S, Martin DW, Roybal KT, Kim KC. convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting. Commun Biol. 2020 06 09; 3(1):296.  View on PubMed
  19. 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. 2020 04 30; 181(3):728-744.e21.  View on PubMed
  20. Payal Watchmaker, Joseph Choe, Diego Carrera, Ryan Gilbert, Wei Yu, Kira Downey, Kole Roybal, Wendell Lim, Hideho Okada. IMMU-21. SEQUENTIAL TWO-RECEPTOR PRIMING CAR SYSTEM TO OVERCOME HETEROGENEOUS ANTIGEN EXPRESSION. Neuro-Oncology. 2019 Nov 11; 21(Supplement_6):vi123-vi123.  View on PubMed

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