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.

Research Funding

  • September 30, 2018 - May 31, 2023 - Engineering the Next-generation of Custom Immune Cell Therapies , Principal Investigator . Sponsor: NIH, Sponsor Award ID: DP2CA239143

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. 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 Apr 14; 185(8):1431-1443.e16.  View on PubMed
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. Hyrenius-Wittsten A, Roybal KT. Paving New Roads for CARs. Trends Cancer. 2019 10; 5(10):583-592.  View on PubMed
  14. Azimi CS, Tang Q, Roybal KT, Bluestone JA. NextGen cell-based immunotherapies in cancer and other immune disorders. Curr Opin Immunol. 2019 08; 59:79-87.  View on PubMed
  15. 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. Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade. Immunity. 2019 02 19; 50(2):477-492.e8.  View on PubMed
  16. Shalini T. Low-Nam, Jenny JY Lin, Darren B. McAffee, Steven A. Alvarez, Scott D. Hansen, Kole T. Roybal, Jay T. Groves. Beyond the TCR, Antigen Discrimination in T Cells Continues in the LAT:GRB2:SOS Protein Condensate. Biophysical Journal. 2019 Feb 1; 116(3):530a.  View on PubMed
  17. Poornima Ramkumar, Jaime Leong, Meghan Seyler, Stratton J Georgoulis, Axel Hyrenius Wittsten, Priya Choudhry, Kole Roybal, Arun P Wiita, Martin Kampmann. Identifying Factors in Multiple Myeloma Controlling Response to B-Cell Maturation Antigen (BCMA)-Targeted Immunotherapy Using CRISPR-Based Functional Genomics. Blood. 2018 Nov 29; 132(Supplement 1):1926-1926.  View on PubMed
  18. Payal Watchmaker, Joseph Choe, Diego Carrera, Kira Downey, Maryam Shahin, Kole Roybal, Wendell Lim, Hideho Okada. IMMU-57. SEQUENTIAL TWO-RECEPTOR PRIMING CAR SYSTEM TO OVERCOME HETEROGENEOUS ANTIGEN EXPRESSION. Neuro-Oncology. 2018 Nov 5; 20(suppl_6):vi134-vi134.  View on PubMed
  19. Roybal KT. Refining cell therapy. Science. 2018 Mar 09; 359(6380):1112-1113.  View on PubMed
  20. Roybal KT, Lim WA. Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities. Annu Rev Immunol. 2017 04 26; 35:229-253.  View on PubMed

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