John Warrington

Program: Computational and Systems Biology

Current advisor: Nathan Singh, MD, MS

Undergraduate university: University of South Carolina

Research summary
Chimeric antigen receptor (CAR) T cell therapy has revolutionized treatment of B cell leukemia and lymphomas. However, over half of the patients receiving CAR T cell therapy ultimately have their disease progress. This failure is largely due to imprecise CAR signaling.

In Nathan Singh’s lab, I am working on engineering the signaling domain of CARs to prevent T cell dysfunction and improve tumor clearance of CAR T cells. Currently, I am generating experimental wet lab data to be used in downstream deep learning applications for CAR engineering. Ultimately, I hope to develop a CAR capable of more robust T cell activation leading to increased cytotoxicity, proliferation, and persistence than current CARs.

Graduate publications
Chang JF, Landmann JH, Chang TC, Selli ME, Tenzin Y, Warrington JM, Ritchey J, Hsu YS, Slade M, Gupta DK, DiPersio JF, Holehouse AS, Singh. 2024 Rational protein engineering to enhance MHC-independent T cell receptors. Cancer Discov, ():Online ahead of print.

Selli ME, Landmann JH, Terekhova M, Lattin J, Heard A, Hsu YS, Chang TC, Chang J, Warrington J, Ha H, Kingston N, Hogg G, Slade M, Berrien-Elliott MM, Foster M, Kersting-Schadek S, Gruszczynska A, DeNardo D, Fehniger TA, Artyomov M, Singh N. 2023 Costimulatory domains direct distinct fates of CAR-driven T-cell dysfunction. Blood, 141(26):3153-3165.

Heard A, Landmann JH, Hansen AR, Papadopolou A, Hsu YS, Selli ME, Warrington JM, Lattin J, Chang J, Ha H, Haug-Kroeper M, Doray B, Gill S, Ruella M, Hayer KE, Weitzman MD, Green AM, Fluhrer R, Singh N. 2022 Antigen glycosylation regulates efficacy of CAR T cells targeting CD19. Nat Commun, 13():3367.

Heard A, Chang J, Warrington JM, Singh N. 2021 Advances in CAR design. Best Pract Res Clin Haematol, 34(3):101304.

 

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