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What We Do

The Sharpe laboratory investigates T cell costimulatory pathways and their immunoregulatory functions. We focus on the roles of these pathways in regulating pathogenic and protective immune responses needed for the induction and maintenance of T cell tolerance and the prevention of autoimmunity, as well as effective antimicrobial and antitumor immunity.

We are also involved in studies aimed at translating the fundamental understanding of T cell costimulation into new therapies for autoimmune diseases, chronic viral infections, and cancer. Manipulation of T cell costimulatory pathways is of great therapeutic interest as it may provide a means to enhance immune responses to promote anti-microbial and tumor immunity, or to terminate immune responses to control autoimmune diseases and achieve tolerance for organ transplantation.

Recent Publications

2025

LaFleur M, Milling L, Prathima P, Li V, Lemmen A, Streeter I, Heisig PKS, Derosia N, Riffo E, Xu H, et al. A STUB1–CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity. Nature Immunology. 2025;26. doi:10.1038/s41590-025-02231-6
LaFleur M, Milling L, Prathima P, Li V, Lemmen A, Streeter I, Heisig PKS, Derosia N, Riffo E, Xu H, et al. A STUB1–CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity. Nature Immunology. 2025;26. doi:10.1038/s41590-025-02231-6

2024

Milling L, Markson S, Tjokrosurjo Q, Derosia N, Streeter I, Hickok G, Lemmen A, Nguyen T, Prathima P, Fithian W, et al. Framework for in vivo T cell screens. J Exp Med. 2024;221(4). doi:10.1084/jem.20230699
Milling L, Markson S, Tjokrosurjo Q, Derosia N, Streeter I, Hickok G, Lemmen A, Nguyen T, Prathima P, Fithian W, et al. Framework for in vivo T cell screens. J Exp Med. 2024;221(4). doi:10.1084/jem.20230699
Burke K, Chaudhri A, Freeman G, Sharpe A. The B7:CD28 family and friends: Unraveling coinhibitory interactions. Immunity. 2024;57(2):223–244. doi:10.1016/j.immuni.2024.01.013
Burke K, Chaudhri A, Freeman G, Sharpe A. The B7:CD28 family and friends: Unraveling coinhibitory interactions. Immunity. 2024;57(2):223–244. doi:10.1016/j.immuni.2024.01.013
Cohen J, Gouirand V, Macon C, Lowe M, Boothby I, Moreau J, Gratz I, Stoecklinger A, Weaver C, Sharpe A, et al. Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche. Sci Immunol. 2024;9(91):eadh0152. doi:10.1126/sciimmunol.adh0152
Cohen J, Gouirand V, Macon C, Lowe M, Boothby I, Moreau J, Gratz I, Stoecklinger A, Weaver C, Sharpe A, et al. Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche. Sci Immunol. 2024;9(91):eadh0152. doi:10.1126/sciimmunol.adh0152
LaFleur M, Lemmen A, Streeter I, Nguyen T, Milling L, Derosia N, Hoffman Z, Gillis J, Tjokrosurjo Q, Markson S, et al. X-CHIME enables combinatorial, inducible, lineage-specific and sequential knockout of genes in the immune system. Nat Immunol. 2024;25(1):178–188. doi:10.1038/s41590-023-01689-6
LaFleur M, Lemmen A, Streeter I, Nguyen T, Milling L, Derosia N, Hoffman Z, Gillis J, Tjokrosurjo Q, Markson S, et al. X-CHIME enables combinatorial, inducible, lineage-specific and sequential knockout of genes in the immune system. Nat Immunol. 2024;25(1):178–188. doi:10.1038/s41590-023-01689-6