# Home ![rsz_1arlene_tc_room_01.jpg](/sites/g/files/omnuum4061/files/styles/hwp_28_10__1920x685/public/sharpe/files/rsz_1arlene_tc_room_01.jpg?itok=DeKP0Hd9) ## 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 Download 5 citations download- [BibTeX](/bibcite/export?pager_style=no_pager&number_of_items=5&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=bibtex) - [EndNote X3 XML](/bibcite/export?pager_style=no_pager&number_of_items=5&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=endnote8) - [EndNote 7 XML](/bibcite/export?pager_style=no_pager&number_of_items=5&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=endnote7) - [Endnote tagged](/bibcite/export?pager_style=no_pager&number_of_items=5&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=tagged) - [Marc](/bibcite/export?pager_style=no_pager&number_of_items=5&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=marc) - [PubMedId](/bibcite/export?pager_style=no_pager&number_of_items=5&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=pubmed_id) - [RIS](/bibcite/export?pager_style=no_pager&number_of_items=5&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=ris) ### 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](https://www.nature.com/articles/s41590-025-02231-6). 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](https://www.nature.com/articles/s41590-025-02231-6). Nature Immunology. 2025;26. doi:10.1038/s41590-025-02231-6 - add\_circle do\_not\_disturb\_on Abstract In vivo CRISPR screens in CD8+ T cells have previously uncovered targets for cancer immunotherapy; however, a minority of the genome has been individually annotated, suggesting that additional regulators remain to be discovered. Here we assessed 899 genes... ### 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](/publications/framework-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](/publications/framework-vivo-t-cell-screens). J Exp Med. 2024;221(4). doi:10.1084/jem.20230699 - add\_circle do\_not\_disturb\_on Abstract In vivo T cell screens are a powerful tool for elucidating complex mechanisms of immunity, yet there is a lack of consensus on the screen design parameters required for robust in vivo screens: gene library size, cell transfer quantity, and number of mice... Burke K, Chaudhri A, Freeman G, Sharpe A. [The B7:CD28 family and friends: Unraveling coinhibitory interactions](/publications/b7cd28-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](/publications/b7cd28-family-and-friends-unraveling-coinhibitory-interactions). Immunity. 2024;57(2):223–244. doi:10.1016/j.immuni.2024.01.013 - add\_circle do\_not\_disturb\_on Abstract Immune responses must be tightly regulated to ensure both optimal protective immunity and tolerance. Costimulatory pathways within the B7:CD28 family provide essential signals for optimal T cell activation and clonal expansion. They provide crucial... 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](/publications/regulatory-t-cells-skin-mediate-immune-privilege-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](/publications/regulatory-t-cells-skin-mediate-immune-privilege-hair-follicle-stem-cell-niche). Sci Immunol. 2024;9(91):eadh0152. doi:10.1126/sciimmunol.adh0152 - add\_circle do\_not\_disturb\_on Abstract Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is maintained in these tissues. We developed a technique to restrict genetic recombination to... 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](/publications/x-chime-enables-combinatorial-inducible-lineage-specific-and-sequential-knockout). 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](/publications/x-chime-enables-combinatorial-inducible-lineage-specific-and-sequential-knockout). Nat Immunol. 2024;25(1):178–188. doi:10.1038/s41590-023-01689-6 - add\_circle do\_not\_disturb\_on Abstract Annotation of immunologic gene function in vivo typically requires the generation of knockout mice, which is time consuming and low throughput. We previously developed CHimeric IMmune Editing (CHIME), a CRISPR-Cas9 bone marrow delivery system for... [ More arrow\_circle\_right ](/publications)