Nuno R. dos Santos is a Principal Researcher at i3S-Instituto de Investigação e Inovação em Saúde in Porto. He obtained his PhD at the Radboud University (Nijmegen, the Netherlands), mentored by Ad Geurts van Kessel, on the functional characterization of SS18 and SSX synovial sarcoma proteins. He then followed postdoctoral training mentored by Jacques Ghysdael at the Institut Curie (Orsay, France) where he investigated the molecular mechanisms underlying T-cell leukemia development. During that period, he gained extensive experience in the development and analysis of mouse models of lymphoid leukemia. His work led to i) generation of a mouse model of B-cell lymphoma (Leukemia, 2006), ii) identification of the pre-T cell receptor as a contributing factor in T-cell leukemogenesis (Blood, 2007), iii) demonstration that calcineurin phosphatase inactivation impairs T-cell leukemia (Nature Medicine, 2007), and iv) the demonstration that expression of the RelB NF-kappaB transcription factor in microenvironmental cells plays a tumor-promoting role (PLoS One, 2008). These discoveries were foundational for the establishment in 2008 of his own research group at the Center for Biomedical Research (CBMR) of the University of Algarve (Faro, Portugal). Here, while training MSc and PhD students, he continued investigating microenvironmental and molecular mechanisms underlying T-cell leukemia. Among other findings, his group found that lymphotoxin signaling in the thymic microenvironment (Br J Haematol, 2015) and FoxN1 transcription factor expression in thymic epithelial cells (Carcinogenesis, 2018) contributed to T-cell leukemia development. Moreover, he and collaborators identified an unsuspected tumor suppressive function for the T-cell receptor in mouse and human T-cell leukemia, resulting in a high impact publication (Cancer Discovery, 2016). In 2016, he moved and integrated i3S-Instituto de Investigação e Inovação em Saúde in Porto, where he coordinates a team pursuing projects in leukemia and lymphoma molecular biology. His team has found that low-affinity TCR stimulation can promote T-cell leukemia (J. Leukoc. Biol., 2025) and that the CDKN2A tumor suppressor gene acts as a gatekeeper for the malignant transformation of T cell precursors lacking pre-TCR (Exp. Hematol., 2022). His team has also been investigating the role of the cell surface P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoma. They found that PSGL-1 overexpression in a T-cell lymphoma cell line promoted tumor growth and dissemination (Transl. Oncol., 2021). They then found that this protein plays a complex role in lymphoma because its targeting with a specific antibody led to apoptosis of human T and B lymphoma cell lines (Hematol. Oncol., 2024). Additional studies identified PSGL-1 as a novel immune checkpoint in B-cell lymphoma and demonstrated that targeting it with antibodies enhanced T-cell activation, reduced tumor burden, and improved chimeric antigen receptor (CAR) T-cell efficacy (Leukemia, 2025), offering a promising new immunotherapeutic approach for lymphomas resistant to traditional checkpoint inhibitors. He has published 33 articles in peer-reviewed journals (>70% as first or last co-author), trained 13 Master, 6 PhD students and 2 postdoc fellows, received 10 awards and/or honors, obtained competitive funding from FCT, La Caixa Foundation, APCL, Fundação AstraZeneca, LPCC and Gilead Sciences (8 projects), presented in international meetings, organized 2 national and 1 European conference, reviewed many grant applications and manuscripts. Performed outreach activities, such as lab visits, student lectures, media interviews and a TEDx talk. >> Lab website: http://sites.google.com/site/nunordossantos/