Fellowship of the Gutenberg Research College (GRC) (Prof. Dr. José Carlos Alves-Filho)

Current Research

Prof. José Carlos Alves-Filho is a Full Professor in the Department of Pharmacology at Ribeirão Preto Medical School, University of São Paulo (USP), Brazil, and an internationally recognized expert in immunopharmacology and immunoregulation. His research focuses on the cellular and molecular mechanisms that control inflammation and immune responses, with the aim of identifying novel therapeutic targets for inflammatory, infectious, and cancer-related diseases.

Prof. Alves-Filho’s current research is dedicated to understanding the molecular pathways that govern the differentiation, function, and plasticity of Th17 and regulatory T cells (Tregs), as well as dendritic cells. His work addresses fundamental questions in autoimmune inflammation, cancer, and infection, bridging basic immunology with translational approaches to immune modulation. Through advanced experimental disease models, his group has made significant contributions to the field of immune regulation and therapeutic innovation.

Recent studies from his laboratory have provided important insights into the interplay between immune signaling, cellular metabolism, and inflammatory pathology. His group has identified key roles for AIM2 and S100A9 in sustaining psoriasiform inflammation via type 3 immunity and metabolic reprogramming, revealing new potential targets for the treatment of psoriasis and Th17-driven diseases. Additional work has established STING as a checkpoint limiting Th17 pathogenicity and identified PKM2 as a metabolic regulator of STAT3 activation, directly linking immunometabolism to immune effector function.

Ongoing projects in Prof. Alves-Filho’s laboratory further explore the intersection of metabolism and immune regulation. These include studies on the role of PGC1α in connecting mitochondrial function to Treg biology, particularly in cancer, investigations into autoimmune phenotypes arising from Treg-specific loss of DDX41, and analyses of how STING signaling, ERKS kinase activity, and DDX41 broadly shape T cell differentiation and immune homeostasis.

Within the framework of his GRC fellowship at the Institute of Medicalo Microbiology and Hygiene, Prof. Alves-Filho’s research focuses on the role of iron metabolism in the differentiation and function of Tregs. This project aims to elucidate how iron regulation influences Treg biology, immune homeostasis, and immunosuppressive capacity, with direct relevance to autoimmune diseases and cancer. In parallel, the fellowship seeks to establish a dynamic and sustainable collaboration between the University of São Paulo and the University Medical Center of Johannes Gutenberg University Mainz, strengthening immunology research at UM through complementary expertise and shared experimental approaches.

Lab Members

Univ.-Prof. Dr. Jose Carlos Alves-Filho

Univ.-Prof. Dr. Jose Carlos Alves-Filho

GRC Fellow

Selected Publications

  1. Toller-Kawahisa JE, Hiroki CH, Silva CMS, Nascimento DC, Públio GA, Martins TV, Damasceno LEA, Veras FP, Viacava PR, Sukesada FY, Day EA, Zotta A, Ryan TAJ, Cunha TM, Lopes NP, Cunha FQ, O'Neill LAJ, Alves-Filho JC. The metabolic function of pyruvate kinase M2 regulates reactive oxygen species production and microbial killing by neutrophils. Nat Commun. 2023 Jul 17;14(1):4280. doi: 10.1038/s41467-023-40021-6. 
    • This study reveals a crucial role for pyruvate kinase M2 (PKM2) in regulating reactive oxygen species (ROS) production and microbial killing by neutrophils. By linking PKM2’s metabolic function to innate immunity, it highlights a potential therapeutic target to enhance host defense and offers new insights into neutrophil biology and antimicrobial responses.
  2. Nascimento DC, Viacava PR, Ferreira RG, Damaceno MA, Piñeros AR, Melo PH, Donate PB, Toller-Kawahisa JE, Zoppi D, Veras FP, Peres RS, Caetité D, Oliveira AER, Castro ÍMS, Kauffenstein G, Nakaya HI, Borges MC, Zamboni DS, Fonseca DM, Paschoal JAR, Cunha TM, Quesniaux V, Linden J, Cunha FQ, Ryffel B, Alves-Filho JC. Sepsis expands a CD39+ plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity. Immunity. 2021 Sep 14;54(9):2024-2041.e8. doi: 10.1016/j.immuni.2021.08.005.
    • This pivotal study reveals that sepsis drives the expansion of a CD39⁺ plasmablast population, which contributes to long-term immunosuppression by generating adenosine to inhibit macrophage antimicrobial activity. By uncovering this novel immunosuppressive mechanism, this study provides critical insights into the persistence of immune dysfunction following sepsis.
  3. Damasceno LEA, Prado DS, Veras FP, Fonseca MM, Toller-Kawahisa JE, Rosa MH, Públio GA, Martins TV, Ramalho FS, Waisman A, Cunha FQ, Cunha TM, Alves-Filho JC. PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. J Exp Med. 2020 Oct 5;217(10):e20190613. doi: 10.1084/jem.20190613.
    • This landmark study reveals that PKM2, beyond its glycolytic role, acts as a critical regulator of Th17 differentiation and autoimmune inflammation by fine-tuning STAT3 activation. By linking metabolism to immune function, the findings offer new insights into Th17 biology and highlight PKM2 as a promising therapeutic target for autoimmune diseases, reshaping our understanding of metabolic-immune interactions.
  4. Nascimento DC, MeloPH, Pineros AR, Ferreira RG, Colon DF, Donate PB, Castanheira FV, Gozzi A, Czaikoski PG, Niedbala W, Borges MC, Zamboni DS, Liew FY, Cunha FQ, Alves-Filho JC. IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population. Nat Commun. 2017; 8:14919. doi: 10.1038/ncomms14919.
    • This study uncovers a critical role for interleukin-33 (IL-33) in driving long-term immunosuppression following sepsis by expanding the population of Tregs. By identifying IL-33 as a key mediator in this process, the research provides novel insights into the mechanisms underlying post-sepsis immune dysfunction. This work significantly advances the field by highlighting the impact of IL-33 on immune homeostasis after severe infections.
  5. Alves-Filho JC, Sônego F, Souto FO, Freitas A, Verri WA Jr, Basile-Filho A, McKenzie AN, Xu D, Cunha FQ, Liew FY. Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med. 2010; 16(6):708-12. doi: 10.1038/nm.2156
    • This seminal study highlights the protective role of IL-33 in sepsis, demonstrating its ability to enhance neutrophil recruitment to infection sites and improve host survival. This work has significantly influenced the understanding of cytokine-driven immune modulation in sepsis.

Complete list of publications:

https://pubmed.ncbi.nlm.nih.gov/?term=Alves-Filho+JC%5BAuthor%5D&sort=date