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Lacerda, João F.
Lab

Hematology and Transplantation Immunology

The main research focus of our laboratory is the study of immune reconstitution after hematopoietic stem cell transplantation (HSCT) in humans and the development of strategies that modulate immune responses and tolerance post-transplant. Donor immunity emerging post-transplant plays a pivotal role in the protection against pathogens, such as Aspergillus, CMV and EBV, as well as in the development of graft-versus-host disease (GVHD) and graft-versus-leukemia effect.

Our laboratory aims to identify immunological risk factors and the mechanisms by which these complications emerge post-transplant. We are particularly interested in developing strategies that may be translated into the clinical setting, such as the use of pathogen-specific T cells, donor regulatory T cells for GVHD and disease-specific T cells, with the aim of improving patient survival. We also maintain research lines investigating the pathogenesis of hematologic malignancies.

  • Research Areas

    • Immune reconstitution after hematopoietic stem cell transplantation (HSCT)
    • Homeostasis of regulatory T cells (Treg) in patients submitted to HSCT
    • Adoptive transfer of donor Treg in patients with chronic graft-versus-host disease (GvHD) – ongoing clinical trial
    • Recruitment and expansion of antigen-specific Treg cells
    • Pathogen-specific T cell therapy following HSCT
    • Genetic susceptibility to invasive fungal infections
  • Research Team

    • Ongoing Research Projects

      • 2015/2019 J. F. Lacerda PI and COORDINATOR of the Consortium. EC HORIZON 2020 Collaborative Project, Research and Innovation Action. TREGeneration. Grant Agreement no. 643776. Repair of tissue and organ damage in refractory chronic graft versus host disease after hematopoietic stem cell transplantation by the infusion of purified allogeneic donor regulatory T lymphocytes
      • 2013/2016 J. F. Lacerda PI - FLFCT/Harvard Medical School Portugal; HMSP-ICT/0001/2011 - Induction of immune tolerance after allogeneic stem cell transplantation
    • Prizes

    • Selected Publications

      • The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells. Chorny A, Casas-Recasens S, Sintes J, Shan M, Polentarutti N, García-Escudero R, Walland A, Yeiser J, Cassis L, Carrillo J, Puga I, Cunha C, Bastos H, Rodrigues F, Lacerda JF, Morais A, Dieguez-Gonzalez R, Heeger P, Salvatori G, Carvalho A, Garcia-Sastre A, Blander JM, Mantovani A, Garlanda C, Cerutti A​. - J Exp Med. (in press) 2016
      • Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD. Alho AC, Kim HT, Chammas MJ, Reynolds CG, Matos TR, Forcade E, Whangbo J, Nikiforow S, Cutler CS, Koreth J, Ho VT, Armand P, Antin JH, Alyea EP, Lacerda JF, Soiffer RJ, Ritz J. - Blood. 2016, PMID: 26670634
      • Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels. Gomes AM, Soares MV, Ribeiro P, Caldas J, Póvoa V, Martins LR, Melão A, Serra-Caetano A, de Sousa AB, Lacerda JF*, Barata JT*. (*joint last authors) - Haematologica. 2014, PMID: 24561792
      • Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O, Grube M, Löffler J, Maertens JA, Bell AS, Inforzato A, Barbati E, Almeida B, Santos e Sousa P, Barbui A, Potenza L, Caira M, Rodrigues F, Salvatori G, Pagano L, Luppi M, Mantovani A, Velardi A, Romani L, Carvalho A. - N Engl J Med. 2014, PMID: 24476432
      • Long-term immune reconstitution of naive and memory t cell pools after haploidentical hematopoietic stem cell transplantation. Azevedo RI, Soares MV, Albuquerque AS, Tendeiro R, Soares RS, Martins M, Ligeiro D, Victorino RM, Lacerda JF, Sousa AE. - Biol Blood Marrow Transplant. 2013, PMID: 23396243
      • The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma. Carvalho A, Cunha C, Almeida AJ, Osório NS, Saraiva M, Teixeira-Coelho M, Pedreiro S, Torrado E, Domingues N, Gomes-Alves AG, Marques A, Lacerda JF, da Silva MG, Gomes M, Pinto AC, Torres F, Rendeiro P, Tavares P, Di Ianni M, Medeiros R, Heutink P, Bracci PM, Conde L, Ludovico P, Pedrosa J, Maciel P, Pitzurra L, Aversa F, Marques H, Paiva A, Skibola CF, Romani L, Castro AG, Rodrigues F. - Genes Immun. 2012, PMID: 21866115
      • Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood gammadelta T cells. Gomes AQ, Correia DV, Grosso AR, Lança T, Ferreira C, Lacerda JF, Barata JT, Silva MG, Silva-Santos B. - Haematologica. 2010, PMID: 20220060
      • A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P, Nagler A, Di Bartolomeo P, Lacerda JF, Lupo Stanghellini MT, Polge E, Frassoni F, Martelli MF, Rocha V; Acute Leukemia Working Party (ALWP) of European Blood and Marrow Transplant (EBMT) Group. - Blood. 2008, PMID: 18606875
      • Unrelated stem cell transplantation after a reduced intensity conditioning regimen containing high-dose thymoglobulin leads to controllable graft-versus-host disease. Lacerda JF, Martins C, Lourenço F, Carmo JA, Juncal C, Oliveira JJ, Lacerda JM. - Biol Blood Marrow Transplant. 2007, PMID: 17382257

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