Inflammation and Neurodegeneration

The main interest of our Laboratory is to assess the contribution of peripheral immune cells to the pathogenesis of neurodegenerative, cardiovascular, genetic and infectious diseases.

The activation of innate and adaptive immune responses is a self-defensive reaction, triggered to restore homeostasis and to eliminate harmful stimuli that compromise the integrity of the affected tissues. In the last decade, immunity and inflammation were shown to play important roles in a variety of disorders, including neurodegenerative, cardiovascular, genetic and infectious diseases. Hence, the main interest of our Laboratory is to assess the contribution of peripheral immune cells to the pathogenesis of aforementioned pathologies. Given the cross-talk between inflammation and iron metabolism, our focus is also to understand the pathophysiological consequences resulted from the associated disruption of heme and iron homeostasis.

Graphical Abstract

Projects

EOS – The Excellence of Science (40007512). Funds provided by the Belgian National Fund for Scientific Research (FNRS) for the research project entitled: “Cell Death Regulation and Role in Infection and Inflammatory Diseases”. From 2022 to 2026.
Collaborative Investigation Price – Santander Totta/NOVA University of Lisbon. Funds provided by the Santander Totta Bank for the research project entitled: “Stress-induced neuroinflammation: mechanisms and implications for decision-making and performance”. From 2018 to 2021.
EOS – The Excellence of Science (30826052). Funds provided by the Belgian National Fund for Scientific Research (FNRS) for the research project entitled: “MOlecular mechanisms of cellular DEath and Life decisions in Inflammation, Degeneration and Infection”. From 2018 to 2022.
Investigator Programme (IF/01495/2015). Funds provided by the Fundação pela Ciência e Tecnologia (FCT) for the research project entitled: “Immunity and inflammation in Parkinson’s disease”. From 2016 to 2021.
Programas de Atividades Conjuntas (PAC) (03/SAICT/2015). Funds provided by the Fundação pela Ciência e Tecnologia (FCT) for the research project entitled: “NEw Targets in DIAstolic heart failure: from coMOrbidities to persoNalizeD medicine (NETDIAMOND)”. From 2017 to 2020.
Immunology Grant Fall 2015. Funds provided by the Pharmaceutical and Biotechnology Company BD Bioscience for the research project entitled: “Immune regulation of bone morphogenic pathways in Axial Spondyloarthritis. From 2015 to 2017.
iNOVA4Health-Multi/04462. Funds provided by the Programme in Translational Medicine iNOVA4Health for the research project entitled: “The importance of Haptoglobin/Hemopexin axis in the pathogenesis of Axial Spondyloarthritis”. From 2015 to 2018.

Publications

Lima IS & Pêgo AC, Barros JT, Prada AR, Gozzelino R. Cell death-osis of dopaminergic neurons and the role of iron in Parkinson’s disease. Antioxid Redox Signal. 2021 Jan 15.
Ferreira A, Neves P, Gozzelino R. Multilevel impacts of iron in the brain: cross talk between neurophysiological mechanisms, cognition and social behavior. Pharmaceuticals. 2019 Aug 29;12(3). pii: E126.
Ramos S, Carlos AR, Sundaram B, Jeney V, Ribeiro A, Gozzelino R, et al. Renal Control of Disease Tolerance To Malaria. Proc Natl Acad Sci U S A. 2019 Mar 19;116(12):5681-5686.
Agoro R, Benmerzoug S, Rose S, Bouyer M, Gozzelino R, et al. Iron-rich diet decreases mycobacterial burden and correlates with hepcidin upregulation, lower pro-inflammatory mediators and higher T cell recruitment in a model of M. bovis BCG infection. The Journal of Infectious Diseases, 2017, Oct 17;216(7):907-918.
Martins AC, Lima IS, Almeida JI, Kapitão AS and Gozzelino R. Iron metabolism and the inflammatory response. IUBMB Life 2017, Jun;69(6):442-450.
Gozzelino R* and Arosio P*. Iron homeostasis in health and disease. Int J Mol Sci. 2016 Jan 20;17(1)(*equal contrib.).
Arosio P, Carmona F, Gozzelino R, Maccarinelli F, Poli M. The importance of eukaryotic ferritins in iron handling and cytoprotection. Biochemical Journal. Biochem J. 2015 Nov 15;472(1):1-15.
Yilmaz B, Portugal S, Tran TM, Gozzelino R, Ramos S, et al. Gut microbiota elicits a protective immune response against malaria transmission. Cell. 2014 Dec 4;159(6):1277-89.
Soares MP, Gozzelino R and Weis S. Tissue damage control in disease tolerance. Trends Immunol. 2014 Aug 30.
Gozzelino R* and Soares MP*. Coupling heme and iron metabolism via Ferritin H chain. Antioxid Redox Signal. 2014 Apr 10(*equal contrib.).
Figueiredo N, Chora A, Raquel H, Pejanovic N, Pereira P, Hartleben B, Neves-Costa A, Moita C, Pedroso D, Pinto A, Marques S, Faridi H, Costa P, Gozzelino R, et al. Anthracyclines induce DNA damage response-mediated protection against severe sepsis. Immunity. 2013 Nov 14;39(5):874-84.
Marques-Fernandez F, Planells-Ferrer L, Gozzelino R, et al. TNFα induces PC12 cells survival through the FLIP-L-dependent activation of the MAPK/ERK pathway. Cell Death Dis. 2013 Feb 14;4:e493.
Casanelles E*, Gozzelino R*, Marques-Fernandes F, et al. Bcl-xL, but not Mcl-1, Bcl-2 or Bcl-w, controls TNF-triggered apoptosis regardless of NF-kB activation in HeLa cells. Biochim Biophys Acta. 2013 Jan 28(*equal contrib.).
Gozzelino R, Andrade BB, Larsen R, et al. Metabolic adaptation to tissue iron overload confers tolerance to malaria. Cell Host Microbe. 2012 Nov 15;12(5):693-704.
Larsen R, Gouveia Z, Soares MP, Gozzelino R. Heme Cytotoxicity And The Pathogenesis of Immune Mediated Inflammatory Diseases. Front Pharmacol. 2012;3:77.
Larsen R, Gozzelino R, Jeney V, et al. Targeting free heme to suppress the pathogenesis of severe sepsis. Sci Transl Med. 2010 Sep 29;2(51):51ra71.
Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1. Annual Rev Pharmacol Toxicol. 2010;50:323-54.
Seixas E*, Gozzelino R*, Chora A, Ferreira A, et al. Heme oxygenase-1 affords protection against noncerebral forms of severe malaria. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15837-42.(*equal contrib.).
Gozzelino R, Sole C, Llecha N, Segura MF, et al. Bcl-xL regulates TNF-alpha-mediated cell death independently of NF-kB, FLIP and IAPs. Cell Res. 2008 Oct;18(10):1020-36.
Segura MF, Sole C, Pascual M, Moubarak RS, Perez-Garcia MJ, Gozzelino R, et al. The long form of Fas apoptotic inhibitory molecule is expressed specifically in neurons and protects them against death receptor-triggered apoptosis. J Neurosci 2007 Oct 17;27(42):11228-41.
Sole C, Dolcet X, Segura MF, Gutierrez H, Diaz-Meco MT, Gozzelino R, et al. The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-kB signaling. J Cell Biol. 2004 Nov 8;167(3):479-92.

Prizes and Awards

2019: ESNM – TANDEM award 2019 (attributed to Ms. Ana Catarina Guilherme Pêgo, a PhD student in my laboratory).
2018: (a) Collaborative Investigation Price - Santander-Totta, (b) Best Poster Presentation Award (19th biennial meeting for the Society for Free Radical Research International, SFRRI).
2017: Tribute by the Cape Verde’s Embassy in Lisbon for scientific merit, dedication and contribution as Woman In Science.
2016: (a) Springer Book Voucher Award for Best Presentation (Understanding the Molecular Brain in Health and Disease Symposium) (b) Best Poster Presentation Award (International Heme Oxygenase Meeting).
2015: (a) Elsevier Award for Outstanding Contribution as member of the Editorial Board (b) Frontiers Award for Outstanding Contribution as member of the Editorial Board (c) Gunshin Levy Award (International BioIron Society) (d) Pfizer Price.
2013: Best podium presentation (International BioIron Society)