{"id":1327,"date":"2024-07-31T14:30:22","date_gmt":"2024-07-31T14:30:22","guid":{"rendered":"https:\/\/gimm.pt\/our-work\/laboratories\/laboratorio-miguel-soares\/"},"modified":"2024-08-02T14:11:28","modified_gmt":"2024-08-02T14:11:28","slug":"laboratorio-miguel-soares","status":"publish","type":"lab","link":"https:\/\/gimm.pt\/pt-pt\/o-nosso-trabalho\/laboratorios\/laboratorio-miguel-soares\/","title":{"rendered":"Laborat\u00f3rio Miguel Soares"},"content":{"rendered":"\n<h3 class=\"wp-block-heading\">Inflama\u00e7\u00e3o<\/h3>\n\n<p><\/p>\n\n<p>A imunidade evoluiu nos organismos multicelulares para limitar o potencial impacto negativo resultante da exposi\u00e7\u00e3o cont\u00ednua a micr\u00f3bios. Os componentes inatos e adaptativos do sistema imunit\u00e1rio s\u00e3o dotados da capacidade de detetar e de visar os microrganismos patog\u00e9nicos para os conter, destruir ou expulsar, como forma de preservar a homeostasia e a aptid\u00e3o do organismo. A resist\u00eancia \u00e0 infe\u00e7\u00e3o refere-se ao resultado destas fun\u00e7\u00f5es imunit\u00e1rias.<\/p>\n\n<p>Os organismos multicelulares tamb\u00e9m desenvolveram outra estrat\u00e9gia de defesa que preserva a homeostase e a aptid\u00e3o do organismo sem exercer um impacto negativo direto sobre os microrganismos. Esta estrat\u00e9gia de defesa, designada por toler\u00e2ncia \u00e0 doen\u00e7a, baseia-se em respostas evolutivamente conservadas ao stress e aos danos que limitam a extens\u00e3o da disfun\u00e7\u00e3o metab\u00f3lica e dos danos impostos aos tecidos do par\u00eanquima, quer diretamente por microrganismos patog\u00e9nicos, quer indiretamente por mecanismos de resist\u00eancia imunit\u00e1rios.<\/p>\n\n<p>O objetivo geral do <strong>Laborat\u00f3rio de Inflama\u00e7\u00e3o<\/strong> \u00e9 identificar e caraterizar estas respostas ao stress e aos danos que conferem o controlo dos danos nos tecidos e estabelecem a toler\u00e2ncia \u00e0 infe\u00e7\u00e3o.<\/p>\n\n<p>A hip\u00f3tese central testada \u00e9 que existe uma intera\u00e7\u00e3o funcional entre os mecanismos de resist\u00eancia imunit\u00e1ria e as respostas ao stress e aos danos que actuam nos tecidos do par\u00eanquima, para limitar, contrariar e reparar os efeitos patog\u00e9nicos da infe\u00e7\u00e3o.<\/p>\n\n<p>A compreens\u00e3o dos mecanismos celulares e moleculares que regem esta rede de interac\u00e7\u00f5es e respostas dever\u00e1 ser transformadora na nossa compreens\u00e3o das interac\u00e7\u00f5es hospedeiro-micr\u00f3bio, com impacto direto no tratamento de doen\u00e7as infecciosas.<br\/><br\/><strong>Contribui\u00e7\u00f5es cient\u00edficas originais:<\/strong><\/p>\n\n<ol>\n<li>Identificou que o metabolismo renal do ferro-heme no rim \u00e9 essencial para contrariar a patog\u00e9nese da mal\u00e1ria grave (Proc. Natl. Acad. Sci. USA. 2019).<\/li>\n\n\n\n<li>Identificou uma rede de regula\u00e7\u00e3o cruzada entre o metabolismo do ferro e da glicose que \u00e9 essencial para estabelecer a toler\u00e2ncia da doen\u00e7a \u00e0 s\u00e9psis (Cell 2017).<\/li>\n\n\n\n<li>Descobriu uma intera\u00e7\u00e3o simbi\u00f3tica atrav\u00e9s da qual os componentes bacterianos da microbiota intestinal provocam uma resposta de anticorpos que contraria a transmiss\u00e3o da mal\u00e1ria (Cell, 2014).<\/li>\n\n\n\n<li>Descobriu que a regula\u00e7\u00e3o do metabolismo do ferro e estabelece a toler\u00e2ncia a infec\u00e7\u00f5es sist\u00e9micas (Cell Host &amp; Microbe, 2012).<\/li>\n\n\n\n<li>Descobriu um mecanismo molecular central atrav\u00e9s do qual a hemoglobina falciforme estabelece a toler\u00e2ncia da doen\u00e7a \u00e0 mal\u00e1ria (Cell, 2011).<\/li>\n\n\n\n<li>Revelou que a enzima responsiva ao stress heme oxigenase-1 apoia a sobreviv\u00eancia de um hospedeiro infetado independentemente da sua carga patog\u00e9nica, fornecendo a primeira base mecanicista para o estabelecimento da toler\u00e2ncia \u00e0 mal\u00e1ria (Nature Medicine, 2007 e Proc. Natl. Acad. Sci. USA. 2009) e \u00e0 s\u00e9psis (Science TM, 2010; Science, 2012).<\/li>\n\n\n\n<li>Descobriu que o gasotransmissor mon\u00f3xido de carbono (CO), gerado atrav\u00e9s do catabolismo do heme pela heme oxigenase-1, actua terapeuticamente numa s\u00e9rie de condi\u00e7\u00f5es inflamat\u00f3rias imunomediadas, incluindo a rejei\u00e7\u00e3o de \u00f3rg\u00e3os transplantados (J. Immunology, 2001, Nature Medicine, 2003), arteriosclerose (Nature Medicine, 2003), les\u00e3o de isquemia e reperfus\u00e3o (FASEB Journal. 2004), neuroinflama\u00e7\u00e3o autoimune (J. Clinical Investigation 2007) e mal\u00e1ria grave (Nature Medicine, 2007).<\/li>\n<\/ol>\n\n<p>O nosso atual corpo de trabalho foi desencadeado, em grande medida, pela demonstra\u00e7\u00e3o original, com o falecido <a href=\"https:\/\/www.nytimes.com\/2011\/08\/18\/us\/18bach.html\" rel=\"noreferrer noopener\" target=\"_blank\">Fritz H. Bach<\/a> na Harvard Medical School, de que o mon\u00f3xido de carbono (CO), um gasotransmissor, actua de forma citoprotectora (J. Exp. Med., 2001) e imunoreguladora (Nature Medicine, 2000), fornecendo uma base mecanicista para a forma como os \u00f3rg\u00e3os transplantados evitam a sua pr\u00f3pria rejei\u00e7\u00e3o (Nature Medicine, 1998).<\/p>\n","protected":false},"featured_media":0,"template":"","acf":{"header_image":false,"ongoing_projects":"","selected_publications":"","useful_links":"","awards":"","funding":null,"sponsorship":null,"extra_information":false,"location":"Oeiras","subtitle":"Inflama\u00e7\u00e3o","team_leader":[],"order":"350","related_research_areas":[1499,1502],"lab_members":[{"ID":8311,"post_author":"1004","post_date":"2025-05-27 13:42:55","post_date_gmt":"2025-05-27 13:42:55","post_content":"","post_title":"Miguel Soares","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"miguel-che-parreira-soares","to_ping":"","pinged":"","post_modified":"2026-03-13 10:02:59","post_modified_gmt":"2026-03-13 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