{"id":1317,"date":"2024-07-31T14:30:21","date_gmt":"2024-07-31T14:30:21","guid":{"rendered":"https:\/\/gimm.pt\/our-work\/laboratories\/laboratorio-ribot-silva-santos\/"},"modified":"2025-09-23T09:56:14","modified_gmt":"2025-09-23T09:56:14","slug":"laboratorio-ribot-silva-santos","status":"publish","type":"lab","link":"https:\/\/gimm.pt\/pt-pt\/o-nosso-trabalho\/laboratorios\/laboratorio-ribot-silva-santos\/","title":{"rendered":"Laborat\u00f3rio Ribot &amp; Silva-Santos"},"content":{"rendered":"\n<h3 class=\"wp-block-heading\">Neuro-Imunologia e Imuno-Oncologia<\/h3>\n\n<p><\/p>\n\n<p>A investiga\u00e7\u00e3o desenvolvida no laborat\u00f3rio conjunto Julie Ribot &amp; Bruno Silva-Santos, com base na Imunologia Celular e Molecular, persegue quest\u00f5es fundamentais relacionadas com a biologia dos gl\u00f3bulos brancos (leuc\u00f3citos). Dois programas de investiga\u00e7\u00e3o principais s\u00e3o geridos por dois l\u00edderes de grupo independentes e cooperativos:<\/p>\n\n<p>A <strong>Neuro-Imunologia<\/strong>, dirigida por Julie Ribot, que visa dissecar os cruzamentos neuro-imunes, por exemplo, considerando as contribui\u00e7\u00f5es fisiopatol\u00f3gicas da IL-17 para al\u00e9m da vigil\u00e2ncia imunit\u00e1ria; e <strong>a Imuno-Oncologia<\/strong>, dirigida por Bruno Silva-Santos, que investiga as interac\u00e7\u00f5es celulares e moleculares no microambiente tumoral, com enfoque nas c\u00e9lulas T gama-delta (\u03b3\u03b4).<\/p>\n\n<h5 class=\"wp-block-heading\">Neuro-Imunologia<\/h5>\n\n<p>Atualmente, assistimos ao aparecimento de um conjunto de provas que documentam novas fun\u00e7\u00f5es do sistema imunit\u00e1rio, interagindo com outros sistemas complexos de \u00f3rg\u00e3os para manter a homeostase dos tecidos, independentemente do desafio dos agentes patog\u00e9nicos. Avan\u00e7os recentes permitiram descobrir que o sistema imunit\u00e1rio tamb\u00e9m actua como um re\u00f3stato tecidular que detecta continuamente perturba\u00e7\u00f5es homeost\u00e1ticas e contribui para a fisiologia est\u00e1vel dos \u00f3rg\u00e3os.<\/p>\n\n<p>Recentemente, identific\u00e1mos uma popula\u00e7\u00e3o de c\u00e9lulas T \u03b3\u03b4 que se infiltram nos linf\u00e1ticos dentro da dura-m\u00e1ter das meninges cerebrais. Demonstr\u00e1mos que este subgrupo \u00e9 uma fonte importante de IL-17, que promove a mem\u00f3ria de curto prazo atrav\u00e9s do aumento da plasticidade sin\u00e1ptica neuronal no hipocampo. Por outro lado, relat\u00e1mos ainda um aumento significativo de c\u00e9lulas men\u00edngeas produtoras de IL-17, que desencadeia o in\u00edcio do decl\u00ednio cognitivo num modelo de rato da doen\u00e7a de Alzheimer. Assim, postulamos um papel duplo para a IL-17: pr\u00f3-cognitivo em estado estacion\u00e1rio e anti-cognitivo no contexto da neurodegenera\u00e7\u00e3o, e destacamos que uma regula\u00e7\u00e3o rigorosa dos n\u00edveis de IL-17 men\u00edngea \u00e9 fundamental para manter a integridade do c\u00e9rebro. Estas considera\u00e7\u00f5es levaram-nos a levantar quest\u00f5es neurocient\u00edficas sob um \u00e2ngulo imunol\u00f3gico inovador:<\/p>\n\n<ul>\n<li><strong>Como \u00e9 que os n\u00edveis de IL-17 s\u00e3o ajustados de forma a garantir fun\u00e7\u00f5es cognitivas \u00f3ptimas?<\/strong><\/li>\n<\/ul>\n\n<p>Estamos a avaliar o impacto das pistas ambientais utilizando diversas abordagens, como a manipula\u00e7\u00e3o farmacol\u00f3gica do sistema, a abla\u00e7\u00e3o cir\u00fargica e modelos gen\u00e9ticos espec\u00edficos de ratinhos. Como leitura experimental, utilizamos sobretudo a citometria de fluxo para analisar a paisagem imunit\u00e1ria dos tecidos (com enfoque nos produtores de IL-17), bem como a sequencia\u00e7\u00e3o de ARN para a carateriza\u00e7\u00e3o pioneira do perfil transcricional de subgrupos com uma resolu\u00e7\u00e3o de c\u00e9lula \u00fanica.<\/p>\n\n<ul>\n<li><strong>Qual \u00e9 o impacto da regula\u00e7\u00e3o da IL-17 na fisiopatologia dos tecidos?<\/strong><\/li>\n<\/ul>\n\n<p>Estamos a desvendar novos processos neurofisiol\u00f3gicos sob a regula\u00e7\u00e3o da IL-17 no sistema nervoso central e perif\u00e9rico, nomeadamente focando a aprendizagem e a mem\u00f3ria, a ansiedade, o sono e a regenera\u00e7\u00e3o nervosa. Para tal, utilizamos modelos gen\u00e9ticos de ratinhos, microscopia, ensaios comportamentais e eletrofisiologia.<\/p>\n\n<h5 class=\"wp-block-heading\">Imuno-Oncologia<\/h5>\n\n<p>Na nossa linha de investiga\u00e7\u00e3o em Imuno-Oncologia, que tem sido financiada pela Funda\u00e7\u00e3o &#8220;la Caixa&#8221;, pela Organiza\u00e7\u00e3o Europeia de Biologia Molecular e pela Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, estudamos os cruzamentos celulares e moleculares no microambiente tumoral (TME), tentando potenciar os mecanismos anti-tumorais (baseados na citotoxicidade e na secre\u00e7\u00e3o de interfer\u00e3o-gama) em detrimento dos efeitos pr\u00f3-tumorais (ligados \u00e0 inflama\u00e7\u00e3o e \u00e0 angiog\u00e9nese). Al\u00e9m disso, traduzimos o conhecimento seminal que produzimos sobre as c\u00e9lulas T gama-delta (\u03b3\u03b4) para o desenvolvimento de uma nova metodologia para a terapia celular adotiva do cancro &#8211; c\u00e9lulas T Delta One (DOT) &#8211; no \u00e2mbito de uma empresa spin-off, a Lymphact SA, adquirida em 2018 pela GammaDelta Therapeutics (Londres, Reino Unido), e que faz agora parte do portf\u00f3lio de imunoterapia da Takeda. Na nossa equipa, continuamos a estudar as c\u00e9lulas DOT, a sua regula\u00e7\u00e3o funcional e os seus mecanismos moleculares de reconhecimento das c\u00e9lulas tumorais, em colabora\u00e7\u00e3o com a Takeda.<\/p>\n\n<p>Tamb\u00e9m conduzimos uma linha de investiga\u00e7\u00e3o mais fundamental em Imuno-Biologia, que tem sido financiada por Starting e Consolidator Grants do Conselho Europeu de Investiga\u00e7\u00e3o (ERC), onde nos concentramos no desenvolvimento t\u00edmico e na diferencia\u00e7\u00e3o funcional das c\u00e9lulas T gama-delta (\u03b3\u03b4). O nosso objetivo \u00e9 identificar novos mecanismos moleculares envolvidos na sua gera\u00e7\u00e3o t\u00edmica e nas respostas imunit\u00e1rias perif\u00e9ricas a infec\u00e7\u00f5es (como a mal\u00e1ria) e ao cancro.<\/p>\n","protected":false},"featured_media":0,"template":"","acf":{"header_image":false,"ongoing_projects":"","selected_publications":"","useful_links":"","awards":"","funding":"","sponsorship":"","extra_information":false,"location":"Lisboa","subtitle":"Neuro-Imunologia e Imuno-Oncologia","team_leader":"","order":"310","is_external":false,"related_research_areas":[1499,1504],"lab_members":[{"ID":8380,"post_author":"1004","post_date":"2025-05-27 13:42:46","post_date_gmt":"2025-05-27 13:42:46","post_content":"","post_title":"Bruno Silva-Santos","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"bruno-miguel-de-carvalho-e-silva-santos","to_ping":"","pinged":"","post_modified":"2026-03-13 10:12:11","post_modified_gmt":"2026-03-13 10:12:11","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/bruno-miguel-de-carvalho-e-silva-santos\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":8383,"post_author":"1004","post_date":"2025-05-27 13:42:46","post_date_gmt":"2025-05-27 13:42:46","post_content":"","post_title":"Julie Ribot","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"julie-cecile-caroline-ribot","to_ping":"","pinged":"","post_modified":"2026-03-13 10:12:16","post_modified_gmt":"2026-03-13 10:12:16","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/julie-cecile-caroline-ribot\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":8143,"post_author":"1002","post_date":"2025-05-27 13:43:19","post_date_gmt":"2025-05-27 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