{"id":12574,"date":"2026-10-08T14:22:59","date_gmt":"2026-10-08T14:22:59","guid":{"rendered":"https:\/\/gimm.pt\/lab\/laboratorio-daniel-fisch\/"},"modified":"2026-10-14T16:30:30","modified_gmt":"2026-10-14T16:30:30","slug":"laboratorio-daniel-fisch","status":"publish","type":"lab","link":"https:\/\/gimm.pt\/pt-pt\/o-nosso-trabalho\/laboratorios\/laboratorio-daniel-fisch\/","title":{"rendered":"Laborat\u00f3rio Daniel Fisch"},"content":{"rendered":"\n<h3 class=\"wp-block-heading\">Biologia das C\u00e9lulas do Sistema Imunit\u00e1rio Inato<\/h3>\n\n\n\n<p><\/p>\n\n\n\n<p>O nosso grupo investiga como o sistema imunit\u00e1rio inato deteta o perigo, processa informa\u00e7\u00e3o e executa respostas de prote\u00e7\u00e3o. Interessamo-nos pelas &#8220;m\u00e1quinas&#8221; moleculares que permitem \u00e0s c\u00e9lulas detetar infe\u00e7\u00f5es e traduzir esses sinais em inflama\u00e7\u00e3o, defesa antimicrobiana e comunica\u00e7\u00e3o com o sistema imunit\u00e1rio adaptativo. Ao desvendar o funcionamento destes sistemas ao n\u00edvel molecular, pretendemos compreender melhor a imunidade na sa\u00fade e na doen\u00e7a, com implica\u00e7\u00f5es para a infe\u00e7\u00e3o, a autoimunidade e o cancro.<\/p>\n\n\n\n<p>O nosso laborat\u00f3rio utiliza gen\u00e9tica, biologia celular, bioqu\u00edmica e imagiologia quantitativa para descobrir os princ\u00edpios que regem a biologia das c\u00e9lulas do sistema imunit\u00e1rio inato. Ao estudar os detetores, computadores e executores da imunidade como m\u00e1quinas moleculares integradas, procuramos construir um enquadramento mecan\u00edstico sobre como as respostas imunit\u00e1rias s\u00e3o iniciadas, processadas e controladas, e como podem ser manipuladas para fins terap\u00eauticos.<\/p>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<hr class=\"wp-block-separator has-text-color has-alpha-channel-opacity has-background is-style-default\" style=\"background-color:#ff0066;color:#ff0066\"\/>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n<div id=\"\" class=\"wp-block-gimm-accordion\">\n\n\t<div class=\"accordion\" id=\"accordion\">\n\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-areas-de-investigacao\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#areas-de-investigacao\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"areas-de-investigacao\">\n\t\t\t\t\t\t\t<h3>\u00c1reas de Investiga\u00e7\u00e3o<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"areas-de-investigacao\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p><strong>Sinaliza\u00e7\u00e3o pelos Recetores Toll-like \u2013 Detetores e Computadores das Respostas Imunit\u00e1rias<\/strong><br \/>\nA nossa investiga\u00e7\u00e3o centra-se na forma como as c\u00e9lulas do sistema imunit\u00e1rio inato (por exemplo, macr\u00f3fagos) processam sinais de perigo atrav\u00e9s dos recetores Toll-like (TLRs).<br \/>\nEstes recetores funcionam como &#8220;detetores&#8221; de mol\u00e9culas microbianas e associadas a danos, e iniciam programas de sinaliza\u00e7\u00e3o inflamat\u00f3ria que instruem a resposta imunit\u00e1ria mais ampla. Em vez de sinalizarem atrav\u00e9s de vias lineares simples, os TLRs formam grandes plataformas proteicas din\u00e2micas (por exemplo, Myddosomas) que funcionam como &#8220;computadores&#8221; moleculares, integrando inputs e gerando outputs espec\u00edficos.<br \/>\nInvestigamos como estes complexos de sinaliza\u00e7\u00e3o se formam em n\u00edveis end\u00f3genos no interior das c\u00e9lulas, como a sua composi\u00e7\u00e3o e estrutura se alteram ao longo do tempo, e como estas propriedades determinam a qualidade e a magnitude da inflama\u00e7\u00e3o. Estamos tamb\u00e9m a desenvolver ferramentas sint\u00e9ticas que nos permitem construir e controlar estas m\u00e1quinas de sinaliza\u00e7\u00e3o a pedido. Ao dissecar a organiza\u00e7\u00e3o molecular da sinaliza\u00e7\u00e3o pelos TLRs, pretendemos descobrir princ\u00edpios que expliquem como distintas respostas imunit\u00e1rias s\u00e3o processadas e como podem ser seletivamente moduladas.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Prote\u00ednas de Liga\u00e7\u00e3o ao Guanilato (GBPs) \u2013 Guardi\u00e3s da C\u00e9lula a Partir do Interior<\/strong><br \/>\nOutro foco da nossa investiga\u00e7\u00e3o \u00e9 compreender como as c\u00e9lulas detetam e eliminam agentes patog\u00e9nicos intracelulares. Estudamos uma fam\u00edlia de prote\u00ednas induz\u00edveis por interfer\u00e3o conhecidas como prote\u00ednas de liga\u00e7\u00e3o ao guanilato (GBPs), que funcionam na linha da frente da imunidade intr\u00ednseca das c\u00e9lulas. As GBPs podem detetar diretamente invas\u00f5es microbianas, atacar agentes patog\u00e9nicos que entram no citosol e desencadear programas de defesa inflamat\u00f3ria, incluindo formas de morte celular programada para eliminar c\u00e9lulas infetadas. Desta forma, atuam simultaneamente como detetoras e executoras da defesa imunit\u00e1ria.<br \/>\nPara al\u00e9m dos sistemas cl\u00e1ssicos de reconhecimento de padr\u00f5es, as GBPs participam em mecanismos de &#8220;guarda&#8221; que monitorizam a integridade de processos celulares fundamentais e respondem quando os agentes patog\u00e9nicos os perturbam. Esta estrat\u00e9gia confere flexibilidade: em vez de reconhecerem apenas mol\u00e9culas microbianas conservadas, as vias de guarda detetam as consequ\u00eancias da pr\u00f3pria infe\u00e7\u00e3o. O nosso trabalho procura definir como as GBPs s\u00e3o ativadas, como a sua atividade \u00e9 cuidadosamente restringida para evitar danos nos tecidos saud\u00e1veis, e como estes circuitos regulat\u00f3rios moldam a inflama\u00e7\u00e3o. Estamos particularmente interessados em saber se a manipula\u00e7\u00e3o das vias das GBPs poderia potenciar a imunidade antimicrobiana ou a imunoterapia do cancro.<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-publicacoes-selecionadas\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#publicacoes-selecionadas\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"publicacoes-selecionadas\">\n\t\t\t\t\t\t\t<h3>Publica\u00e7\u00f5es Selecionadas<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"publicacoes-selecionadas\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p>Fisch D, Ohri V, Anastasakou E, Wesemann LJ, Choi JH, Lindblad KE, Kagan JC. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42778610\/\" target=\"_blank\" rel=\"noopener\">TRAM promotes Toll-like-receptor-free myddosome signal transduction<\/a>. <strong>Nature<\/strong>. 2026 Sep 23;. doi: 10.1038\/s41586-026-11052-y. [Epub ahead of print] PubMed PMID: 42778610.<\/p>\n<p>Fisch D, Zhang T, Sun H, Ma W, Tan Y, Gygi SP, Higgins DE, Kagan JC. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/38961291\/\" target=\"_blank\" rel=\"noopener\">Molecular definition of the endogenous Toll-like receptor signalling pathways<\/a>. <strong>Nature<\/strong>. 2024 Jul;631(8021):635-644. doi: 10.1038\/s41586-024-07614-7. Epub 2024 Jul 3. PubMed PMID: 38961291; PubMed Central PMCID: PMC12925374.<\/p>\n<p>Fisch D, Pfleiderer MM, Anastasakou E, Mackie GM, Wendt F, Liu X, Clough B, Lara-Reyna S, Encheva V, Snijders AP, Bando H, Yamamoto M, Beggs AD, Mercer J, Shenoy AR, Wollscheid B, Maslowski KM, Galej WP, Frickel EM. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/37797010\/\" target=\"_blank\" rel=\"noopener\">PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection<\/a>. <strong>Science<\/strong>. 2023 Oct 6;382(6666):eadg2253. doi: 10.1126\/science.adg2253. Epub 2023 Oct 6. PubMed PMID: 37797010; PubMed Central PMCID: PMC7615196.<\/p>\n<p>Fisch D, Clough B, Khan R, Healy L, Frickel EM. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34931666\/\" target=\"_blank\" rel=\"noopener\">Toxoplasma-proximal and distal control by GBPs in human macrophages<\/a>. <strong>Pathog Dis.<\/strong> 2022 Jan 7;79(9). doi: 10.1093\/femspd\/ftab058. PubMed PMID: 34931666; PubMed Central PMCID: PMC8752258.<\/p>\n<p>Fisch D, Evans R, Clough B, Byrne SK, Channell WM, Dockterman J, Frickel EM. HRMAn 2.0: <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33930228\/\" target=\"_blank\" rel=\"noopener\">Next-generation artificial intelligence-driven analysis for broad host-pathogen interactions<\/a>. <strong>Cell Microbiol<\/strong>. 2021 Jul;23(7):e13349. doi: 10.1111\/cmi.13349. Epub 2021 May 16. PubMed PMID: 33930228.<\/p>\n<p>Fisch D, Clough B, Domart MC, Encheva V, Bando H, Snijders AP, Collinson LM, Yamamoto M, Shenoy AR, Frickel EM. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32783936\/\" target=\"_blank\" rel=\"noopener\">Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death<\/a>. <strong>Cell Rep.<\/strong> 2020 Aug 11;32(6):108008. doi: 10.1016\/j.celrep.2020.108008. PubMed PMID: 32783936; PubMed Central PMCID: PMC7435695.<\/p>\n<p>Fisch D, Bando H, Clough B, Hornung V, Yamamoto M, Shenoy AR, Frickel EM. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31268602\/\" target=\"_blank\" rel=\"noopener\">Human GBP1 is a microbe-specific gatekeeper of macrophage apoptosis and pyroptosis<\/a>. <strong>EMBO J.<\/strong> 2019 Jul 1;38(13):e100926. doi: 10.15252\/embj.2018100926. Epub 2019 Jun 3. PubMed PMID: 31268602; PubMed Central PMCID: PMC6600649.<\/p>\n<p>Fisch D, Yakimovich A, Clough B, Wright J, Bunyan M, Howell M, Mercer J, Frickel E. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/30744806\/\" target=\"_blank\" rel=\"noopener\">Defining host-pathogen interactions employing an artificial intelligence workflow<\/a>. <strong>Elife<\/strong>. 2019 Feb 12;8. doi: 10.7554\/eLife.40560. PubMed PMID: 30744806; PubMed Central PMCID: PMC6372283.<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-links-uteis\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#links-uteis\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"links-uteis\">\n\t\t\t\t\t\t\t<h3>Links \u00dateis<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"links-uteis\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<ul>\n<li>Bluesky Daniel Fisch <a href=\"https:\/\/bsky.app\/profile\/danielhfisch.bsky.social\" target=\"_blank\" rel=\"noopener\">aqui<\/a><\/li>\n<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\n<\/div>","protected":false},"featured_media":0,"template":"","acf":{"order":"177","header_image":false,"related_research_areas":"","ongoing_projects":"","selected_publications":"","lab_members":"","funding":"","sponsorship":"","extra_information":false,"is_external":false,"location":"Oeiras","subtitle":"Biologia das C\u00e9lulas do Sistema Imunit\u00e1rio Inato","team_leader":[{"ID":12568,"post_author":"1004","post_date":"2026-10-08 14:16:49","post_date_gmt":"2026-10-08 14:16:49","post_content":"","post_title":"Daniel Fisch","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"daniel-fisch","to_ping":"","pinged":"","post_modified":"2026-10-08 14:26:39","post_modified_gmt":"2026-10-08 14:26:39","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/daniel-fisch\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"}],"useful_links":"","awards":"","list_image":{"ID":12572,"id":12572,"title":"Daniel Fish","filename":"Daniel-Fish.png","filesize":181225,"url":"https:\/\/gimm.pt\/wp-content\/uploads\/2026\/10\/Daniel-Fish.png","link":"https:\/\/gimm.pt\/pt-pt\/people\/daniel-fisch\/daniel-fish\/","alt":"","author":"1004","description":"","caption":"","name":"daniel-fish","status":"inherit","uploaded_to":12568,"date":"2026-10-08 14:26:35","modified":"2026-10-08 14:26:35","menu_order":0,"mime_type":"image\/png","type":"image","subtype":"png","icon":"https:\/\/gimm.pt\/wp-includes\/images\/media\/default.png","width":600,"height":600,"sizes":{"thumbnail":"https:\/\/gimm.pt\/wp-content\/uploads\/2026\/10\/Daniel-Fish-150x150.png","thumbnail-width":150,"thumbnail-height":150,"medium":"https:\/\/gimm.pt\/wp-content\/uploads\/2026\/10\/Daniel-Fish-300x300.png","medium-width":300,"medium-height":300,"medium_large":"https:\/\/gimm.pt\/wp-content\/uploads\/2026\/10\/Daniel-Fish.png","medium_large-width":600,"medium_large-height":600,"large":"https:\/\/gimm.pt\/wp-content\/uploads\/2026\/10\/Daniel-Fish.png","large-width":600,"large-height":600,"1536x1536":"https:\/\/gimm.pt\/wp-content\/uploads\/2026\/10\/Daniel-Fish.png","1536x1536-width":600,"1536x1536-height":600,"2048x2048":"https:\/\/gimm.pt\/wp-content\/uploads\/2026\/10\/Daniel-Fish.png","2048x2048-width":600,"2048x2048-height":600}}},"_links":{"self":[{"href":"https:\/\/gimm.pt\/pt-pt\/wp-json\/wp\/v2\/lab\/12574"}],"collection":[{"href":"https:\/\/gimm.pt\/pt-pt\/wp-json\/wp\/v2\/lab"}],"about":[{"href":"https:\/\/gimm.pt\/pt-pt\/wp-json\/wp\/v2\/types\/lab"}],"wp:attachment":[{"href":"https:\/\/gimm.pt\/pt-pt\/wp-json\/wp\/v2\/media?parent=12574"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}