Percorrer por autor "Andaluz, Stephanie"
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- Combined TLR2/TLR4 activation equip non-mucosal dendritic cells to prime Th1 cells with gut tropismPublication . Zúquete, Sara; Ferreira, Mariana; Delgado, Inês L. S.; Gazalle, Paula; Andaluz, Stephanie; Rosa, Maria Teresa; Mendes, Ana Catarina; Santos, Dulce; Nolasco, Sofia; Graça, Luís; Leitão, Alexandre; Basto, Afonso P.Activated CD4+ T cells located at mucosal surfaces orchestrate local effector immune mechanisms. When properly polarized, these cells contribute to block infections at early stages and may be essential to restrain the local growth of mucosal tumors, playing a critical role in host protection. How CD4+ T cells simultaneously integrate gut-homing instructions and Th polarization signals transmitted by TLR-activated dendritic cells (DCs) is unknown. Here, we show that the combined activation through TLR2, which alone does not induce a clear Th polarization, and TLR4, which alone does not imprint mucosal tropism, equip non-mucosal DCs to prime gut-homing CD4+ T cells with reinforced Th1 polarization. These results show that targeting DCs with combined innate stimuli with distinct properties is a rational strategy to program the outcome of T cell polarization and simultaneously control their tissue tropism. Exploring this strategy could enhance the efficacy of vaccines and immune cell therapies.
- Inovação em saúde através da colaboração científica entre o Instituto Politécnico de Lisboa e a Universidade de Macau: impacto e perspetivas futurasPublication . Brito, Miguel; Andaluz, Stephanie; Martins, Rui; Melício, Fernando; Margato, ElmanoA Escola Superior de Saúde de Lisboa - ESSL, do Instituto Politécnico de Lisboa - IPL (Polytechnic University of Lisbon), por intermédio do seu centro de investigação, Health & Technology Research Center - H&TRC, iniciou em 2018 um mecanismo de colaboração com a Universidade de Macau - UM, com o objetivo de formar estudantes de doutoramento e de desenvolver projetos de investigação conjuntos na área da Saúde Humana. A colaboração entre a UM e o IPL foi iniciada em maio de 2018, com uma visita oficial de uma delegação do IPL a Macau, tendo sido assinado um protocolo de cooperação entre as duas instituições, pelo reitor da UM e pelo presidente à data do IPL. O protocolo prevê a promoção de atividades de ensino e investigação em áreas de interesse comum, bem como a colaboração em projetos de investigação. Atualmente, uma estudante portuguesa está a realizar o seu doutoramento na Faculdade de Ciências da Saúde (Faculty of Health Sciences – FHS) da UM, com o apoio duma bolsa da área dos Assuntos Globais desta Universidade. O trabalho decorre no Laboratório de Referência do Estado em Circuitos Integrados em Muito Larga Escala Analógicos e Mistos (State Key Laboratory of Analog and Mixed Signal VLSI - AMSV) e na Faculdade de Ciências e Tecnologia (Faculty of Science and Technology – FST) da UM e no H&TRC, estando em desenvolvimento um dispositivo de diagnóstico portátil para a doença das células falciformes. A colaboração com a FHS da UM estende-se ainda à área da integração de dados multi-ómicos e biologia computacional na análise metagenómica de dados de projetos de investigação do H&TRC, especificamente na análise do microbioma intestinal. Esta colaboração já permitiu publicar vários artigos científicos e está a ser preparada uma patente. Atualmente, as duas instituições estão a candidatar-se a financiamentos, tanto em Portugal como em Macau, com o objetivo de ampliar e reforçar esta colaboração. A colaboração Lisboa-Macau é um exemplo do desenvolvimento de investigação colaborativa de ponta entre instituições de ensino superior.
- Using Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human healthPublication . Andaluz, Stephanie; Zhao, Bojin; Sinha, Siddharth; Lagniton, Philip Naderev Panuringan; Costa, Diogo Alpuim; Ding, Xiaofan; Brito, Miguel; Wang, San MingBackground: Admixture occurs between different ethnic human populations. The global colonization in recent centuries by Europeans led to the most significant admixture in human history. While admixture may enhance genetic diversity for better fitness, it may also impact on human health by transmitting genetic variants for disease susceptibility in the admixture population. The admixture by Portuguese global exploration initiated in the 15th century has reached over 20 million of Portuguese-heritage population worldwide. It provides a valuable model to study the impact of admixture on human health. BRCA1 and BRCA2 (BRCA) are two of the important tumor suppressor genes. The pathogenic variation (PV) in BRCA is well determined to cause a high risk of hereditary breast and ovarian cancer. Tracing the distribution of Portuguese BRCA PV in the Portuguese-heritage population will help to understand the impact of admixture on cancer susceptibility in modern humans. In this study, we analyzed the distribution of the Portuguese-originated BRCA variation in the Brazilian population, which has a high degree of Portuguese heritage. Methods: By comprehensive data mining, standardization, and annotation, we generated a Portuguese-derived BRCA variation dataset and a Brazilian-derived BRCA variation dataset. We compared the two BRCA variation datasets to identify the BRCA variants shared between the two populations. Results: The Portuguese-derived BRCA variation dataset consists of 220 BRCA variants including 78 PVs from 11,482 Portuguese cancer patients, 93 (42.2%) in BRCA1 and 127 (57.7%) in BRCA2. Of the 556 Portuguese BRCA PV carriers carrying the 78 PVs, 331 (59.5%) carried the three Portuguese-BRCA founder PVs of BRCA1 c.2037delinsCC, BRCA1 c.3331_3334del and BRCA2 c.156_157insAlu. The Brazilian-derived BRCA variation dataset consists of 255 BRCA PVs from 7,711 cancer patients, 136 (53.3%) in BRCA1 and 119 (46.6%) in BRCA2. We developed an open database named dbBRCA-Portuguese (https://genemutation.fhs.um.edu.mo/dbbrca-portuguese/) and an open database named dbBRCA-Brazilian (https://genemutation.fhs.um.edu.mo/dbbrca-brazilian) to host the BRCA variation data from Portuguese and Brazilian populations. We compared the BRCA PV datasets between Portuguese and Brazilian populations and identified 29 Portuguese-specific BRCA PVs shared between Portuguese and Brazilian populations, 14 in BRCA1 including the Portuguese founder BRCA1 c.3331_3334del and BRCA1 c.2037delinsCC, and 15 in BRCA2 including the Portuguese founder BRCA2 c.156_157insAlu. Searching the 78 Portuguese BRCA PVs in over 5,000 ancient human genomes identified evolution origin for only 8 PVs in Europeans dated between 37,470 and 3,818 years before the present, confirming the Portuguese-specificity of Portuguese BRCA PVs; comparing the 78 Portuguese BRCA PVs Portuguese, 255 Brazilian BRCA PVs, and 134 African BRCA PVs showed little overlapping, ruling out the possibility that the BRCA PVs shared between Portuguese and Brazilian may also be contributed by African. Conclusion: Our study provides evidence that the admixture in recent human history contributed to cancer susceptibility in modern humans.