CARE
Boosting Clinical Research for the Benefit of Society, is a Teaming for Excellence project, in collaboration with the Vall d’Hebron Institut de Recerca (VHIR), in Barcelona. Pioneering in Portugal, with a core mission-driven, human-centred and data-driven research and innovation model, based on the involvement of all stakeholders – citizens, patients, health professionals, researchers, business people, industry, health authorities and government – in interdisciplinary, cross-sectoral collaborations to solve health challenges.
CARE is developing and promoting excellence in clinical and translational research, profoundly transforming how clinical and translational research is conceptualized, planned and implemented to deliver effective solutions to the most pressing health needs.
Striving for a Better Future
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For the healthcare ecosystem to function optimally, citizens and patients need timely access to innovative preventative, diagnostic and tailored healthcare solutions (e.g. for earlier detection or improved symptom management to reduce mortality and/or to increase healthy life expectancy). It is also essential that citizens and patients are more actively involved throughout the R&I process to ensure continued relevance, achieve user-centricity and promote literacy. To better understand the continuum between bench and bedside, healthcare professionals need advanced training in research approaches and researchers need exposure to the realities of healthcare.
Researchers in academia and industry need comprehensive access to state-of-the-art clinical and translational research infrastructures to develop their work. With a novel advancement in hand, innovators and entrepreneurs then need expert and continuous support to mature, protect and scale-up their innovations to become next-generation solutions, attractive for investment.
To ensure these solutions are tested effectively, clinical trials activity, in Portugal specifically, needs systemic reforms to remove key bottlenecks. To complete the cycle, health authorities and policymakers need access to the latest R&I results to inform policy and prioritize investment of public funds. Throughout this pipeline, all stakeholders need to be able to effectively communicate across sectors of the health ecosystem to build trust, co-create initiatives and source continued support.
CARE is a dedicated research and innovation (R&I) initiative designed to significantly reduce the time between the emergence of innovative healthcare solutions and their practical application for the benefit of human health. CARE will establish a pioneering Center of Excellence in human-centered clinical and translational research in Portugal, through the joint effort of the GIMM Foundation and the Valld’Hebron Institute of Research (VHIR).
At the heart of CARE resides a mission-oriented, people-centred and data-driven R&I model bringing together stakeholders from different sectors-citizens, patients, researchers, medical professionals, engineers, healthcare providers, industry leaders, entrepreneurs, policymakers, government authorities and philanthropists-through an independent platform for informed dialogue. Stakeholders will be invited to engage in multidisciplinary collaborations to solve health challenges via
- selected disease-specific missions and implementation of flagship R&I projects
- the setup of a next generation biobank
- the creation of a path of excellence in clinical research and trials, profoundly transforming design, planning and execution, to provide effective and timely solutions for the most pressing healthcare needs.
An articulated set of coordination and support actions will leverage the reach of new technologies and digital data to accelerate the path to innovation with comprehensive collaborative efforts across the healthcare value chain.
Translational Research Lines
Advanced Breast Cancer Translational Laboratory
We aim to reduce the incidence and mortality of Metastatic Breast Cancer (MBC), with the primary goal of increasing early (stage I) diagnosis from 30% to 70% within the next 10 years.
In 2020, in Portugal, almost 7,000 women were diagnosed with and 1,800 died of breast cancer (BC). The BC subtypes differ in key genetic alterations, therapeutic strategies and clinical prognosis, which are largely conditioned by the metastatic behavior of the cancer. In the absence of identified risk factors, a 50-year-old woman is screened by mammogram every two years (until her 70th birthday) through the National Health System. This screening program allows for only about 30% of the women diagnosed to be identified at stage I. Almost 40% of women are diagnosed at stage II, and 20% and 7% are diagnosed at stage III and metastatic IV, respectively. The detection of cancers at later stages has a significant impact on the efficacy of cancer treatments and affects the progression free survival (and evolution towards metastatic stage) and/or the overall survival. The first aim of this mission is to improve the detection of early-stage BC to achieve 70% of women diagnosed within the next 10 years. At the same time, treatment of BC, in particular metastatic disease, raises many challenges, due to resistance to available therapies. Thus, a second goal is to develop and implement custom-made tests that will allow the identification of biomarkers and phenotypic features predisposing to metastatic behavior and therapy resistance. This mission is in complete alignment with Europe’s Beating Cancer Plan (1), with the EU recommending extending breast cancer screening from women aged 50 to 69 to include women between 45 and 74 years of age (2).
To address the two challenges of Mission 2, we propose to design, develop and implement BC comprehensive genomic profiling from blood and fecal samples as a novel, highly sensitive and precise companion test for early detection of BC, for therapy response prediction at the diagnosis stage, and for monitoring therapeutic response throughout the treatment course. To overcome limitations of deep profiling of circulating tumor DNA, due to the difficulty of detection in the early stages of cancer, we propose to take advantage of the emerging relationships between human cancers and the gut microbiome. In fact, growing evidence suggests that circulating microbial DNA (cmDNA) may have predictive value to discriminate between healthy individuals and patients with subtypes of BC. By combining the identification of detailed BC-driving gene copy number and mutations with the detection of specific microbial DNA, our original approach will have increased specificity, innovative character and clinical relevance.
In collaboration with public/private hospitals in the Lisbon area, a prospective breast cancer longitudinal collection of tumor specimens (at diagnosis and post-treatment), adjacent normal tissue, blood and feces, with detailed patient clinical history will be established. We will determine the tumor mutational landscape and local immune response, and the tumor and fecal microbiomes. We will uncover novel associations between selective tumor mutations, specific bacteria species and immune/stromal responses in TME, using dimensionality reduction combined with machine learning methods. This information will be crossed with spatial distribution of tumor cells, phenotype of the TME constituents in situ and the patient clinical data. This will facilitate the revelation of biomarkers predicting treatment response. The therapeutic relevance of these biomarkers will be demonstrated by the detection of circulating tumor DNA and circulating and gut mDNA to create easy- to-use breast cancer comprehensive genomic profiling blood and fecal tests. The most robust biomarkers will be interrogated for their potential role in mechanism(s) of therapy resistance/sensitivity and of cancer progression/ metastasis, allowing identification of novel treatment options preventing the emergence or progression of advanced MBCs.
(2) Questions and answers: A new EU approach to cancer screening
Brain Cancer Dynamics & Therapy Translational Laboratory
One of the most intriguing and fatal characteristic of brain tumors is dissemination. This phenomenon can occur through dissemination of cancer cells from distant organs to the brain (brain metastases) or within the central nervous system (CNS) from primary brain tumors (medulloblastoma and ependymoma). The relevance to study brain metastatic disease relies in the absence of effective therapies, leading to severe disability and poor patient survival.
Therefore, our lab aims at understanding the dynamics of cancer cells and the mechanisms leading to CNS dissemination, the identification of biomarkers for early cancer detection using liquid biopsies and high-throughput genomics, and the development of novel treatment protocols using patient-derived models of brain metastatic disease.
We are a highly multidisciplinary and collaborative group combining the expertise of experimental biologists and clinicians from diverse disciplines in Neuro-Oncology, in the campus and beyond. Our translational projects take advantage of a large Brain Tumor Collection at the Biobanco-iMM CAML harbouring biological samples (tumor tissue, blood, plasma and cerebrospinal fluid) with detailed clinical annotation from pediatric and adult patients. In our lab we use cellular and molecular biology techniques, advanced microscopy, computational biology, and in vivo models of brain tumors. We are particularly interested in developing ex vivo organotypic models and patient-derived xenografts of brain tumors.
Check the page of the Centro de Investigação de Tumores Cerebrais, for more information and to donate for our research.
Microbiome in Health & Disease Translational Laboratory
The Microbiome in Health and Disease Translational Laboratory is an interdisciplinary and highly collaborative team of clinical microbiologists, computational biologists, nutritionists, immunologists, and gastroenterologists.
Our lab is dedicated to leveraging the potential of the microbiome to revolutionize the field of colorectal cancer (CRC) research. Our mission is to develop innovative diagnostic tools and microbiome-based biotherapeutics to intercept, prevent, and treat CRC.
Our research focuses on three key areas:
Biomarker Discovery: We aim to identify and validate novel gut microbiome biomarkers for risk assessment and early CRC diagnosis using precision microbiome profiling and machine learning technology. By analyzing the gut microbiota in individuals at different stages of CRC, we aim to enhance screening methods and enable early intervention.
Host-Microbiome Interactions: We study the role of microbial metabolites in shaping host immune responses in CRC. Through metabolomic profiling and culturomics, we aim to uncover the specific microbial metabolites linked to distinct immune responses in CRC. This knowledge will deepen our understanding of the microbiome-immune system crosstalk and facilitate the development of novel biotherapeutics.
Microbiome-based therapeutics: Another important focus of our lab is the development of microbiota consortia comprising commensal immune-stimulating bacteria. By harnessing the power of these beneficial microbes, we aim to modulate the host immune system in a favourable manner, potentially mitigating the risk of CRC development or aiding in treatment strategies. This research avenue holds promise for the development of novel probiotics or microbial-based therapies that can be tailored to specific individuals or subgroups at risk.
Through an ambitious and multidisciplinary approach that combines cutting-edge techniques in genomics, metabolomics, and immunology, our lab strives to unravel the complex interplay between the microbiome and CRC. By elucidating the underlying mechanisms, we aim to translate our findings into tangible clinical applications that will have a significant impact on cancer prevention, diagnosis, and treatment.
Mission Lab
Research and Innovation | Personalized Medicine Solutions
The Mission Lab is a dedicated scientific support team, in conjunction with a specific structure facilitating design, testing, scale-up and deployment capacities from core biomedical research at IMM. This structure was initially set up during the COVID-19 pandemic as the Molecular Diagnostics Centre, with a professional, agile clinical testing operation allowing iMM to take a leading role in testing deployment at the national level.
The Mission Lab was then reshaped to support new Research & Innovation in the implementation phase, helping to deliver new preventive, diagnostic and personalized medicine solutions.
CARE - Biobank
CARE Biobank is integrated in the Academic Medical Center of Lisbon (CAML), which brings together on the same campus a medical school (Faculdade de Medicina da Universidade de Lisboa – FMUL), an university hospital (Centro Hospitalar Lisboa Norte – CHLN, Hospital de Santa Maria – HSM), and GIMM’s Lisbon site.
Biobanks are strategic tools for the development of medicine and translational research. The biobank includes biological samples (from surgery, biopsies, blood samples, …) which are voluntarily donated with permission for preservation and future use in biomedical research.
All samples are accompanied by clinical information, a crucial factor for subsequent research. The biobank is approved by the Institutional Ethics Committee and by the National Commission for Data Protection.
It allows the study of the pathogenesis of multiple diseases with enormous impact on human health (such as neurological diseases, rheumatic disorders and cancer), improving the identification of new prognostic and diagnostic tests and new therapeutic targets. Our vision is that the biobank will be a contribution for promoting health and well-being of society, but will also have the potential to act as a catalyst for new opportunities for cooperation between national and international researchers, institutions and pharmaceutical industry.
Scientific Commission – Evaluates proposals and authorizes sample use.
Members: João Eurico da Fonseca, Cristina Ferreira, Alexandre Mendonça, Dulce Brito, Joana Caetano-Lopes, Leonor Correia Guedes, Luís Costa, Ruth Geraldes, Sandra Casimiro
Technical Commission – Ensures the legal and technical framework for proper functioning.
Members: Filipa Nunes
The biobank is available to establish agreements with researchers to provide specific services.
These services include:
- Nucleic Acid extraction (DNA and RNA) from whole blood, tissue and cells
- Peripheral Blood Mononuclear Cells (PBMC) isolation
- Primary cell culture of human skin fibroblasts
- Sample processing according to good laboratory practice (GLP) and Standard Operating Procedures