For this edition of the contest, a total of nine groundbreaking biomedical and health projects spearheaded by research institutions in Portugal were selected. Alongside CF, GIMM, and i3S, awards were also granted to projects from the Instituto de Tecnologia Química e Biológica António Xavier da Universidade Nova de Lisboa (ITQB NOVA), Instituto de Investigação em Ciências da Vida e da Saúde (ICVS) and Instituto de Biomedicina (iBiMED). These nine selected projects will receive more than €7.6 million in support. This funding underscores the commitment of the “la Caixa” Foundation to champion projects of unparalleled excellence that stand to significantly benefit public health.
Listed below is more information about the five awardees from CF, GIMM, and i3S, and their projects.
Ana Luísa Correia, CF
Spatiotemporal dynamics of organ-specific microenvironments in breast cancer metastasis
Mortality from cancer is almost exclusively a result of tumour metastasis to distant sites. Many patients with breast cancer experience a long delay (years to decades) between diagnosis of the primary tumour and detection of metastases in distant organs. This pause in progression results from disseminated tumour cells that enter dormancy until they adapt to the new microenvironment and awaken as metastases. Since metastatic relapse is still largely incurable, understanding how the microenvironment triggers disseminated tumour cells to shift from dormancy to metastatic outgrowth is a critical challenge in cancer research today.
DynaMet will map the landscape of the microenvironments that support or oppose metastasis in the two most common and deadliest sites of breast cancer metastasis (liver and bone), in both mouse models and humans. Combining the unique expertise of the laboratories led by Ana Luísa Correia at CF and Neta Erez at Tel Aviv University in studying the biology of metastasis, we will identify where and when the microenvironment within each organ changes to facilitate metastatic outgrowth. “Our multidisciplinary approach goes beyond the conventional study of individual cell types or factors in isolation and will provide a global mechanistic view of how the specific physiology, architecture, and resident cells of each organ steer metastatic efficiency”, explains Ana Luísa. “By revealing a novel role for anatomical organisation in controlling dormancy and the emergence of metastases, DynaMet will transform our understanding of the rate-limiting step of metastasis and how we approach it therapeutically”.
Ana Luísa asserts, “Support from the La Caixa Foundation will pave the way for understanding and intercepting metastasis formation, inspiring a novel class of microenvironment-based therapies tailored to address the specific characteristics of metastasis in each organ. Our approach has the potential to catalyse a step change in cancer treatment by refocusing efforts from treating metastases to reliably preventing their establishment altogether”.
Bio: Ana Luísa Correia received her B.Sc. in Applied Biology from the University of Minho, Portugal. As a GABBA student, she ventured to California in the USA to pursue her PhD studies on the role of the microenvironment in breast cell invasion. As a European Molecular Biology Organization (EMBO) Postdoctoral Fellow at the Friedrich Miescher Institute for Biomedical Research and the University of Basel in Switzerland, she pioneered research on tissue-specific mechanisms controlling breast cancer metastasis. Ana Luísa now leads the Cancer Dormancy & Immunity Lab at CF. Her group strives to understand what makes a tissue favourable or not to metastasis and to leverage this biology into therapeutic interventions that reliably prevent the emergence of metastases in cancer patients. Ana Luísa has received several international awards (2021 Metastasis Research Prize, 2022 Pfizer Oncology, AACR 2022 NextGen Stars), is an EMBO Young Investigator, and serves as an active member of the American, European, and Portuguese associations for Cancer Research (AACR, EACR, and ASPIC) and the Metastasis Research Society.
Bruno Silva-Santos, GIMM
Novel regulators of gamma-delta T cell subset differentiation and activation in infection
Infectious diseases like malaria or tuberculosis are still a major burden worldwide, as the available vaccines are incapable of fully preventing infection and eradicating disease. New developments require a better understanding of the immune system and how it may organise protective responses to such microbes. For many years, Bruno Silva-Santos has worked on a specific type of immune cell, the gamma delta T cells, which proliferate vigorously in response to malaria or tuberculosis. Even though these cells are associated with these diseases, for now, there are no means to manipulate their response for the benefit of the host.
In this project, now funded by the “la Caixa” Foundation, the team will identify molecules in gamma delta T cells that may become new therapeutic targets. They will focus on molecules involved in crucial processes in these cells, such as their activation and differentiation, by studying, for example, the mechanisms that allow gamma delta T cells to respond to infection through the production of special immune hormones, called cytokines. By developing this project they aim to discover new molecular strategies to mobilise the desired type of gamma delta T cell response in different pathologies that can open new and more effective strategies for controlling these challenging infections.
"This project will allow us to investigate a poorly understood immune cell subset, gamma-delta T cells, in the context of infectious diseases, aiming to boost their protective roles while reducing potentially harmful inflammatory effects. For my group, which is mostly dedicated to cancer immunotherapy, this grant will allow us to have part of the team focused on infectious diseases and thus enhance the global impact of our research”, says Bruno Silva-Santos.
Bio: Bruno Silva-Santos is a Principal Investigator at the Gulbenkian Institute for Molecular Medicine, and Full Professor and Director of Immuno-Oncology at the Faculty of Medicine, University of Lisbon. He also currently serves as the President of the Portuguese Society for Immunology (SPI). He completed his PhD in Immunology at University College London in 2002, with research conducted at Cancer Research UK (The London Research Institute), and later trained as a postdoctoral fellow at King’s College London before founding his own group in Lisbon in 2006. His research, primarily focused on gamma-delta T cells, has been funded by the European Research Council (2010, 2015) and the "la Caixa" Foundation (2020, 2024), and he has published over 120 papers in leading international peer-reviewed journals. In 2019, he was elected a Member of the European Molecular Biology Organization (EMBO) in recognition of his scientific contributions. His patented work on “Delta One T (DOT) cells” led to the founding of the cancer immunotherapy start-up Lymphact. Lymphact’s proprietary technology was acquired by Takeda Pharmaceutical in 2022 and is currently undergoing clinical testing in the USA (NCT05886491).
Luísa Figueiredo, GIMM
Decoding trypanosome interactions with the host vasculature
Certain parasites, immune cells or tumour cancer cells travel through the blood circulation and cross blood vessels to invade organs. The parasite Trypanosoma brucei, which causes fatal diseases in Africa, crosses blood vessels, and invades various organs such as adipose tissue and the brain. This allows parasites to hide inside organs, which hampers diagnosis and worsens outcomes. In this project, the researchers aim to find parasite genes that facilitate the crossing of blood vessels, understand how the blood vessels change during infection, and elucidate the step-by-step process of parasite vascular crossing.
By collaborating with the laboratory led by Cláudio Franco in Católica Biomedical Research Centre, Portugal, which is specialised in vascular biology, the team will uncover how parasites exploit blood vessels. This knowledge may offer new treatment strategies for the diseases caused by the Trypanosome parasite, but also other pathologies that might use similar mechanisms such as cancer metastasis and inflammation.
“This grant will fund a truly interdisciplinary project bringing together the fields of parasitology and vascular biology. Understanding the role of vasculature in trypanosomiasis will allow us to better understand how this disease can be chronic for several years and escape standard diagnostic tests”, says Luísa Figueiredo.
“The “la Caixa” grant will support the productive synergy between Luísa Figueiredo’s lab and mine, at the interface between parasitology and vascular biology. This generous funding will help us uncover new mechanisms of blood vessel crossing, which could aid in treating trypanosomiasis and cancer metastasis”, adds Cláudio Franco, collaborator in this project.
Bio: Luísa Figueiredo is a Principal Investigator at the Gulbenkian Institute for Molecular Medicine and a Guest Associate Professor at the Medical School, University of Lisbon. Her research focuses on African trypanosomes, parasites responsible for sleeping sickness in humans and nagana in cattle. Figueiredo's lab has earned international acclaim for uncovering that these parasites can adapt functionally to specific tissues, revealing a previously unknown aspect of their life cycle. She has published over 51 peer-reviewed articles (over 2,400 citations, H-index 25), addressing topics such as epigenetic regulation in Trypanosoma brucei, tissue tropism, circadian metabolic control, and transcriptional regulation of differentiation. A former European Molecular Biology Organization (EMBO) Installation Grantee, Luísa Figueiredo was recently elected an EMBO Member. Her research has been supported by grants from the Howard Hughes Medical Institute (2012), the European Research Council (2017), and the "la Caixa" Foundation (2020, 2023). She has also contributed significantly to the establishment of the institutional working group on Equity, Diversity, and Inclusion.
Marc Veldhoen, GIMM
A new strategy to modulate T-lymphocyte action and prevent hyperreactive immune responses
Infectious and inflammatory diseases, whose prevalence is increasing globally, are one of the leading causes of mortality worldwide. Many of these pathologies are related to the activity of T-lymphocytes, a type of white blood cell responsible for orchestrating the immune attack against pathogens. Sometimes, these defensive cells overreact, which can lead to the development of serious conditions such as fibrosis, chronic obstructive pulmonary disease or asthma.
Broad-spectrum immunosuppressive drugs, which target general processes, are often used to avoid these complications, but these drugs have significant side effects and increase the risk of infection. This makes it necessary to develop new therapeutic options that can selectively inhibit the activity of T-lymphocytes.
Marc Veldhoen’s team already discovered a factor that is crucial for the activation of these defensive cells. In the project now funded by the “la Caixa” Foundation, in collaboration with Silvia Almeida from Co-Lab AccelBio, experts in drug discovery, the researchers will explore this factor as a new therapeutic target to identify drugs that can modulate the T-lymphocyte response without affecting the rest of the protective immune function. This project could provide tools to avoid the common side effects when treating infectious and inflammatory diseases.
“I am very grateful to have been awarded another prestigious grant from la Caixa Health Research for our proposal, which reflects “la Caixa” Foundation's critical support and commitment to pioneering and innovative research. This grant will enable us to advance a very promising project on controlling inappropriate T cell responses in immune-mediated inflammatory diseases”, says Marc Veldhoen.
Bio: Marc Veldhoen is a Principal Investigator at the Gulbenkian Institute for Molecular Medicine and, since 2018, a Professor of Basic Immunology at the Faculty of Medicine, University of Lisbon. His research focuses on T cell biology, especially tissue-resident T cells. He holds an MSc in Medical Biology from the Faculty of Medicine, University of Utrecht, and a PhD in Immunology from the National Institute for Medical Research (NIMR), London, UK. He completed his postdoctoral training at NIMR, where he studied T helper cell differentiation. In 2010, he established his own research group in Cambridge, UK, focusing on mucosal T cells, with support from an ERC consolidator grant and an EMBO Young Investigator award. In 2016, he accepted the ERA Chair position at the Instituto de Medicina Molecular, Lisbon, where he continued his work on T cell biology, especially in tissues, supported by a “la Caixa” Health Research Grant (2019).
Tiago Beites, i3S
Exploiting host free fatty acids to sterilize Mycobacterium tuberculosis infections
Tuberculosis (TB) is currently the deadliest infectious disease, claiming the lives of over 1 million people every year. Although effective, TB chemotherapy is long, involves multiple drugs and is associated with severe adverse effects, making patient compliance very challenging. Incomplete treatment leads to avoidable deaths and sets the ground for the emergence of resistant strains. The problem is even more complicated in low- and middle-income countries, where antibiotics supply chains sometimes fail. The development of strategies that can shorten treatment duration is thus of paramount importance in the efforts to eradicate TB.
Infection foci of Mycobacterium tuberculosis, the bacterium that causes the disease, are notorious for lipid accumulation. This sets the selective pressure for M. tuberculosis to use lipids as a source of carbon and energy. However, some lipids, namely free fatty acids, are also potent antimicrobials. The researchers have previously discovered mechanisms used by M. tuberculosis to safely consume free fatty acids. In this project, the researchers will provide a comprehensive understanding of this fundamental adaptation to the host and identify promising bona fide drug targets that can be exploited for drug development.
“Mycobacterium tuberculosis has been co-evolving with humans for millennia. It is a very successful pathogen because it evolved to trick our immune system in very creative ways. In this project, we aim at fighting back by tricking M. tuberculosis into getting intoxicated with its own diet. This is a strategy that can validate new drug targets, and ultimately increase our armamentarium in the efforts to eradicate TB”, explains Tiago Beites.
Bio: Tiago Beites completed his undergraduate studies in Biology in the Faculty of Sciences, University of Porto in 2007, and his PhD degree in the same university in 2013. In 2015, he joined the laboratory of Professor Sabine Ehrt at Weill Cornell Medicine (New York, US) as a postdoctoral associate to work on fundamental biology of the human pathogen Mycobacterium tuberculosis. From 2020 until 2023, he held junior faculty positions at Weill Cornell Medicine (New York, US), first as Instructor and later as Assistant Professor of Research. In July 2023, he joined i3S - University of Porto as an Assistant Researcher. Currently, Tiago Beites coordinates a team under the umbrella concept of pathogen target biology, with a current focus on M. tuberculosis.
About the CaixaResearch Health Call 2024:
The “la Caixa” Foundation has allocated a total of €25.7 million for 29 projects from Portugal & Spain. This funding will support scientific studies over the next three years.
For this edition of the contest, 580 proposals were put forward, reflecting the contest's mission to spotlight and foster projects that embody scientific excellence, vast potential, and profound societal impact, spanning basic to clinical, translational, and pioneering research.
The CaixaResearch Contest collaborates closely with the Foundation for Science and Technology (FCT), the Portuguese public agency that supports science, technology and innovation, in all scientific domains. In this edition, FCT is funding 3 out of the 9 selected Portuguese projects, contributing almost €2.5 million.
The financial aid provided to the chosen projects is categorised into two brackets:
1. Up to €500,000 over a span of three years for projects presented by a singular research entity.
2. Up to €1,000,000 over three years for projects presented by consortia, comprising 2 to 5 research entities.
Since its inception in 2018, the “La Caixa” Foundation has dedicated €145.7 million to 200 innovative research projects with significant societal impact. Of these, 63 were spearheaded by research groups from Portugal. Currently, this is the most important philanthropic call for research in biomedicine and health in Portugal and Spain. A panel of international experts meticulously evaluates the proposals for each edition, conducting interviews with shortlisted candidates and selecting the most promising projects.
Text by Hedi Young, Science Writer and Content Developer of the Champalimaud Foundation's Communication, Events and Outreach team, in partbnership with GIMM and i3S Communication teams.
