20 November 2025
Four Principal Investigators from two institutions – the Champalimaud Foundation (CF), and the Gulbenkian Institute for Molecular Medicine (GIMM) – have secured funding from the CaixaResearch Health Call 2025 to advance research into how the brain controls impulsive behaviour, new nanotechnology- and cell-based cancer immunotherapies, and the mechanisms that maintain genome stability and influence ageing.
These four selected projects will receive more than €1.75 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 four awardees from CF and GIMM, and their projects.
This research explores how the brain balances short- and long-term information, a process crucial for making adaptive decisions. When this balance fails, it can lead to problems such as impulsivity, addiction, or poor decision-making, which are common features of disorders like attention deficit hyperactivity disorder (ADHD) and substance abuse.
Using mice as a model, the team aims to understand how different brain circuits process information across multiple timescales to guide actions. In particular, they will study the role of dopamine, a key brain chemical involved in learning and decision-making, across several regions of the brain. By combining advanced recording techniques with tools like optogenetics – a method that uses light to control the activity of specific neurons – the researchers will both measure and manipulate brain activity to see how these circuits shape behaviour.
“Our brains are constantly weighing the immediate versus the longer term consequences of our choices”, says Joe Paton, Principal Investigator of the Learning Lab at the Champalimaud Foundation. “We want to understand how this balance is achieved in the brain’s decision-making circuits – and what happens when this process goes awry, as in impulsivity or addiction. By uncovering these mechanisms, we hope to not only deepen our understanding of brain function but also inform new approaches to treat disorders of self-control and decision-making”.
After completing his PhD at Columbia University, Joe Paton established the Learning Lab at the Champalimaud Foundation, where he now serves as both Principal Investigator and Director of Neuroscience. His research has significantly advanced understanding of the neural mechanisms underlying value learning, temporal processing, dopamine function, and the hierarchical organisation of basal ganglia circuits that control behaviour. A recognised expert on the relationship between dopamine signalling and behaviour, Paton recently launched a Michael J. Fox Foundation-funded project investigating the neural basis of impulse control disorders – a common side effect of dopamine replacement therapy – in a mouse model of Parkinson’s disease.
Most cancers display abnormal sugars – known as glycans – on the surface of their cells. These tumour-associated glycans act as a molecular disguise, allowing cancer cells to avoid immune detection. Despite their clinical potential, these structures have long resisted immune targeting because they fail to engage the molecular pathways required to trigger strong T- and B-cell responses.
The GlycoTARGET project seeks to overcome this limitation by creating GlycoDISCs, tiny lipid-based nanodiscs engineered to present glycans to the immune system in a way that makes them visible and immunogenic. By precisely delivering these glycans to specialised subsets of dendritic cells – the sentinels that initiate adaptive immune responses – while co-delivering helper T-cell epitopes and immune stimulants, GlycoDISCs are designed to elicit coordinated antibody and cellular responses against tumours. This innovative platform could open a new front in cancer immunotherapy, transforming poorly immunogenic glycans into potent therapeutic targets.
“Our approach combines fundamental immunology with cutting-edge nanotechnology”, explains Carlos Minutti, Principal Investigator of the Immunoregulation Lab at the Champalimaud Foundation. “Support from the La Caixa Foundation will allow us to turn one of cancer’s stealthiest features – its sugar coat – into an Achilles’ heel. By making these glycans visible to the immune system, we hope to unlock new strategies for immunotherapy and antibody discovery”.
Beyond its therapeutic potential, GlycoTARGET is conceived as a versatile discovery platform: its modular nanodiscs can be rapidly adapted to display different glycans or other complex antigens, facilitating the design of novel vaccines, diagnostics, and immune-based therapies across a range of diseases.
This project is being carried out in collaboration with partners in Spain, including the Asociación Centro de Investigación Cooperativa en Biociencias–CIC bioGUNE, the Universidad del País Vasco (UPV/EHU), the Asociación Instituto de Investigación Sanitaria Biogipuzkoa, and the Universitat Rovira i Virgili.
Carlos Minutti began his PhD at the Complutense University of Madrid and continued his doctoral research at the University of Edinburgh with Prof. Judith Allen. Following postdoctoral training with Dr Dietmar Zaiss (Edinburgh) and Prof. Caetano Reis e Sousa (Francis Crick Institute), he established the Immunoregulation Laboratory at the Champalimaud Foundation in 2023, supported by an ERC Starting Grant, an EHA Kick-Off Grant and now a “la Caixa” Health Grant. His group studies how the immune system anticipates rather than merely reacts – how dendritic-cell diversity is programmed in the bone marrow to shape immune readiness across tissues. This focus on immune anticipation provides the conceptual backbone of GlycoTARGET: by understanding and harnessing the innate logic of dendritic-cell programming, the team aims to design smarter immunotherapies that prepare the immune system to recognise cancer before it can hide.
T cells genetically engineered with chimeric antigen receptors (CARs) are a new form of immunotherapy with an improved ability to target cancer cells. CARs are synthetic proteins created to enhance T cells’ ability to recognise and attack tumour cells by directing them to target any chosen molecule on the surface of malignant cells. Although CAR T cells targeting the CD19 molecule have shown remarkable success in patients with B-cell leukaemias and lymphomas, their effectiveness against other cancers – particularly solid tumours – has so far been limited.
One of the main obstacles has been the lack of CARs capable of targeting markers found on malignant cells but not on healthy cells. This project proposes a new solution: instead of targeting overexpressed proteins that are also present in healthy cells, the team will engineer CAR T cells to recognise chondroitin sulfate, a type of glycan found almost exclusively on cancer cells.
The goal is to generate a novel CAR capable of recognising this cancer-specific form of chondroitin sulfate, creating an immunotherapy that can detect different subtypes of cancer cells, while minimising toxicity to healthy tissues. By creating this new CAR, the team expects to pave the way for a novel cell therapy platform with greater tumour specificity and fewer side effects.
“Our preliminary data shows that our first CAR design already produces interesting anti-tumour responses against both solid and blood cancers in the lab”, says João Lacerda, Principal Investigator at GIMM. “This funding will be crucial for performing the full preclinical validation of our proposed therapy. By the end of the project, we aim to have an optimised CAR construct ready to move towards clinical application”.
João Lacerda is Director of a translational research group at GIMM focused on the intersection between haematology, immunology, and cellular therapies. The research team has concentrated primarily on the development of cellular therapies and clinical trials in the field of haematology and haematopoietic stem cell transplantation (HSCT), as well as the preclinical development of novel CAR T cell strategies. Lacerda is also Director of the Haematology and Bone Marrow Transplant Service at ULS Santa Maria and Full Professor at the Faculty of Medicine, University of Lisbon.
The ends of our chromosomes, called telomeres, can sometimes be mistaken for broken DNA, triggering inappropriate repair processes that cause genome instability and may lead to cancer. To prevent this, a specific set of proteins assembles at telomeres to suppress DNA repair activities. However, when real damage occurs within a telomere, it must still be repaired to prevent the accumulation of broken chromosome ends. How cells manage this delicate balance between protection and repair remains poorly understood.
This project seeks to address that question by focusing on a telomeric RNA molecule called TERRA, which is thought to help reorganise telomeric chromatin to enable proper repair. The team will combine biochemical, cellular, and molecular biology approaches with high-throughput screening to study how interactions between TERRA and telomeric proteins influence telomere repair and genome stability.
“This funding gives us the opportunity to address very fundamental questions in genome biology”, says Claus Azzalin, Group Leader at GIMM. “By deepening our understanding of how telomeres are maintained, this project could yield new insights into the mechanisms of cancer development, ageing, and age-related diseases – and potentially reveal new avenues for therapeutic intervention”.
Claus Azzalin earned his PhD in Genetics and Molecular Biology from the University of Pavia in 2000. After postdoctoral research at the Memorial Sloan-Kettering Cancer Center in New York and the Swiss Institute for Experimental Cancer Research in Lausanne, he became Assistant Professor for Genome Stability at ETH Zurich. In 2016, he joined what is now GIMM in Lisbon as Group Leader of the Telomeres and Telomere Transcription in Cancer and Ageing Unit, and since 2021 he has also served as Invited Associate Professor at the University of Lisbon’s Faculty of Medicine. During his postdoctoral work, Azzalin discovered that mammalian telomeres are transcribed into a long non-coding RNA called TERRA, a key player in telomere and genome stability. His group continues to explore TERRA’s biological roles in normal and disease contexts, including cancer and ageing. He has received multiple international distinctions, including the EMBO Young Investigator Award and an EMBO Installation Grant, and is co-founder of TessellateBio, a precision oncology start-up based in the Netherlands.
The “la Caixa” Foundation has allocated a total of €26 million for 34 projects from Portugal & Spain. This funding will support scientific studies over the next three years.
For this edition of the contest, 714 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 €1.8 million.
The financial aid provided to the chosen projects is categorised into two brackets:
Since its inception in 2018, the “La Caixa” Foundation has dedicated €172.3 million to 234 innovative research projects with significant societal impact. Of these, 72 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.
