The Institute for Research Sant Pau (IR Sant Pau) has held a new edition of its Research Day, an annual event that consolidates the center as a leading reference in biomedical research and innovation at the service of health. The event, held in the auditorium of Hospital de Sant Pau, brought together researchers, healthcare professionals, institutional representatives, and experts from the research system to reflect on the major challenges and opportunities of hospital-based research.

The day was opened by Dr. Jordi Surrallés, Scientific Director of the IR Sant Pau, who welcomed attendees. Dr. Surrallés framed the meeting within the rollout of the 2025–2030 Strategic Plan, the year in which the strategic reflection initiated in recent years begins to translate into action and to transform the way IR Sant Pau operates. In his address, Dr. Surrallés also emphasized that «research cannot turn its back on society. Generating excellent knowledge is essential, but it is not enough: explaining what we do, why we do it, and what impact it has is part of our responsibility as a public research institution».

The Role of Philanthropy in the Biomedical Research Ecosystem

One of the first axes of the day was a discussion on the role of philanthropy in building the biomedical research ecosystem, with a lecture focused on analyzing how philanthropic support can make a decisive contribution to research development, especially in areas of high scientific and social impact.

The lecture was delivered by Àngel Font, Associate Director of Research and Fellowships at the “la Caixa” Foundation and Executive Director of the CaixaResearch Institute, who explained how the foundation provides sustained support for scientific and biomedical research, positioning it as a strategic priority. In this context, Font presented the CaixaResearch Institute as an example of how philanthropy can strengthen research excellence, foster collaboration between centers, and contribute to consolidating a competitive and sustainable research ecosystem, also at the European level.

This was followed by a roundtable discussion moderated by Dr. Jordi Surrallés and focused on the challenges and opportunities of hospital research institutes, with the participation of Dr. Begoña Benito, Director of the VHIR; Dr. Gabriel Capellá, Director General of the IDIBELL; Dr. Jordi Barretina, Director General of the IGTP; and Dr. Antoni Plasencia, Director General for Research and Health Innovation at the Department of Health of the Government of Catalonia. During the discussion, key issues were addressed such as the sustainability of research institutes, talent attraction and retention, and the need to strengthen environments that facilitate research excellence integrated within hospitals.

Independent Clinical Research in the Spotlight

The central session of the morning was devoted to the value of independent clinical drug research, with the presentation of several academic clinical trials led by IR Sant Pau and funded through the Independent Clinical Research (ICI) call of the Instituto de Salud Carlos III. This session featured, among others, a multicenter, randomized, double-blind trial with donepezil in mild cognitive impairment associated with Parkinson’s disease; the AFAN trial, focused on repositioning afatinib in oral cancer in patients with Fanconi anemia; a study on the antidepressant effects of psilocybin analyzed through functional neuroimaging; the LESS-AD trial, with levetiracetam to prevent epileptic seizures in adults with Down syndrome and Alzheimer’s disease; several trials with academic CAR-T cells in hematologic neoplasms; and the SAVE trial, which compares sevoflurane and propofol in general anesthesia in patients with ischemic stroke treated with endovascular therapies.

This set of presentations highlighted IR Sant Pau’s role in the development of academic and multicenter clinical trials, with a clear translational orientation. In the words of Dr. Surrallés, «Sant Pau’s distinctive feature is the ability to integrate disciplines, connect basic and clinical research, and always keep the focus on the patient».

New Leadership for Translational Research

The day continued with a session dedicated to new leadership in translational research, led by early-career researchers with emerging trajectories linked to competitive national investigator stabilization programs. This session showcased projects addressing some of the major current challenges in biomedical research from a clearly translational perspective.

Specifically, initiatives were presented focusing on the application of data science to integrate environmental, infectious disease, and clinical data in health research; on modulating the tumor microenvironment to improve therapeutic outcomes in solid tumors; on integrating omics, clinical, and epidemiological approaches in women’s health; on advancing neuropsychological assessment in people with Down syndrome in the digital era; and on developing precision psychiatry strategies based on brain circuits.

This session reinforced IR Sant Pau’s commitment to scientific talent development and to creating opportunities for new generations of researchers to lead high-impact projects. As emphasized by the Institute’s Scientific Director, «the Strategic Plan places talent, career paths, and organizational culture at the center, because there is no research excellence without teams that are supported, recognized, and have a future perspective».

Research Explained in Four Minutes

One of the main new features of this edition of the Research Day was the first-time inclusion of the outreach activity “240 seconds: my thesis in a flash”, which closed the day in the afternoon. This initiative gave prominence to doctoral candidates, who were challenged to explain their research orally in a maximum of four minutes, using clear, accessible language understandable to a non-specialist audience.

The activity was conducted in a format of consecutive short presentations, in which participants had to synthesize the objectives, methodology, and relevance of their research, emphasizing its application and potential impact. With this dynamic format, the session highlighted young researchers’ communication skills and contributed to bringing the research carried out at IR Sant Pau closer to the center’s scientific community and to society as a whole.

Immune Neoplasms and Targeted Therapies

The closing lecture of the morning block was delivered by Dr. Ari Melnick, Director of the Josep Carreras Leukaemia Research Institute, who presented a talk focused on pathogenesis and targeted therapies in immune neoplasms.

In his presentation, Dr. Melnick addressed the molecular and immunological mechanisms involved in the development of these diseases, as well as recent advances in targeted therapies and their translational potential in clinical practice, highlighting how mechanistic knowledge is opening the door to increasingly specific and personalized treatments in the field of hematologic neoplasms.

The day concluded with an institutional closing ceremony with the participation of Dr. Adrià Comella, Managing Director of Hospital de Sant Pau, and Dr. Jordi Surrallés, Scientific Director of IR Sant Pau, during which reflections were shared on the present and future challenges of hospital-based research. With this new edition of the Research Day, IR Sant Pau reaffirms its commitment to scientific excellence, independent research, and knowledge transfer, consolidating its position as a key player within the biomedical research system and as a driver of continuous improvement in healthcare. In his closing message, Dr. Surrallés recalled that «2025 is not an endpoint. It is a starting point. The challenge now is to consolidate the transformation, stay the course, and do it together».

Researcher Alejandra Pérez, a nursing professional affiliated with the Sant Pau Research Institute (IR Sant Pau), has been awarded a grant from the Official College of Nurses of Barcelona (COIB) to develop a research project focused on the assessment of quality of life in premature infants or those with low birth weight for gestational age, as well as that of their families, enrolled in the Neonatal Home Care Program (PADN).

The main objective of the project is to design and validate a specific scale that allows for rigorous measurement of quality of life in this care setting, a key dimension for assessing the real impact of care beyond traditional clinical indicators. At present, there are no validated instruments specifically designed to assess the quality of life of these infants during home follow-up after hospital discharge.

“Neonatal home care has demonstrated clear clinical benefits, but we still have very few tools that allow us to assess how infants and their families experience this stage,” explains Alejandra Pérez. “Having a validated scale will help us systematically incorporate quality of life as a relevant indicator in the evaluation of these programs and in the improvement of care.”

The research is structured in several complementary phases. First, a systematic review of the scientific literature will be conducted to identify the components that define the quality-of-life construct in premature infants and those with low birth weight. The project will then incorporate a qualitative study with a phenomenological approach, based on in-depth interviews with families enrolled in the PADN, with the aim of exploring their experiences and perceptions regarding their children’s quality of life and the family environment.

Based on these findings, the scale will be designed and subsequently undergo psychometric validation, involving expert participation and statistical analysis of its reliability and validity. This process will result in a specific, robust tool applicable to clinical practice, aimed at improving the assessment and follow-up of infants cared for in neonatal home hospitalization programs.

The project involves a research team composed primarily of nursing professionals, with the participation of neonatology specialists, and it addresses ethical and confidentiality aspects transversally, with the corresponding review by a research ethics committee. It also includes a detailed work plan and a dissemination strategy designed to facilitate the transfer of results to both clinical practice and the scientific community.

The awarding of this grant strengthens the role of nursing research at IR Sant Pau and its commitment to projects that place patients and their families at the center of health care, promoting a more comprehensive and humanized evaluation of care.

The Institut de Recerca Sant Pau (IR Sant Pau) has led a multicenter study showing that incorporating the biomarker NT-proBNP, commonly used to assess cardiac function, significantly improves the ability of the angiogenic sFlt-1/PlGF ratio to predict preeclampsia in the short term. The study, published in Clinical Chemistry, demonstrates that integrating both biomarkers makes it possible to refine risk stratification in women with clinical suspicion of the disease.

Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of maternal–fetal morbidity worldwide. The sFlt-1/PlGF ratio allows the disease to be ruled out when values are below 38, but above 38 its interpretation becomes less conclusive and requires close follow-up and additional assessments. The main challenge lies in managing cases with an sFlt-1/PlGF ratio between 38 and 84, where diagnostic and management uncertainty is greatest. As explained by Dr. Carmen Garrido, clinical head of Obstetrics at Hospital Sant Pau and collaborating researcher in the Perinatal and Women’s Medicine group at IR Sant Pau, “It is in this intermediate diagnostic range where NT-proBNP provides an additional answer that allows us to guide both the case and follow-up much more effectively.

How the Study Was Designed and What Each Predictive Model Contributed

To assess the added value of NT-proBNP, the team developed three predictive models based on different thresholds of the angiogenic ratio. The first re-evaluated cases with values above 38 by incorporating the cardiac biomarker. The second examined its usefulness at values above 85, traditionally associated with higher clinical risk. The third focused exclusively on the 38–84 range, an interval that is particularly complex from a diagnostic standpoint. This last model showed the most robust performance, as it made it possible to better discriminate between patients who would progress to preeclampsia and those who would not, improving short-term prediction of the disease.

According to Dr. Carmen Garrido, “These models allowed us to clearly identify the situations in which NT-proBNP provides decisive information, especially when the angiogenic ratio alone does not resolve the diagnostic uncertainty.”

To determine the clinical applicability of these models, the study assessed their performance across different clinical scenarios of preeclampsia: early-onset (before 34 weeks), preterm (before 37 weeks), term (after 37 weeks), and cases with maternal or fetal complications. This approach made it possible to verify whether the benefit of combining markers was maintained across all contexts or was particularly notable in specific profiles. According to Dr. Madalina Nicoleta Nan, staff biochemist at Hospital Sant Pau and researcher in the Perinatal and Women’s Medicine group, “Stratification by clinical scenario allowed us to confirm that combining NT-proBNP with the angiogenic ratio is especially valuable in predicting early-onset preeclampsia and higher-risk forms, where disease progression can accelerate in a very short time.”

The Combination of Markers Improves Prediction and Reduces Clinical Uncertainty

The study, conducted in 316 women with clinical suspicion of preeclampsia and based on the analysis of 424 samples, shows that NT-proBNP levels are significantly elevated in those who will develop preeclampsia within the following seven days. Integrating this biomarker with the angiogenic ratio maintains a negative predictive value of 99.5%, while improving the positive predictive value. This increases from 35.4% when using the sFlt-1/PlGF ratio alone to 60.7% for predicting early-onset preeclampsia one week before the appearance of clinical manifestations. This combination provides high reliability for ruling out the disease in the short term and makes it possible to prioritize surveillance for cases that are truly likely to progress.

In addition, the combination adds a complementary pathophysiological dimension: the angiogenic ratio reflects placental dysfunction, while NT-proBNP provides information on the degree of maternal cardiovascular stress, a factor closely linked to the risk of clinical deterioration. “Combining markers that inform on different processes,” explains Dr. Garrido, “helps us more precisely identify the patients who need intensified follow-up and avoid unnecessary interventions in those who do not.”

The usefulness of NT-proBNP is particularly evident in cases where the angiogenic ratio shows intermediate values and its diagnostic capacity is more limited. As detailed by Dr. Garrido, “NT-proBNP allows us to distinguish whether we are dealing with a patient at real risk of progression or whether a less intensive monitoring approach can be considered,” information that is essential for tailoring clinical decisions more accurately.

A Tool That Helps Anticipate Severe Complications

The analysis carried out in the study reveals that combining both biomarkers also makes it possible to anticipate complications and predict short-term clinical evolution. Women with abnormal values in both markers show a mean latency to delivery of 1.3 weeks, indicating closer proximity to decompensation and the need to intensify surveillance and prepare interventions in advance.

As highlighted by Dr. Madalina Nicoleta Nan, “When both markers are elevated, progression toward the need to end the pregnancy is usually faster, and having this information allows us to plan care more effectively.” Conversely, she adds, “If the angiogenic ratio is high but NT-proBNP remains low, this usually reflects placental alteration that does not imply preeclampsia requiring imminent delivery, allowing us to avoid hasty interventions.”

A Complementary, Accessible, and Easy-to-Implement Biomarker

The research team emphasizes that NT-proBNP does not replace the angiogenic ratio but rather complements it by providing relevant clinical information in cases where sFlt-1/PlGF is inconclusive. This complementarity facilitates more precise decision-making, allows follow-up to be tailored according to risk profile, and offers a high-value tool for clinical practice. In addition, NT-proBNP is an accessible, low-cost, and widely available test, which would facilitate its incorporation into care protocols.

Although the results need to be validated in larger and more diverse cohorts, they represent a significant advance in the early prediction of preeclampsia and open the door to multimarker diagnostic strategies with greater precision and real-world applicability. IR Sant Pau thus consolidates its leadership in perinatal research and in the development of diagnostic tools aimed at safer and more personalized care.

Reference Article:

Garrido-Giménez C, Nan MN, Cruz-Lemini M, García-Manau P, Garcia-Osuna Á, Ullmo J, Mora J, Sánchez-García O, Medina-Mallén MDC, Chóliz M, Platero J, Llurba E, EuroPE Working Group. Can NT-proBNP enhance the accuracy of angiogenic factors in the short-term prediction of preeclampsia? Clin Chem 2025;72:206–16. https://doi.org/10.1093/clinchem/hvaf135

The Sant Pau Research Institute (IR Sant Pau) has received funding from the Carlos III Health Institute (ISCIII), co-funded by the European Union through European Funds, for the technological development of OptimAP. This project is aimed at improving the use of antibiotics in acute respiratory infections in children seen in primary care.

The grant is part of the 2025 call for Health Technology Development Projects within the Strategic Action in Health (AES). Its objective is to accelerate the transfer of research results to the healthcare system and to promote innovative solutions with a real impact on clinical practice.

Acute respiratory infections are one of the leading reasons for pediatric consultations and a frequent cause of antibiotic prescribing, often unnecessarily. This situation contributes to the rise of antimicrobial resistance, one of today’s major public health challenges. In this context, OptimAP proposes an innovative intervention to reduce unnecessary antibiotic prescribing without compromising safety or quality of care.

The project is led by Dr. Pablo Alonso Coello, head of the Clinical Epidemiology and Health Services research group at IR Sant Pau, and combines two complementary strategies: a communication skills training program for primary care professionals and a digital tool aimed at families, designed to improve understanding of respiratory infections and to facilitate shared decision-making.

The development of OptimAP, including its evaluation through a clinical trial under real-world clinical practice conditions, was previously funded thanks to a grant from La Marató de TV3. The results demonstrated a significant reduction in antibiotic use with no increase in complications or loss of family satisfaction.

With the current funding, totaling €147,620, the project will focus on final validation, technological optimization, and the assessment of the tool’s clinical, organizational, and economic impact. It will also focus on the analysis of regulatory and feasibility aspects to facilitate its implementation and scalability within the healthcare system.

Through this initiative, IR Sant Pau strengthens its commitment to the development of innovative solutions that contribute to more rational antibiotic use and to the fight against antimicrobial resistance in pediatric primary care.

A multidisciplinary team has uncovered a key mechanism that allows the human bacterium Mycoplasma pneumoniae—responsible for atypical pneumonia and other respiratory infections—to obtain cholesterol and other essential lipids directly from the human body. The discovery has been published in Nature Communications. The research was co-led by Dr. Noemí Rotllan, from the Sant Pau Research Institute (IR Sant Pau) and the Center for Biomedical Research in Diabetes and Associated Metabolic Disorders (CIBERDEM); Dr. Marina Marcos, from the Autonomous University of Barcelona (UAB); and Dr. David Vizarraga, from the Institute of Molecular Biology of Barcelona of the Spanish National Research Council (IBMB-CSIC) and the Center for Genomic Regulation (CRG). Overall coordination was led by Dr. Joan Carles Escolà-Gil, from IR Sant Pau and CIBERDEM; Dr. Jaume Piñol, from UAB; and Dr. Ignacio Fita, from IBMB-CSIC. The study also involved collaboration from the Institute of Biotechnology and Biomedicine of the UAB (IBB-UAB), the Center for Biomedical Research in Cardiovascular Diseases (CIBERCV), and other leading institutions.

Dr. Joan Carles Escolà-Gil explains that “the bacterium uses the P116 protein as a highly effective tool to capture cholesterol and other essential lipids from the host, a mechanism that allows it to survive and colonize tissues beyond the lung.” He adds that “understanding this process opens new avenues to block its growth and to explore biotechnological applications based on its affinity for lipid-rich tissues.”

This discovery is particularly relevant because Mycoplasma pneumoniae is primarily known as a respiratory bacterium, yet several studies—including this one—show that it can reach other tissues in the body, especially those with a lipid-rich environment. Understanding how it achieves this extra respiratory colonization helps explain clinical manifestations outside the lung and provides clues about its potential contribution to systemic inflammatory processes.

P116, a Bacterial System for Cholesterol Uptake

Unlike other bacteria, Mycoplasma pneumoniae cannot synthesize many lipids that are essential for the integrity of its membrane, including cholesterol, and therefore depends entirely on the host to survive. In this context, the new study demonstrates that the P116 protein acts as a highly efficient lipid uptake system, capable of extracting cholesterol and other lipid species from both human lipoproteins—including LDL and HDL—and different cell types.

Experiments conducted by the team show that P116 rapidly incorporates cholesterol from LDL and HDL but can also capture phosphatidylcholines, sphingomyelins, and triacylglycerols. This ability to recognize and absorb multiple types of lipids makes P116 an essential mechanism for the survival of the microorganism. By supplying its membrane with components obtained directly from the host, Mycoplasma pneumoniae can adapt to different environments in the body and colonize tissues with a high lipid content beyond the respiratory system.

Dr. Noemí Rotllan highlights the biological significance of this finding: “P116 acts as a lipid entry gate for the bacterium, an extraordinarily versatile system that allows it to incorporate cholesterol, phospholipids, and sphingolipids from the host.” She adds that “this broad lipid uptake capacity largely explains why Mycoplasma pneumoniae can survive in such diverse environments and localize to tissues where other bacteria would not be able to thrive.”

An Antibody That Slows Growth and Adhesion

The study also reveals that a monoclonal antibody specifically directed against the C-terminal domain of P116 markedly blocks cholesterol uptake by the bacterium, a process essential for its survival. “By preventing P116 from functioning as a lipid entry system, the antibody significantly reduces the growth of Mycoplasma pneumoniae in cell cultures and limits its ability to adhere to human atherosclerotic lesions in ex vivo samples. This dual action—slowing bacterial proliferation and preventing its presence in vulnerable areas of the cardiovascular system—represents a major advance in understanding the pathogenic and extra respiratory role of this microorganism,” notes Dr. Marina Marcos, a researcher at UAB.

The researchers emphasize that preventing this adhesion is particularly relevant because the presence of Mycoplasma pneumoniae in vulnerable plaques could promote local inflammation and compromise lesion stability. Unstable plaques are more prone to rupture, a process that can trigger serious cardiovascular events.

Dr. Joan Carles Escolà-Gil underscores its potential: “The antibody targets the bacterium’s key point, which is its ability to capture cholesterol. By blocking P116, we slow its growth and prevent it from adhering to atherosclerotic lesions.” He adds that “this is relevant because the presence of Mycoplasma pneumoniae in vulnerable plaques could contribute to inflammation and compromise their stability. Preventing this adhesion offers an opportunity to further protect tissues affected by atherosclerosis.”

A Biotechnological Tool to Target Therapies

The researchers have also used a modified and harmless form of the bacterium, designed to serve as a biotechnological tool to study how it distributes within the body. This version of the microorganism retains its natural ability to localize to lipid-rich tissues but has been adapted so that it does not cause disease. In experiments with hypercholesterolemic mice, the modified bacterium selectively accumulates in the liver and in atherosclerotic plaques, making it a potential vehicle for delivering therapeutic molecules or diagnostic agents precisely to the tissues where they are most needed.

This capacity for specific targeting opens a promising avenue in an emerging area of biotechnology: the use of modified living microorganisms as systems for targeted delivery of therapeutic molecules. In the case of Mycoplasma pneumoniae, its minimalist metabolism and dependence on host lipids make it particularly attractive as a manipulable and safe platform.

Dr. Noemí Rotllan summarizes it as follows: “The modified version of Mycoplasma pneumoniae shows a natural tropism toward the liver and atherosclerotic lesions, making it a promising biotechnological platform for the study and treatment of metabolic and cardiovascular diseases.” She adds that “leveraging the biology of this microorganism in a controlled way allows us to envision targeted therapeutic strategies that are more precise and potentially more effective for acting on tissues affected by atherosclerosis or fatty liver disease.”

A Conceptual Advance and a Top-Level Scientific Collaboration

Beyond its biomedical relevance, the study provides a conceptual advance in understanding Mycoplasma pneumoniae, a pathogen with one of the smallest known bacterial genomes, which depends heavily on the host to obtain essential lipids. Identifying P116 as a fundamental mechanism of lipid uptake opens new avenues for the development of antimicrobial therapies and vaccines.

Scientists from the Joint Electron Microscopy Center at the ALBA Synchrotron, the University of Navarra Clinic, and the Navarra Health Research Institute (IdiSNA) also participated in the research. They contributed to the structural characterization of P116, the analysis of its interaction with antibodies, and imaging and biodistribution studies in animal models.

The work strengthens a multidisciplinary scientific collaboration among leading centers in structural biology, microbiology, cardiometabolism, and biomedical imaging. It places this line of research at the forefront of the design of new biotechnological tools based on modified microorganisms to study and intervene in metabolic and cardiovascular diseases.

Reference Article:

Vizarraga D, Marcos M, Rotllan N, Martín J, Santos D, Camacho M, Soto B, Velasco-Reniu L, Guerra P, Pareja F, Collantes M, Wu W, Rodríguez-Arce I, Serrano L, Piñol J, Fita I, Escolà-Gil JC. Sources of essential lipids for Mycoplasma pneumoniae via P116 to target liver and atherosclerotic lesions. Nat Commun 2025;16:11159. https://doi.org/10.1038/s41467-025-66129-5

The Institut de Recerca Sant Pau (IR Sant Pau) has been awarded three research activity intensification grants in the 2025 call of the Instituto de Salud Carlos III (ISCIII). This program is aimed at healthcare professionals with an established scientific track record and seeks to relieve their clinical workload partially so they can devote a greater proportion of their time to research, without compromising patient care.

These grants make it possible to more closely integrate research into clinical practice, fostering the development of projects focused on improving the diagnosis, treatment, and prognosis of highly complex diseases. In this edition, the grant recipients are Dra. Ana Aulinas, Dr. Luis Prats Sánchez, and Dr. Ricardo Rojas-García, whose projects represent strategic areas of biomedical research at IR Sant Pau.

Dra. Ana Aulinas, a specialist in endocrinology and nutrition, focuses her research activity on hypothalamic and pituitary disorders, a group of rare conditions characterized by low prevalence and high diagnostic and therapeutic complexity. Dra. Aulinas coordinates the Functional Unit for Pituitary Disorders, a multidisciplinary unit that operates within the European Reference Network on Rare Endocrine Conditions (EndoERN). The unit is nationally recognized as a CSUR center for the diagnosis and treatment of complex pituitary disorders and is part of the XUEC for rare endocrine diseases. Thanks to this grant, she will be able to combine patient care for pituitary disorders with clinical and translational research in this field, within the framework of project PI24/01428. This project focuses on the study of comorbidities associated with hypothalamic damage and hypopituitarism and their relationship with the neurohormone oxytocin. In this way, IR Sant Pau’s participation is strengthened in projects aimed at improving the diagnosis and treatment of hypothalamic and pituitary diseases, as well as the quality of life of affected individuals.

Dr. Luis Prats Sánchez, a neurologist, is a member of the IR Sant Pau research group on cerebrovascular diseases and actively participates in the RICORS-ICTUS network. His work focuses on hemorrhagic stroke, with particular interest in the mechanisms that determine clinical outcomes and neurological recovery. With the support of this intensification grant, he will be able to expand his dedication to translational research and consolidate projects such as END-GROWTH (PI24/01009), which will compare best medical therapy with and without endovascular treatment. This will determine which strategy best predicts hematoma growth in patients with spontaneous intracerebral hemorrhage.

Meanwhile, Dr. Ricardo Rojas-García, consultant physician in the Department of Neurology, will carry out his work within the framework of project PI23/00845, focused on amyotrophic lateral sclerosis (ALS). This intensification allows him to combine clinical activity with research in neuromuscular and neurodegenerative diseases, strengthening IR Sant Pau’s participation in studies that apply molecular biology and biomarker analysis to improve understanding of the disease. His expanded dedication will help advance clinical research in ALS and generate results with the potential for direct impact on the care of affected individuals.

The awarding of these three intensification grants reinforces IR Sant Pau’s commitment to applied clinical research and the promotion of clinical scientific talent. These projects, developed in close collaboration with the services of Hospital de Sant Pau, will contribute to generating knowledge that directly translates into improved patient care and advances in translational medicine.

The Sant Pau Research Institute (IR Sant Pau) will lead two new independent clinical trials in areas of high clinical complexity—hematologic oncology and acute ischemic stroke—after securing more than €2.5 million in competitive public funding through the 2025 Independent Clinical Research Projects (ICI) call of the Carlos III Health Institute (ISCIII). Both studies will be conducted in the hospital setting and address unmet clinical needs, with the aim of generating robust scientific evidence to improve the therapeutic management of patients with severe, high–public health–impact diseases.

The projects, promoted from the academic sphere and with no commercial interest, are aligned with a model of independent clinical research designed to answer questions that are relevant to clinical practice. This approach enables the generation of knowledge that is directly applicable to the clinical setting, reduces variability in therapeutic decision-making, and contributes to more precise, evidence-based medicine.

A New Academic CAR-T Therapy for Patients With Refractory Hodgkin Lymphoma

One of the funded projects is led by Dr. Javier Briones, director of the Oncology Hematology and Transplant Research Group at IR Sant Pau and director of the Hematology Department at Sant Pau Hospital, with total funding of €1,805,657.59. Through a phase I/II clinical trial, the study will evaluate a fourth-generation academic CAR-T therapy developed entirely at Sant Pau for the treatment of patients with refractory classical Hodgkin lymphoma. This population has a particularly poor prognosis after failure of available therapies.

The cellular therapy, known as HSP-CAR30-CCR200, incorporates an innovative design aimed at counteracting tumor inhibitory mechanisms that limit the effectiveness of current CAR-T therapies and promote loss of response over time. The trial will assess treatment safety and its ability to induce deeper and more durable antitumor responses, with the goal of expanding therapeutic options for patients who currently have very limited alternatives.

Dr. Briones emphasizes that “this trial arises from the need to offer new therapeutic options to patients with Hodgkin lymphoma who no longer respond to available treatments; the study builds on the previous trial, a European pioneer, that we conducted with CART30 at our center. This new study allows us to introduce design improvements that increase its effectiveness and to evaluate its potential in a real-world clinical setting, with the ultimate goal of achieving more durable and clinically meaningful responses.”

This project builds on Sant Pau’s prior experience in the development of academic CAR-T therapies, integrating preclinical research, manufacturing of the cellular medicinal product in hospital facilities accredited according to international quality and safety standards, and its subsequent clinical evaluation in patients. This enables a rapid and safe translation from the laboratory to clinical practice.

Maximizing the Benefit of Thrombectomy in Ischemic Stroke Through Selection of the Optimal Anesthetic Protocol

The second awarded project, with total funding of €765,704.94, is led by Dr. Pol Camps, coordinator of the Cerebrovascular Diseases Group at IR Sant Pau and of the Stroke Unit at Sant Pau Hospital. It focuses on the management of acute ischemic stroke. The SAVE study is a multicenter clinical trial that will compare two general anesthesia strategies—sevoflurane and propofol—in patients undergoing mechanical thrombectomy, the standard-of-care treatment for the most severe strokes.

Although mechanical thrombectomy has represented a decisive advance in stroke treatment, important questions remain regarding optimal anesthetic management during the procedure and its impact on subsequent neurological outcomes. The trial will evaluate variables such as final cerebral infarct volume, functional recovery, and procedure safety, with the aim of providing evidence to optimize and standardize clinical protocols.

From a clinical care perspective, Dr. Camps notes that “thrombectomy has transformed the prognosis of acute ischemic stroke, but there are still aspects of the procedure that can influence clinical outcomes. This study seeks to generate solid evidence to determine the most appropriate anesthetic strategy and to help maximize the benefit of this treatment for patients who experience an ischemic stroke.”

The project will be carried out in collaboration with several public healthcare system hospitals, enabling the recruitment of a representative number of patients and ensuring the robustness of the results. Its multicenter design and practical orientation confer a high potential for immediate translation into clinical practice, with a direct impact on clinical decision-making and on the care of patients with acute ischemic stroke.

Independent Clinical Research Focused on Clinical Practice

With the launch of these two trials, IR Sant Pau strengthens its commitment to independent clinical research, driven from the public and academic sectors and focused on addressing clinically relevant questions for the healthcare system. This model makes it possible to generate high-value-added knowledge and to effectively translate it into the care setting, contributing to improvements in the quality, safety, and efficiency of patient care.

The Department of Health has awarded three grants under the PERIS 2025 program to intensify research activity to professionals from the Sant Pau Research Institute (IR Sant Pau). Each initiative will receive €149,760, representing a total investment of €449,280 aimed at promoting research lines that may transform the diagnosis, monitoring, and management of various neurological diseases.

PERIS strengthens research carried out within the healthcare system and enables professionals who combine clinical practice and research to have protected time to advance priority projects. In this call, the three proposals from IR Sant Pau focus on strategic areas for public health: the early detection of neurodegenerative diseases, improved diagnosis of rare disorders, and the management of a particularly relevant complication in Down syndrome.

Characterization of the Early Phases of the Alzheimer–Lewy Spectrum

One of the supported research lines focuses on understanding what happens in the brain long before symptoms of diseases such as Alzheimer’s disease or dementia with Lewy bodies become evident. The work led by Dr. Daniel Alcolea is based on an ambitious goal: to accurately describe the earliest phases of neurodegeneration and to understand how the pathological process begins. The study places particular emphasis on this initial phase—known as the prodromal stage—in which the brain already begins to undergo changes even though the individual has not yet developed symptoms.

To characterize this stage, the team combines multiple complementary sources of information, including cerebrospinal fluid and plasma biomarkers, recordings of brain activity, sleep studies, and high-resolution magnetic resonance imaging. This multimodal approach provides a comprehensive view of the process that precedes cognitive decline and makes it possible to identify patterns that would not be detectable using a single technique.

The project is structured in three successive phases that include the validation of cerebrospinal fluid and plasma biomarkers, the study of cohorts with differentiated biochemical profiles, and the integration of functional and imaging data. The ultimate goal is to build a reliable map of this silent yet decisive period, with the capacity to improve diagnostic stratification and lay the groundwork for future preventive or therapeutic interventions.

Plasma and Imaging Biomarkers for the Diagnosis of 4R Tauopathies

Another funded proposal addresses a key challenge in neurodegeneration: advancing early molecular diagnosis of the two main 4R tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Although they are often considered “rare” diseases, together they represent a frequent cause among patients who seek care for cognitive, behavioral, and motor impairment once Alzheimer’s disease has been ruled out.

At present, these diseases are frequently diagnosed when they are already in advanced, palliative stages, with a high degree of disability, and when clinical differentiation between PSP and CBD is particularly challenging due to symptom overlap and variability in presentation. The research led by Dr. Ignacio Illán-Gala proposes an innovative strategy based on the combination of novel imaging markers and plasma biomarkers, with the aim of shifting diagnosis toward minimally symptomatic stages. This shift is critical because it is precisely during these early phases that disease-modifying treatments are expected to be most effective.

The project will assess the performance of this multimodal approach both to increase diagnostic accuracy and to more reliably distinguish PSP from CBD in early stages. It will also examine the longitudinal evolution of these markers and their relationship with clinical progression. This knowledge may improve patient stratification, optimize the design of clinical trials, and ultimately move diagnosis toward a scenario in which care is earlier, more specific, and potentially more disease-modifying.

Epilepsy in Alzheimer’s Disease Associated With Down Syndrome

The third line of research addresses a particularly relevant challenge: the development of epilepsy in individuals with Down syndrome who develop Alzheimer’s disease, a phenomenon that accelerates cognitive decline and increases dependency. In the early stages, these seizures can be difficult to detect because they present in subtle ways.

The research coordinated by Dr. María Carmona-Iragui combines EEG, sleep studies, plasma biomarkers, and magnetic resonance imaging to identify early signs of cerebral hyperexcitability and to understand how this epileptic activity influences disease progression. This integrated approach makes it possible to describe phenomena that often go unnoticed in routine clinical practice.

This analysis is complemented by a phase III clinical trial designed to determine whether levetiracetam can prevent or delay the onset of seizures. This is a pioneering approach that could establish, for the first time, a preventive strategy for this population, with the potential to significantly improve quality of life.

With these three PERIS grants, IR Sant Pau strengthens its leadership in neurodegenerative research and consolidates its commitment to projects that combine scientific rigor, clinical utility, and direct impact on people’s health. Although they address different challenges, these initiatives share a common orientation: translating scientific knowledge into clinical practice to improve early detection, anticipate disease progression, and open new therapeutic opportunities.

Therapy-related myeloid neoplasms represent one of the most significant current challenges in hematologic oncology due to their biological complexity, their aggressive clinical course, and the limited effectiveness of conventional treatments. In this context, biomedical research is seeking new strategies that make it possible to move toward more precise approaches tailored to the characteristics of each patient.

Along these lines, an international research project is being carried out with the participation of the Sant Pau Research Institute (IR Sant Pau), focused on the development of precision medicine strategies to improve the management of this type of hematologic cancer. The study is led by Dr. Manel Esteller, head of the Cancer Epigenetics group at IR Sant Pau, and has received a competitive grant from the Instituto de Salud Carlos III (ISCIII). This is within the framework of the 2025 International Collaboration Projects call of the Strategic Action in Health.

The project will have a total budget of €300,000 and will be carried out over three years (2026–2028), within the context of the European program EP PerMed (European Partnership for Personalised Medicine), which promotes innovative approaches based on pharmacogenomics and the personalization of treatments.

A Molecular Approach to a Highly Complex Hematologic Cancer

Therapy-related myeloid neoplasms arise because of previous oncologic treatments and are characterized by marked molecular heterogeneity, which complicates their clinical management and limits responses to standard therapies. This biological diversity makes it particularly necessary to gain more in-depth insight into the mechanisms underlying the disease and their relationship with treatment response.

In this regard, the project proposes an advanced molecular characterization of the disease with the aim of identifying biological profiles that enable improved patient stratification and optimized therapy selection. “Gaining an in-depth understanding of the molecular alterations that characterize these neoplasms is key to moving toward more effective treatments tailored to each patient, especially in a clinical context as complex as that of therapy-related myeloid neoplasms,” explains Dr. Esteller.

To this end, the study will integrate state-of-the-art genomic and transcriptomic technologies, including single-cell analyses, advanced sequencing, and multi-omics analysis strategies, which will provide a detailed view of the biological processes involved in the disease.

Advanced Analysis and International Collaboration

The work will be carried out in collaboration with other national and international research groups within the framework of the networks promoted by EP PerMed. It will make extensive use of scientific infrastructures specialized in genomics, data analysis, and sequencing platforms. This approach will make it possible to obtain an integrated view of the molecular mechanisms involved in the disease and their impact on therapeutic response.

The funding awarded will be used primarily to cover costs associated with advanced scientific services, such as specialized sequencing, the processing, and analysis of large data volumes, international project coordination, and the dissemination of results at scientific conferences. It also covers open-access publications.

Advancing Research in Precision Medicine

The participation of IR Sant Pau in this project reinforces its commitment to translational research and precision medicine. It also involves international initiatives aimed at improving the diagnosis, prognosis, and treatment of complex oncologic diseases through personalised approaches based on molecular knowledge of the disease.

The Sant Pau Research Institute (IR Sant Pau) has obtained two Sara Borrell contracts in the 2025 call of the Instituto de Salud Carlos III (ISCIII), within the framework of the Strategic Action in Health. These grants, aimed at postdoctoral researchers, are designed to support the continuity and consolidation of scientific careers in the field of biomedical research within the National Health System.

The grants have been awarded to Dr. Víctor de la Peña Arteaga and Dr. Iñigo Rodríguez Baz, who will carry out their research activities at IR Sant Pau. Here they will be able to deepen their scientific specialization and advance their research careers in an accredited healthcare research environment.

In the case of Dr. Víctor de la Peña Arteaga, the contract will make it possible to consolidate his research in the field of mental health, with a neurobiological and translational approach focused on treatment-resistant depression. This is within a line of work coordinated by Dr. Narcís Cardoner. His research activity focuses on studying the brain mechanisms involved in therapeutic response, with particular attention to the factors associated with the lack of response to conventional antidepressant treatments.

In this context, Dr. de la Peña’s research includes the identification and validation of biomarkers of functional neuroimaging linked to the clinical evolution of patients with treatment-resistant depression. Integrating this strategy into a clinical setting helps deepen the biological and functional characterization of the disorder and contributes to a more profound understanding of its underlying mechanisms, an area of significant clinical and social impact.

For his part, Dr. Iñigo Rodríguez Baz will conduct his research in the field of dementia, with a specific focus on Lewy body dementia, within a research line coordinated by Dr. Daniel Alcolea. His research centers on the clinical and biological phenotyping of the disease, including its prodromal phases, with the goal of describing its clinical and evolutionary heterogeneity with greater precision.

His work integrates the analysis of biomarkers in different biological fluids—plasma, serum, and cerebrospinal fluid—with neuroimaging and neurophysiological biomarkers, such as magnetic resonance imaging, nuclear medicine techniques, and polysomnography. This multimodal approach enables progress in early diagnosis, patient stratification, and the prediction of clinical progression in Lewy body dementia, a pathology that is notably complex from a diagnostic standpoint.

In both cases, Institut de Recerca Sant Pau serves as the host institution for the grants, providing the institutional and scientific framework necessary for the development of the research activity. The incorporation of Dr. Víctor de la Peña Arteaga and Dr. Iñigo Rodríguez Baz strengthens IR Sant Pau’s commitment to the recruitment and consolidation of postdoctoral research talent. It also aims to advance research lines aligned with priority areas such as mental health and neurodegenerative diseases.

The awarding of these two Sara Borrell contracts adds to the set of competitive grants obtained by IR Sant Pau in the 2025 call. It reinforces its role as a reference environment for postdoctoral training and the development of high-quality biomedical research. This has the potential to advance scientific knowledge and improve patient care.

The Sant Pau Research Institute (IR Sant Pau) has been awarded three highly competitive grants from the Spanish State Research Agency (AEI), corresponding to two Ramón y Cajal contracts and one Juan de la Cierva contract. This recognition reflects the quality of the research carried out at the center and its ability to attract, foster, and project scientific talent. It also promotes the participation and leadership of women in science, a strategic priority that IR Sant Pau actively advances to move toward more diverse and inclusive research.

The Ramón y Cajal grants are aimed at researchers with an outstanding scientific track record. They make it possible both to recruit new profiles and to advance the careers of those already working at centers of excellence, fostering the development of independent lines of research. For their part, the Juan de la Cierva grants support postdoctoral specialization and strengthen the progression of early-career researchers within groups with strong training capacity.

In this context, IR Sant Pau welcomes Dr. Dora Koller through a Ramón y Cajal grant. Dr. Koller is an interdisciplinary researcher whose profile combines genomics, pharmacogenetics, precision medicine, and computational analysis. Her international career, which includes an extended period at Yale University (United States), has focused on identifying complex genetic relationships between physical conditions—such as endometriosis or chronic pain—and psychiatric disorders. She has an extensive national and international collaboration network and plays a prominent role as a lead analyst in major reference consortia, such as the Women’s Health Initiative and the Chronic Pain Genomics Consortium.

Dr. Koller has led pioneering studies that provide an integrated view of mental and physical health. Her expertise in pharmacogenetics platforms and advanced analytical methods represents a strategic boost for the development of new personalized medicine approaches at IR Sant Pau. Dr. Koller will join the Perinatal and Women’s Medicine Group, led by Dr. Elisa Llurba.

The second Ramón y Cajal grant has been awarded to Dr. Marta Cano Català, who was already conducting her scientific work at IR Sant Pau and who, through this grant, strengthens her career trajectory at the center. Dr. Cano is a recognized expert in neuroimaging applied to affective disorders, with a particular interest in the mechanisms of action of rapid-acting antidepressant treatments, such as electroconvulsive therapy (ECT).

Her research has made it possible to identify structural and functional biomarkers that improve understanding of therapeutic response, opening new avenues toward precision psychiatry. Her participation in international consortia such as GEMRIC and ENIGMA helps position IR Sant Pau as a reference center in the field of clinical neuroimaging. Dr. Cano will join the Mental Health Group, led by Dr. Maria J. Portella.

Meanwhile, the Juan de la Cierva grant has been awarded to Dr. Estela Rosell Mases, a new addition to the research group in Endocrinology, Diabetes, and Nutrition, led by Dr. Dídac Mauricio. This contract allows her to strengthen her scientific profile and contribute to a line of work with a strong translational component. Dr. Rosell’s research will focus on evaluating the role of molecules derived from the gut microbiota in metabolic-associated fatty liver disease in in vitro and in vivo experimental models and in human cohorts.

The awarding of these three grants underscores IR Sant Pau’s commitment to scientific excellence, personalized medicine, mental health, translational research, and the promotion of female talent in science. All the beneficiaries are early-career researchers who help strengthen the presence of women in traditionally underrepresented fields, a priority aspect of the center’s strategy to foster equal opportunities and ensure more competitive and equitable research. Through competitive programs such as those of the AEI, IR Sant Pau continues to reinforce its role within the biomedical ecosystem and to generate impactful knowledge to improve people’s health.

The Sant Pau Research Institute (IR Sant Pau) has been awarded a Juan Rodés contract from the Carlos III Health Institute (ISCIII). This is a national program aimed at consolidating the research careers of clinical professionals within the National Health System and facilitating the stable integration of research into the hospital setting.

The beneficiary of the contract is Dr. Carla Abdelnour Ruiz, a specialist in neurology, who will carry out her activity in the neurology department of Sant Pau Hospital. The contract, with a duration of four years, allows clinical care to be combined with sustained dedication to research, strengthening the hospital’s role as an environment for generating biomedical knowledge closely linked to patient care.

Dr. Abdelnour Ruiz carries out her clinical and scientific activity in the field of cognitive impairment and neurodegenerative diseases, with a specific focus on dementias and, in particular, dementia with Lewy bodies. Her research trajectory is framed within consolidated lines of the Neurology Department and IR Sant Pau, with participation in clinical and translational research projects focused on these conditions. She also participates in studies aimed at improving their clinical characterization and diagnostic approach.

The Juan Rodés program is specifically designed to promote the stabilization of attending physicians with a scientific vocation, allowing continuity in clinical careers that structurally integrate research into professional practice. Through this model, talent retention within the public system is promoted, and links between hospitals and health research institutes are strengthened.

In this case, IR Sant Pau acts as the applicant institution and Sant Pau Hospital as the host institution, ensuring a stable framework for the joint development of clinical care and clinical research activity in neurology. This structure facilitates the continuity of existing lines of research and their translation into the clinical setting.

The awarding of this Juan Rodés contract represents a new boost to IR Sant Pau’s strategy to promote stable clinician-researcher career paths. It reinforces the center’s commitment to research aimed at improving knowledge, diagnosis, and care in dementias and other neurodegenerative diseases.

The Sant Pau Research Institute (IR Sant Pau) has secured six Río Hortega 2025 contracts from the Instituto de Salud Carlos III (ISCIII), a program designed to consolidate the careers of healthcare professionals who combine clinical practice with biomedical research.

These two-year grants will allow specialists with healthcare training and research experience to devote a significant portion of their time to research in hospital settings, integrating clinical practice with the generation of new knowledge. They aim to promote continuity in scientific careers at post-training stages and to strengthen translational clinical research within the National Health System.

This achievement consolidates the role of IR Sant Pau as an environment of excellence for training clinically oriented professionals with a strong research vocation. It underscores its commitment to the promotion of talent and the transfer of knowledge into clinical practice.

The new grants cover a wide range of areas, from cardiovascular diseases to neurosciences and genomics, and will be carried out in collaboration with established researchers at IR Sant Pau who lead competitive projects in their respective fields.

In the cardiovascular area, Dr. Jesús Díaz Gutiérrez, who will collaborate with the team led by Dr. Gemma Vilahur, will focus his work on studying the inflammatory and metabolic mechanisms involved in myocardial injury and in the progression of atherothrombosis. His research aims to understand how inflammation and lipid metabolism contribute to the development of cardiovascular disease and to identify new strategies to anticipate complications in patients with coronary artery disease. By applying molecular biology techniques and analyzing different cardiac imaging modalities, the project seeks to contribute to the development of more precise and personalized prevention strategies.

In the field of neurology, Dr. Joan Miquel Fernández Vidal, who will collaborate with Dr. Sònia Benítez, will direct his research toward cerebrovascular disorders. Dr. Fernández Vidal will study the role of lipid and inflammatory biomarkers associated with the progression of carotid atherosclerotic plaque. The aim is to identify factors that determine the risk of ischemic stroke and its recurrence, as well as the occurrence of other cardiovascular events. His project will combine clinical studies and laboratory analyses in patient cohorts to improve prognostic prediction. His work seeks to optimize stroke risk stratification and to guide therapeutic decision-making in a common condition with a major public health impact.

Also within the field of neurology, Dr. Júlia Peris Subiza, who will collaborate with Dr. Olivia Belbin, and Dr. Sara Rubio Guerra, affiliated with the team led by Dr. Ignacio Illán-Gala, will promote projects focused on neurodegenerative diseases. Dr. Peris Subiza will orient her research toward the development of biomarkers to improve the diagnosis of mental disorders and neurodegenerative diseases and to assess treatment efficacy. Dr. Rubio Guerra, for her part, will focus her project on the clinical and biological characterization of frontotemporal dementia and amyotrophic lateral sclerosis (ALS), integrating neuroimaging techniques, analysis of proteins associated with neuronal damage, and longitudinal patient follow-up. Her research will help define biological subtypes of these conditions and improve diagnostic precision.

Also in the area of neurology, but with a stronger focus on omics tools, Dr. Franco Emanuel Appiani, in collaboration with Dr. Israel Fernández, will participate in projects exploring gene regulation mechanisms in neurological and metabolic diseases. Using large-scale genomic and proteomic techniques, his research will seek to identify key biological pathways and biomarkers with diagnostic or prognostic value. These studies will contribute to a more in-depth understanding of the molecular bases of various complex diseases and to building bridges between molecular biology and clinical practice.

Finally, in the field of neurosciences, Dr. Helena Codes Méndez will develop a project in collaboration among the neuromuscular, rheumatology, and multiple sclerosis units, under the coordination of Dr. Luis Querol. Trained as a rheumatologist, Dr. Codes will focus her research on the early detection and biomarker-based monitoring of neurological complications associated with systemic autoimmune diseases. The study aims to identify biological indicators that enable early recognition of nervous system involvement and monitoring of its progression, with the goal of improving diagnosis and clinical management of these patients. This is a cross-cutting project that integrates clinical and experimental knowledge and strengthens collaboration across different specialties in a field of growing clinical and research relevance.

Securing these Río Hortega contracts reinforces the role of IR Sant Pau as a reference environment for training and incorporating new generations of clinical professionals into research. The projects to be carried out under these grants reflect the center’s commitment to research aimed at improving the diagnosis, treatment, and prevention of diseases with a high public health impact.

The Sant Pau Research Institute (IR Sant Pau) has been awarded five Predoctoral Training Contracts in Health Research (PFIS) from the Carlos III Health Institute (ISCIII) under the 2025 call. These four-year contracts are among Spain’s main national instruments for promoting early-stage training of researchers in biomedical sciences and represent a key pathway for entry into the health research system.

The award of these four grants will enable new PhD candidates to pursue their doctoral theses in competitive projects led at IR Sant Pau. They will integrate into well-established research teams and contribute to advances in knowledge in areas of high clinical relevance. The PFIS program combines advanced methodological training, participation in ongoing studies, and mentoring during the early stages of a scientific career, reinforcing the institute’s commitment to emerging talent.

One of the new PhD candidates is Ainel Iskakova, who will carry out her research under the supervision of Dr. María José Martínez-Zapata. Her thesis is part of projects aimed at improving postoperative care through the use of innovative digital tools. Specifically, her work will focus on evaluating interventions that facilitate remote monitoring of patients after major cardiac surgery, with the goal of optimizing clinical management and helping to reduce complications and hospital readmissions. The analysis of different digital systems will make it possible to assess their impact on postoperative recovery and on the early detection of adverse events, ultimately supporting clinical decision-making and improving patient safety.

Also joining the institute is Montserrat Moncunill, who will develop her doctoral thesis under the supervision of Dr. Luis Prats Sánchez, with the collaboration of Dr. Sònia Benítez and Dr. Núria Puig, within a line of research focused on intracerebral hemorrhage. This type of stroke, one of the most severe, with a mortality rate of 40%, still lacks tools that allow accurate prediction of its clinical course. Her research will be integrated into projects that combine clinical, neuroimaging, and biomarker data to identify factors that may help anticipate hematoma progression and the risk of complications. The findings could contribute to improving early management of these patients and to fostering more personalized care based on noninvasive biomarkers.

In the field of mental health, Ariana Murillo will begin her predoctoral training under the supervision of Dr. Narcís Cardoner, Dr. Romina Miranda-Olivos, and Dr. Marta Cano, participating in research focused on the identification of potential biomarkers of response to rapid-acting antidepressants. Her thesis will explore the mechanisms of action of these therapeutic strategies through the integration of magnetic resonance imaging with syndromic and dimensional clinical assessments, with the aim of identifying individualized brain biomarkers that may optimize treatment personalization and advance toward precision psychiatry. This line of work is particularly relevant at a time when mental health research is moving toward more integrative models that combine clinical, neurobiological, and behavioral data to improve understanding and management of affective disorders.

For her part, Judit Selma González will carry out her doctoral thesis under the supervision of Dr. Ignacio Illán-Gala, within projects devoted to the study of neurodegenerative diseases. Her research will focus on evaluating the role of cognitive measures, together with emerging biomarkers, to gain a more in-depth understanding of the changes that occur in conditions such as Alzheimer’s disease and frontotemporal dementia. The use of advanced analytical techniques and the integration of clinical, cognitive, and biological information will make it possible to explore the evolution of these processes at early stages, contributing to improved early detection and to the identification of profiles with potential relevance for more targeted therapeutic strategies.

The fifth predoctoral grant has been awarded to Aya El Allam Kanice, who will carry out her doctoral thesis under the supervision of Dr. Mireia Tondo Colomer. Her research will focus on studying the role of high-density lipoprotein–mediated cholesterol transport (HDL) in the progression of Alzheimer’s disease in adults with Down syndrome. The project, which is part of the DOWNLIP study, combines analyses of plasma and cerebrospinal fluid biomarkers with longitudinal clinical and cognitive assessment, with the aim of identifying early indicators of cognitive decline and gaining a more profound understanding of the biological mechanisms linking lipid metabolism and neurodegeneration. The results could help improve early detection and open new opportunities for personalized medicine in a particularly vulnerable population.

The award of these five PFIS contracts reinforces IR Sant Pau’s commitment to the training of new scientific talent and the attraction of competitive funding. The PhD candidates will join an environment of excellence, where they will be able to build a solid research career and contribute to advances in biomedical research and improvements in patient health.

The choice of the drug used to induce sedation during emergency intubation in critically ill patients may have a meaningful impact on in-hospital survival. This is suggested by a recent study analyzing clinical outcomes associated with the use of etomidate and ketamine, two of the most commonly used agents for rapid sequence intubation in emergency departments.

The study, published in JAMA Network Open, is a multicenter investigation based on data from 18 hospitals in Brazil and was led by an international team of specialists in emergency medicine and critical care. The research included participation from the Sant Pau Research Institute (IR Sant Pau), through Dr. Otavio Ranzani, head of the DataHealth Lab at IR Sant Pau and senior coauthor of the article.

Differences in Mortality Associated With the Induction Agent

The study evaluated 1,810 critically ill adult patients who required emergency intubation and received either etomidate or ketamine as the sole induction agent. Using an advanced observational design that emulates a clinical trial, the investigators compared in-hospital mortality at 7 and 28 days after the procedure, adjusting results for multiple clinical and demographic variables.

The results show that patients who received etomidate had higher in-hospital mortality compared with those treated with ketamine. In the primary analysis, 28-day mortality was higher in the etomidate group, with a clinically meaningful absolute risk difference. This association remained consistent across multiple sensitivity analyses, reinforcing the robustness of the findings.

Regarding secondary outcomes, no significant differences were observed between the two groups in first-attempt intubation success or in most of the adverse events assessed. A higher frequency of early hemodynamic instability was observed in patients who received ketamine, a finding previously described and potentially related to the pharmacological properties of the drug and to patients’ clinical profiles.

Implications for Clinical Practice

Dr. Otavio Ranzani highlights the clinical relevance of the results: “Our data suggest that the choice of induction agent during emergency intubation is not a neutral decision and may influence outcomes as relevant as in-hospital survival. Although this is an observational study, the magnitude and consistency of the observed association justify further investigation into the impact of induction agents on clinical outcomes across different settings.” Dr. Ranzani adds, “This month, one of the largest clinical trials on this topic, the long-anticipated RSI trial, was published in The New England Journal of Medicine, showing neutral results regarding mortality but also raising questions about whether it had sufficient power to assess this outcome or whether its findings are applicable to settings beyond U.S. emergency departments and ICUs, where the trial was conducted.”

The authors emphasize that the study does not allow a definitive causal relationship to be established, but it does provide solid evidence to question the routine use of etomidate in critically ill patients. Particularly in a context in which widely available alternatives such as ketamine exist. In this regard, the work reinforces the need for continued research into how pharmacological decisions made in emergencies can have meaningful consequences for patient outcomes.

The participation of IR Sant Pau in this study reflects its commitment to clinical research aimed at improving the safety and outcomes of critically ill patients, as well as to generating high-impact scientific evidence that helps optimize clinical practice.

Reference Article:

Maia IWA, Decker SRR, Oliveira J E Silva L, von Hellmann R, Alencar JCG, Hajjar LA, de Carvalho JMD, Pedrollo DF, Nogueira CG, Figueiredo NMP, Miranda CH, Martins D, Baumgratz TD, Bergesch B, Colleoni O, Zanettini J, Freitas AP, Tambelli R, Costa MC, Correia W, de Maria RG, Filho UAV, Weber AP, da Silva Castro V, Dornelles CFD, Tabach BS, Moreira NP, Gaspar PL, Guimarães HP, Stanzani G, Gava TF, Mullan A, Brown CS, Bellolio F, Jeffery MM, Ranzani OT, Besen BAMP, Brazilian Airway Registry Cooperation (BARCO) group. Ketamine, etomidate, and mortality in emergency department intubations. JAMA Netw Open 2025;8:e2548060. https://doi.org/10.1001/jamanetworkopen.2025.48060

The Sant Pau Research Institute (IR Sant Pau) has led a multicenter project that redefines what is considered normal cognitive performance. The work, carried out in collaboration with Hospital Clínic de Barcelona, Hospital Universitario Marqués de Valdecilla in Santander, and the CITA-Alzheimer Foundation in San Sebastián, has resulted in two complementary scientific articles published in the journal Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM), which establish new cognitive reference standards based exclusively on individuals without amyloid pathology and demonstrate their ability to improve early diagnosis.

This initiative emerges at a pivotal moment for clinical practice. The arrival of disease-modifying therapies requires increasingly precise identification of patients who are in very early stages, when intervention is most effective and safest. However, traditional neuropsychology faces a fundamental challenge: determining what “normal performance” truly means in older adults, given that part of age-related decline can be confused with changes inherent to the preclinical phase of Alzheimer’s disease. The project addresses this need by redefining cognitive reference standards using advanced tools and data from rigorously selected populations, allowing for a more accurate delineation of the threshold between healthy aging and true cognitive decline.

New Reference Standards Based on Amyloid-Negative Individuals

In the first part of the project, neuropsychological reference standards based exclusively on individuals without Alzheimer’s disease biomarkers were developed for the first time, using advanced statistical models that take age, educational level, and sex into account. This combination, which until now had only been applied partially in certain specific tests, is used for the first time simultaneously and across such a broad battery of neuropsychological assessments, representing a significant methodological advance at the international level. This approach allows for a more precise definition of what can be considered truly normal cognitive performance in aging. By excluding individuals who already show amyloid pathology in the preclinical phase—still without symptoms—it prevents the mild decline associated with the disease from being mistaken for healthy aging.

The development of these new reference standards was based on a cohort of nearly 800 cognitively healthy adults and on advanced statistical models capable of describing in detail how age, education, and biological sex influence each cognitive domain. This approach made it possible to identify subtle but relevant differences between men and women, as well as nonlinear effects of age and education that previous methods could not detect, substantially increasing the precision of cognitive assessments.

In parallel, the team developed a clinical calculator that allows for rapid and accurate calculation of adjusted scores, facilitating individualized interpretation of each case in memory clinics. Although it is not intended for the public, the tool is designed so that all professionals who assess patients with suspected cognitive impairment can use it as diagnostic support, promoting consistent application of the new reference values in clinical practice.

As explained by Dr. Sara Rubio-Guerra, researcher in the Neurobiology of Dementias group, neurologist at the Sant Pau Memory Unit, and first author of the study, “a key part of diagnosis is clearly defining what we mean by cognitive normality. If this reference point is not accurate, we may overlook very early alterations or, conversely, raise concerns in completely healthy individuals. These new norms allow us to interpret performance more precisely and better distinguish between healthy aging and the earliest changes associated with the disease.”

The New Norms Enable Earlier Detection of the Earliest Cognitive Decline

In the second part of the study, an analysis was conducted in a sample of more than 2,400 individuals without dementia, demonstrating that application of these new reference standards substantially improves the ability to identify very mild cognitive alterations. The new standards make it possible to detect earlier one in five cases of incipient cognitive impairment that previously went unnoticed.

The data confirm that this group does not represent cognitive variability inherent to aging. These individuals show high rates of Alzheimer’s disease biomarkers and a faster cognitive decline in longitudinal analyses, indicating that they are indeed in an early stage of the disease. Earlier detection allows for more precise guidance of the diagnostic workup and helps determine when further evaluation with biomarkers is warranted.

By contrast, the number of individuals whom the new norms would classify as impaired in the absence of biological evidence of disease is small, around 3%, and in most of these cases biomarkers are negative. This minimizes the risk of overdiagnosis and avoids subjecting healthy individuals to unnecessary testing.

Earlier Diagnosis in the Era of Disease-Modifying Therapies

According to Dr. Ignacio Illán-Gala, researcher in the Neurobiology of Dementias group at IR Sant Pau, neurologist at the Sant Pau Memory Unit, and senior author of the study, “early diagnosis is key in the era of new disease-modifying therapies. Detecting these incipient cases earlier means being able to offer therapies at the time when they are most effective and safest.” The neurologist emphasizes that neuropsychology acts as “a gateway to the diagnostic workup,” especially when memory complaints are very subtle and the decision to request biomarkers requires knowing with precision whether true cognitive decline is present. “With more accurate reference values, we can better determine who needs further evaluation and who can be reassured, avoiding both overdiagnosis and missed therapeutic opportunities,” he adds.

Overall, the project consolidates IR Sant Pau’s leadership in the development of biomarkers and precision tools and lays the groundwork for future improvements as markers for other neurodegenerative diseases in preclinical stages are identified.

Reference Articles:

1. Rubio-Guerra S, Sánchez-Saudinós MB, Sala I, Videla L, Bejanin A, Estanga A, Ecay-Torres M, de Luis CL, Rami L, Tort-Merino A, Castellví M, Pozueta A, García-Martínez M, Gómez-Andrés D, Lage C, López-García S, Sánchez-Juan P, Balasa M, Lladó A, Altuna M, Tainta M, Arranz J, Zhu N, Alcolea D, Lleó A, Fortea J, Rodríguez ER, Sánchez-Valle R, Martínez-Lage P, Illán-Gala I. Development of amyloid-negative neuropsychological norms using GAMLSS. Alzheimers Dement (Amst) 2025;17. https://doi.org/10.1002/dad2.70224.
2. Rubio-Guerra S, Sala I, Sánchez-Saudinós MB, Videla L, Bejanin A, Estanga A, Ecay-Torres M, de Luis CL, Rami L, Tort-Merino A, Castellví M, Pozueta A, García-Martínez M, Gómez-Andrés D, Lage C, López-García S, Sánchez-Juan P, Balasa M, Lladó A, Altuna M, Tainta M, Arranz J, Zhu N, Alcolea D, Lleó A, Fortea J, Rodríguez ER, Sánchez-Valle R, Martínez-Lage P, Illán-Gala I. Amyloid-negative neuropsychological norms: Added value in the era of biomarkers and disease-modifying therapies. Alzheimers Dement (Amst) 2025;17. https://doi.org/10.1002/dad2.70223.

The Sant Pau Research Institute (IR Sant Pau) has been selected to participate in three high-impact scientific and technological projects funded through the 2024 Public-Private Collaboration Projects call from the Spanish State Research Agency (AEI), under the Ministry of Science, Innovation, and Universities. These grants, aimed at fostering the transfer of knowledge from research to the productive sector, represent a total funding of over €650,000 for the institute to develop new digital health tools. Innovative strategies for women’s health, and targeted cancer therapies based on nanotechnology.

The simultaneous award of these three projects places IR Sant Pau in a strategic position within translational research in Spain. This reinforces its role as a key scientific partner in public-private consortia that seek to transform laboratory advances into clinically applicable solutions.

ASISTE: Artificial Intelligence to Transform the Patient Experience in the Healthcare System

The project ASISTE – “Advancing Interactive and Technological Solutions for the User Experience,” coordinated by Digimevo in collaboration with Eurecat and IR Sant Pau, aims to make a qualitative leap in the relationship between patients and healthcare services. The consortium will develop an advanced virtual assistant based on artificial intelligence technologies, capable of providing personalized information, supporting decision-making, and integrating recommendations to improve therapeutic adherence and self-care.

Unlike conventional systems, ASISTE will explore multimodal and adaptive models that anticipate patients’ needs, reduce uncertainty, and optimize the flow of clinical information before, during, and after healthcare delivery. The project aligns with current trends in digital health, which emphasize patient empowerment and care efficiency.

The participation of IR Sant Pau, led by Dr. Elisa Llurba, will be essential to bring the technology into a real clinical environment. The institute will coordinate the pilot validation of the virtual assistant at Sant Pau Hospital, including methodological design, usability assessment, impact measurement in clinical practice, and evaluation of health outcomes. This work will draw on the experience and capabilities of the Clinical Research and Clinical Trials Unit (UICEC) Sant Pau and the Drug Research Center (CIM), essential infrastructures to ensure a safe and effective deployment in patients. The project has been granted €153,643.99 for IR Sant Pau.

OXO-001: A New Path to Modulate the Vaginal Microbiota and Improve Reproductive Health

The second funded project, Study and Development of a Strategy to Modulate the Vaginal Microbiota with the Compound OXO-001, led by the biotech company Oxolife, focuses on the compound OXO-001 and its ability to modulate the vaginal microbiota and correct dysbiosis. The conditions that can affect gynecological and reproductive health. The initiative, involving the University of Barcelona and IR Sant Pau, addresses an emerging and relevant clinical field in which the vaginal microbiota is increasingly recognized as a key determinant of fertility and reproductive success.

IR Sant Pau plays a central role in the project’s clinical phase, in which the safety and biological effects of OXO-001 will be studied in healthy female volunteers, analyzing how it modulates microbial balance and assessing its potential to open new therapeutic strategies in fertility and women’s health, with Dr. Rosa Antonijoan as principal investigator. A leading expert in clinical pharmacology and first-in-human trials, Dr. Antonijoan will head the planning, execution, and supervision of the clinical study, which will be conducted at the CIM Sant Pau facilities, a platform renowned for its expertise in early-phase studies, safety assessment, and rigorous data monitoring. The grant awarded to IR Sant Pau for this project amounts to €147,129.81.

NNL1524: A Next-Generation Nanodrug for Tumors Overexpressing CXCR4

The third project, Innovative Nanodrug Targeted to CXCR4+ Tumor Cells: Toward the First-in-Human Clinical Trials of a Revolutionary Therapy for Aggressive Cancers, coordinated by the company Nanoligent—a spin-off linked to the UAB and IR Sant Pau—represents an innovative approach in precision oncology. The Institute of Nanoscience and Materials of Aragon and the Margarita Salas Center for Biological Research, both part of the Spanish National Research Council (CSIC), will also participate in its development.

The goal is to advance the preclinical development of the nanodrug NNL1524, based on a disruptive protein-drug nanoconjugate technology capable of specifically targeting tumor cells that overexpress the CXCR4 receptor. This receptor is a pan-cancer biomarker associated with tumor aggressiveness, poor prognosis, metastasis, and therapeutic resistance.

NNL1524 combines a modular protein design, a high-affinity ligand, and a potent cytotoxic agent, resulting in small-sized, highly selective nanomedicines that maximize targeted drug delivery to enhance antitumor efficacy while minimizing toxicity in healthy tissues. The project includes producing the first non-GMP batch of the nanodrug, extended pharmacokinetic and metabolism studies, and consolidating the preclinical evidence required for a first-in-human clinical trial application.

IR Sant Pau’s role in this consortium is pivotal. Under the direction of Dr. Ramon Mangues, the institute will conduct an extensive series of animal model studies to evaluate the nanodrug’s efficacy compared with standard treatments, characterize CXCR4 expression levels predictive of therapeutic response, and assess whether combining it with immunotherapies—such as immune checkpoint inhibitors—enhances antitumor effects. These studies are essential to define the clinical positioning of NNL1524 and support the design of future human trials. The project has received over €2.5 million in total funding, of which €360,720.89 corresponds to IR Sant Pau.

Three Projects Driving IR Sant Pau’s Research Strategy

IR Sant Pau’s participation in these three AEI-funded projects strengthens its role as a center of excellence in translational biomedical research, capable of integrating fundamental science, technological innovation, clinical validation, and collaboration with the business sector. The institution provides consortia with a cutting-edge scientific ecosystem that includes the UICEC Sant Pau, CIM, Biobank, omics platforms, advanced imaging services, cytometry, microscopy, proteomics, and an animal experimentation service that enables complex in vivo studies.

Overall, the CPP2024 grants provide IR Sant Pau with €661,494.64 in competitive funding, supporting the development of innovative solutions with a direct impact on three priority areas for public health: digitalization of healthcare, women’s health promotion, and advancement of targeted cancer therapies.

The Sant Pau Research Institute (IR Sant Pau) has secured two competitive grants from the Strategic Plan for Health Research and Innovation (PERIS) 2022–2027, a program of the Department of Health of the Government of Catalonia designed to strengthen applied research within the Catalan healthcare system. This funding will enable progress in developing artificial intelligence tools aimed at improving diagnosis and clinical decision-making in two highly time-dependent medical emergencies: acute myocardial infarction and stroke. In total, IR Sant Pau has received 129,735 euros under the medical technology and digital health category.

The first funded project is RAPID-AIM, co-led by Dr. Matías E. Calandrelli, cardiologist at the Cardiology Department of Hospital de Sant Pau, specialized in cardiac imaging and the application of digital technologies to clinical practice, together with Dr. Martín Descalzo, coordinator of Cardiac MRI in the Cardiac Imaging and Function Unit. They will develop an autonomous clinical agent capable of interpreting electrocardiograms from a simple photograph taken with a mobile phone. This approach makes it possible to identify different types of heart attacks without requiring digitized ECGs or advanced IT systems, making it a particularly valuable solution for regional hospitals, resource-limited emergency departments, or situations in which no cardiologist is available. The project plans the progressive integration of this tool into the clinical workflows of Hospital de Sant Pau and the execution of a prospective study to assess its real-world clinical impact, with a view to future certification as medical software.

According to Dr. Calandrelli, the project’s transformative potential is clear. “Our goal is for any professional, in any setting, to have immediate access to a second opinion powered by artificial intelligence. Every minute gained during a heart attack means saving heart muscle and saving lives.” The researcher also highlights RAPID-AIM’s innovative element, noting that it “works directly with ECG images, making it universally applicable even in settings without advanced digital systems.”

The second funded project, RACE+BIO, is led by Dr. Natalia Pérez de la Ossa, a vascular neurologist at Hospital de Sant Pau and an international reference in prehospital stroke care, author of the RACE scale, and principal investigator of the RACECAT study. The project builds upon the development and refinement of the RACE+ tool, a predictive algorithm powered by artificial intelligence that can accurately predict the main stroke subtypes, particularly large-vessel occlusion, and guide early decisions on the patient’s hospital destination. This can reduce critical delays and increase access to advanced therapies. The development includes, on the one hand, validating the RACE+ tool across diverse international healthcare ecosystems and, on the other, combining it with point-of-care blood biomarkers—rapid, portable tests that can be performed directly in the ambulance and deliver results within minutes without requiring a laboratory.

For Dr. Pérez de la Ossa, this technology represents a significant advancement in urgent stroke care. “RACE+BIO will allow us to know, from the ambulance and in under ten minutes, what type of stroke the patient has—information that is essential to deciding which hospital they should be taken to based on therapeutic needs. This information is critical because a two-hour delay can reduce the chances of recovery by 10%,” she explains. The researcher also stresses the project’s broader potential: “If we succeed in integrating artificial intelligence and biomarkers into prehospital triage, we will transform how emergency systems make decisions, particularly in rural areas or locations far from tertiary centers.”

Both projects share common goals, such as reducing inequity, optimizing healthcare system resources, and improving clinical outcomes in time-dependent conditions. The integration of digital tools powered by artificial intelligence will shorten critical delays, avoid unnecessary transfers, strengthen coordination between the Medical Emergency System (SEM) and hospitals, and support professionals acting during the first minutes of cardiovascular or neurological emergencies.

The awarding of these PERIS grants by the Department of Health reinforces IR Sant Pau’s leadership in digital health and reaffirms its commitment to translational research focused on solving real-world clinical challenges. RAPID-AIM and RACE+BIO represent a step forward in incorporating artificial intelligence into the Catalan healthcare system and pave the way for new diagnostic tools that could be integrated into emergency services in the near future, contributing to more equitable, efficient, and evidence-based care.

A research team led by Dr. Àlex Bayés, Head of the Molecular Physiology of the Synapse Group at the Institut de Recerca Sant Pau (IR Sant Pau), has achieved what for decades had been an elusive goal: obtaining a precise, differentiated molecular portrait of individual synaptic types in the hippocampus, the brain structure that serves as the core of learning and memory.

The study, published in Nature Communications and conducted almost entirely at IR Sant Pau, details with unprecedented resolution which proteins are present in each type of synapse and in what quantities. This reveals patterns that help explain how connections that appear similar can perform different functions and display specific characteristics. Understanding how these connections are altered is critical because synaptic dysfunction is implicated in most neurological and psychiatric diseases, from Alzheimer’s and Parkinson’s to epilepsy and schizophrenia.

Synapses, the contact points between neurons, are extremely numerous and diverse: the human brain is estimated to contain between 100 and 1,000 trillion of them. Each one transmits information with slight variations in structure and function, allowing neural circuits to process signals flexibly and precisely. However, until now it was unknown how this diversity was reflected at the molecular level. “For years, scientists have known that each type of synapse has unique electrical properties, but they had not been able to map their protein composition accurately due to technical limitations,” explains Dr. Bayés. “Available methods required analyzing large tissue fragments that mixed different classes of connections, producing an average profile that blurred subtle yet critical differences for their function.”

A Technical Challenge Solved Through Methodological Innovation

Studying synapses individually has been an almost impossible challenge for decades. They are tiny structures—barely one micron—distributed densely and interwoven throughout the brain, making physical isolation difficult. Moreover, their number is so colossal that, if each synapse were a grain of sand, there would be enough to fill half a stadium like Camp Nou, an image that illustrates the magnitude of the challenge facing neuroscience.

The IR Sant Pau team has overcome this obstacle through a combination of tools that take synaptic analysis to a new level. Laser-capture microdissection makes it possible to precisely isolate microscopic hippocampal layers, selecting only those regions containing the synapse type of interest. Then, an optimized protocol for extracting synaptic proteins preserves the integrity of these molecules and prevents losses, which is crucial when working with minuscule amounts of material.

Thanks to this approach, the researchers were able to characterize individually the proteome of the three synapse types that make up the trisynaptic hippocampal circuit, perhaps the most extensively studied circuit in the brain. It is a characteristic network that transmits information in three steps: first from the entorhinal cortex to the dentate gyrus, then from the dentate gyrus to the CA3 region, and finally from CA3 to CA1. This circuit is essential for memory processing and the integration of sensory and contextual information.

The importance of this achievement is not only technical. “Because we can examine specific synapses without requiring genetic manipulation, the methodology can also be applied to human samples, opening a range of possibilities for precisely studying how these connections are altered in neurological diseases,” notes Dr. Bayés.

The Same Menu, Served Differently

The study revealed a surprising pattern: the three synapses analyzed share the vast majority of their proteins but vary significantly in the relative quantities of each. The comparison can be understood as if all of them used the same basic ingredients for cooking but modified the proportions to create different recipes with their nuances in flavor, texture, and properties.

In this “synaptic menu,” there is one ingredient always present that defines the character of the dish: glutamate receptors and the proteins that regulate them. Glutamate is the main excitatory neurotransmitter in the brain, and its receptors are essential for signal transmission and synaptic plasticity—the mechanism that allows connections to strengthen or weaken depending on experience.

“We observed that the functional identity of each synapse is not built on an exclusive set of proteins, but rather on how it adjusts the proportion of shared components to meet its needs,” says Dr. Àlex Bayés, “and what is most surprising is that, in all cases, glutamate receptors and their regulators form the core of that specialization.”

Three Molecular Profiles With Specific Functions

Quantitative differences in protein composition translate into specialized functional profiles. CA3–CA1 synapses display very precise control of a specific AMPA receptor subtype (GluA2), a high capacity to remodel their structure, and elevated energy consumption, all of which are associated with their role in memory consolidation and long-term plasticity.

DG–CA3 synapses stand out for their high abundance of metabotropic glutamate receptors (mGluR1) and for possessing especially active machinery for local protein synthesis in their presynaptic terminals. This feature allows them to adapt rapidly to changes in neuronal activity.

Meanwhile, EC–DG synapses present a distinct extracellular matrix, rich in proteoglycans, which may influence the mobility and stability of receptors, as well as specialized metabolic pathways to obtain energy from specific amino acids. These traits may relate to their role in the first stage of processing the information reaching the hippocampus.

The Role of Genetic Regulation

The study also identified a genetic component in this specialization: each neuron type activates or silences specific synaptic genes to adjust the molecular composition of its connections. This differential regulation was observed especially in genes related to glutamate receptors and the proteins that modulate their function, confirming that their central role in synaptic specialization is also encoded in the neuron’s genetic program.

“This is the first time we can link the molecular specialization of a synapse so directly to gene expression programs unique to each neuron. This brings us closer to understanding how synaptic diversity translates into unique functions for each brain circuit,” adds Dr. Bayés.

Implications and Next Steps

The ability to analyze the molecular identity of specific synapses with such precision not only in animal models but also in human tissue opens a range of applications in biomedical research. The hippocampus is one of the first structures affected in neurodegenerative diseases such as Alzheimer’s, so understanding how these “molecular recipes” are altered could help identify early biomarkers and develop more specific therapeutic strategies.

Reference Article:

Reig-Viader R, Del Castillo-Berges D, Burgas-Pau A, Arco-Alonso D, Zerpa-Rios O, Ramos-Vicente D, Picañol J, Castellanos A, Soto D, Roher N, Sindreu C, Bayés À. Synaptic proteome diversity is shaped by the levels of glutamate receptors and their regulatory proteins. Nat Commun 2025;16:10487. https://doi.org/10.1038/s41467-025-65490-9

The Sant Pau Research Institute (IR Sant Pau) has appointed David González Gil as its new general manager, a nomination approved by the Foundation’s Board of Trustees at its extraordinary session on October 6. David González officially took office on December 9, with the aim of driving a new phase of growth and consolidation for the center.

With more than twenty years of experience in managing research institutions, universities, and internationally oriented foundations, the new general manager joins IR Sant Pau with a strong profile in strategic leadership, resource mobilization, and organizational sustainability. Over the course of his career, he has led multidisciplinary teams and contributed to strengthening the competitiveness and visibility of a range of scientific and academic institutions.

Before joining IR Sant Pau, he served as general manager of the National Center for Genomic Analysis (CNAG), where he oversaw the establishment and consolidation of this scientific infrastructure of reference in genome research. This infrastructure was created through the partial spin-off of the Center for Genomic Regulation (CRG). Previously, he held the general manager position at the Pontifical University of Salamanca as a member of the rector’s office and chief executive of the leadership team, promoting the new strategic plan and the institution’s repositioning. He also held senior leadership roles at La Salle–Ramon Llull University, contributing to its global growth.

David González holds a Bachelor’s Degree in Economics from the University of Barcelona and has completed executive education programs at IESE, Harvard Business School, EADA, Aston University, and La Salle. He is currently a doctoral candidate in Economics and Law at the International University of Catalonia.

Upon his appointment, the new general manager expressed his satisfaction with joining the IR Sant Pau project, noting that “it is an honor to join an institute distinguished by its talent, commitment, and scientific contribution. My goal is to strengthen the conditions that will allow us to continue generating excellent research and maximize its impact on health and society.”

Regarding his appointment, IR Sant Pau highlights that the new general manager brings a combination of strategic vision, management experience, and driving capacity that will be key to advancing the institute’s objectives for growth, competitiveness, and scientific impact.

With this new chapter, IR Sant Pau also expresses its gratitude for the work and dedication of Jaume Bacardit, who has served as the institution’s general manager for the past three years.