Unidad de Investigación

Physical Activity, Children and Youth

Physical Activity, Children and Youth

Effect of physical activity and exercise on the physical and mental health of both healthy and clinical pediatric population.

Investigador principal
Equipo de investigadores
Área de investigación
Active and healthy life
The impact of physical activity in young people
Actualidad

Experts gathered at UPNA urge health professionals to prescribe physical activity for the prevention of chronic disease

Author
UPNA

Experts gathered at the Public University of Navarra (UPNA) have urged health and sports professionals to become ‘health agents’ by promoting physical activity among young people and pregnant women. Their goal is to improve the health and fitness of the population as a strategy to prevent non-communicable chronic diseases like obesity, heart disease or type 2 diabetes. A symposium was held by UPNA in Pamplona on Thursday 9 May to discuss exercise prescription as a way to improve health in all ages. Organised by the School of Medical Sciences and the Department of Medical Sciences, the event drew some 130 sports, health and biomedical experts.

Two UPNA researchers, who are also members of Navarrabiomed (the joint biomedical research centre of the Government of Navarra and the Public University of Navarra) and the Navarra Medical Research Institute (IdiSNA), delivered speeches: Mikel Izquierdo Redín, organiser the event, and Robinson Ramírez-Vélez. Mikel Izquierdo talked about strength training and the functions of the muscular system, ‘which a number of health professionals consider important for improving health and recovering from diseases linked with a sedentary lifestyle and population ageing, as well as for optimising sport performance after muscle injury.’ He debunked some of the myths created by pseudo-therapies in connection with strength training and improved muscle function. He said that muscle loss is not an inevitable outcome of ageing, as it can be prevented with proper training. He also observed that it is not true that children cannot do strength training exercises; on the contrary, they can, as long as they engage in controlled movements that are suitable for their age. He insisted that fitness ‘always’ offers benefits to patients who suffer from diseases such as type 2 diabetes and denied that the best muscle training is the one associated with extreme fatigue.

Finally, Izquierdo questioned the effectiveness and validity of the Kinesio Taping Method (which consists in applying elastic strips on muscles to treat pain), hypopressive techniques, electro stimulation suits and muscle roller sticks.

Health and pregnancy

Robinson Ramírez-Vélez said that, despite the efforts made to prevent non-communicable chronic disease, such as promoting healthy habits like physical exercise, a balanced diet, a good night’s sleep, quitting smoking and drinking, and so on, ‘we have failed to obtain the desired results.’ Studies reveal, he added, that ‘the mother’s state of health during pregnancy conditions to some extent the developing baby’s health later in life.’ He highlighted the importance of physical activity in children and adolescents – both aerobic exercise and resistance/strength training. Also, he insisted that health professionals should prescribe physical activity in all stages of life, even pregnancy.

The closing lecture was delivered by Antonio García-Hermoso, of Navarrabiomed and IdiSNA. He showed his disappointment in the fact that ‘Physical Education in school is not considered to be as important as subjects.’ He cited important international studies concluding that ‘exercise in youth is good for both physical and mental wellbeing.’ Finally, García-Hermoso recommended that ‘sports should be given the importance they deserve in primary, secondary and higher education.’

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Antonio García-Hermoso, Mikel Izquierdo and Robinson Ramírez.
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Functional training space
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Contacto
Physical Activity, Children and Youth

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Microbial Pathogenesis

Microbial Pathogenesis

The objective of the Microbial Pathogenesis Research Unit is to understand, at the molecular level, how pathogenic bacteria grow adhered to the surface of medical devices or tissues, producing infections that do not respond to antibiotic treatment and therefore often become chronic. To study this form of bacterial growth, which is called biofilm, the group employs genetic engineering approaches, omics technologies, synthetic biology and animal experimentation models. The ultimate aim of their research is to identify the critical elements of the biofilm formation process in order to prevent its formation, eliminate already formed biofilms, improve existing treatments or promote the formation of biofilms of non-pathogenic bacteria for therapeutic purposes.

Research lines:
•    Signal transduction mechanisms in bacteria.
Development of bacteria for therapeutic purposes and identification of new targets for the treatment of infections.
•    Study of bacterial adhesion to abiotic surfaces, such as medical implants and tissues.
 

Investigador principal
Área de investigación
Immune & infectious inflammatory diseases
Favouring the formation of non-pathogenic bacteria biofilm for therapeutic purposes
Actualidad

Microbial Pathogenesis Unit of Navarrabiomed-UPNA identifies new gene structure in bacteria that may trigger novel developments in the fields of synthetic biology and bacterial biotechnology

Author
Navarrabiomed

The Microbial Pathogenesis Unit of Navarrabiomed-Public University of Navarra (UPNA) has found a new genetic organisation in bacteria that helps better understand bacterial biology. The study of this genetic architecture was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Research background

In 1961, François Jacob and Jacques Monod discovered that bacteria group the genes that encode the proteins for a certain metabolic pathway in a single transcription unit (which they called ‘operon’). They won the Nobel Prize in Physiology or Medicine in 1965 for their discovery.

The bacteria they chose for their study was Escherichia coli, which normally lives in the intestines of healthy people; specifically, they studied the set of genes E. coli bacteria need to transport lactose (milk sugar) and break it down. E. coli only produces the three proteins it needs to digest lactose when the sugar is available. To simplify transcription regulation, the three genes involved are adjacent in the genome and under a single regulation system. Similar transcriptional regulation systems are found in other metabolic pathways in all bacteria.

Research at Navarrabiomed

In 2018, the team of researchers at Navarrabiomed coordinated by Iñigo Lasa Uzcudun, Head of the Microbial Pathogenesis Unit and Director of the biomedical research centre, described a new way genes are organised in bacteria. This regulation system has a higher level of regulation in operon structure, which the authors of the study named ‘non-contiguous operon’.

The bacterial model analysed has a group of four genes that are transcribed as a transcription unit despite the existence of a separate gene between the second and third genes that is transcribed in the opposite direction.

This transcriptional architecture results in an antisense transcript that acts as a mutual regulation system for the expression of the genes in the operon and the gene that produces this antisense transcript. Therefore, the concept of non-contiguous operon includes not only the genes transcribed from the same transcription unit but also overlapping genes whose expression is coordinated with that of the genes in the operon.

This finding deepens the understanding of bacterial biology and may trigger novel developments in the fields of synthetic biology and bacterial biotechnology.
The study was carried out as part of the scientific activity done at the Navarra Medical Research Institute (IdiSNA).

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Navarrabiomed y la UPNA caracterizan el sistema sensorial de las bacterias para el desarrollo de antibióticos más eficaces

Author
Navarrabiomed
  • El estudio, financiado por el Ministerio de Economía, ha sido publicado por la prestigiosa revista Nature Communication.

Un equipo científico del centro de investigación biomédica Navarrabiomed -centro mixto del Gobierno de Navarra y la Universidad Pública de Navarra (UPNA)- ha conseguido caracterizar el sistema sensorial que las bacterias utilizan entre otras cosas para multiplicarse en el cuerpo humano y causar infección.

El avance, que ha sido publicado por la revista científica Nature Communications y cuenta con financiación del Ministerio de Economía, Industria y Competitividad, permite comprender mejor cómo las bacterias se adaptan a las diferentes condiciones ambientales y posibilitará el desarrollo de antibióticos más específicos y eficaces.
El estudio ha contado con el liderazgo del doctor Iñigo Lasa, director de Navarrabiomed e investigador responsable del Grupo de Patogénesis Microbiana del centro. Asimismo, han colaborado investigadores del Instituto de Agrobiotecnología (UPNA-CSIC-Gobierno de Navarra), del Instituto de Biomedicina de Valencia (CSIC) y del Institute of Infection, Immunity and Inflammation, University of Glasgow.

Bacterias superresistentes

Actualmente, la aparición de bacterias farmacorresistentes, que no responden a tratamientos con antibióticos, constituye uno de los problemas sanitarios a escala mundial priorizados por la Organización Mundial de la Salud (OMS).

Las bacterias detectan, responden y se adaptan a los cambios en su entorno utilizando unos elementos sensoriales denominados sistemas de dos componentes. Este tipo de sistemas sensoriales están presentes en bacterias, hongos y plantas, pero no se encuentran en células animales. En el caso de las bacterias, regulan procesos celulares tan importantes como la virulencia o su propio crecimiento, lo que los convierte en dianas para el diseño de nuevas terapias antimicrobianas.

El objetivo del trabajo ha consistido en eliminar todos los sistemas de dos componentes, es decir el sistema sensorial completo, en Staphylococcus aureus, uno de los principales patógenos humanos según la OMS y, posteriormente, en la generación de una colección de bacterias cada una de las cuales contiene un único sistema de dos-componentes. Esta estrategia ha permitido simplificar una compleja red sensorial en cada uno de sus elementos para comprender cuál es la función individual de cada uno de los sistemas y la relación existente entre ellos. 

Aplicación clínica de la investigación

En relación a la aplicación clínica, Iñigo Lasa apunta al desarrollo de nuevos antibióticos más específicos. “El hecho de que los sistemas de dos componentes estén presentes en todas las bacterias patógenas y no en las células de nuestro organismo nos puede permitir desarrollar fármacos que bloqueen estos sistemas, evitando así el desarrollo de la bacteria durante la infección, sin causar ningún efecto secundario sobre nuestras células”.

En este sentido, las bacterias generadas en este estudio han sido patentadas y actualmente el equipo analiza diversos compuestos marinos que puedan incorporarse en el tratamiento y control de infecciones en la práctica clínica.

La investigación forma parte de la actividad científica del Instituto de Investigación Sanitaria de Navarra (IdiSNA), agrupación público-privada para el fomento de la investigación biomédica en la Comunidad Foral y de la que son miembros Navarrabiomed y la UPNA.

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Microbial Pathogenesis
Lab
Colaboradores/as
Dr. Maria de Toro
CIBIR
Dr. Miriam García
Instituto de Investigaciones marinas (VIGO)
Dr. Andreas Haag
University of St. Andrews
Dr. Andre Mateus
Umea University
Prof. Silke Leimkuehler
Universität Potsdam
Prof. José Penades
Imperial College
Dr. Jerónimo Rodríguez
Ramón y Cajal Health Research Institute (IRYCIS)
Prof. Nassos Typas
EMBL
Dr. Nina M. van Sorge
University of Gottemburg
Unidad de investigación / Grupo Vinculado
Contacto
Microbial Pathogenesis

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Gastroenterology

Gastroenterology

Research unit formed by members of the Digestive Service of the University Hospital of Navarra and Navarrabiomed researchers, whose aim is research on various pathologies affecting the digestive system with the goal of improving diagnosis, developing new treatment techniques and optimizing already established endoscopic techniques, all with the ultimate goal of its clinical application.


Lines of research:


•    Treatment of premalignant lesions and early neoplasms of the digestive tract.

•    Search for new endoscopic and molecular tools for the early detection of gastric cancer.
•    Treatment of esophago-gastric motor disorders.
•    Liver diseases.
•    Diagnosis and management of pancreatic diseases.
•    Diagnosis and management of biliary pathology.
•    Biliopancreatic oncology.
•    Neurogastroenterology.
•    Eosinophilic esophagitis.
•    Diagnosis and treatment of inflammatory bowel disease.
•    Gastrointestinal bleeding.
•    Therapeutic endoscopy research.
•    Familial and hereditary cancer.
 

Investigador principal
Equipo de investigadores
Área de investigación
Digestive
Research and development of new therapeutic endoscopy techniques
Actualidad

‘la Caixa’ Foundation, Caja Navarra Foundation and Navarrabiomed launch programme to foster public biomedical research in Navarra

Presentación de las líneas de negocio
Author
Navarrabiomed
  • The programme will offer support to the development of studies in digestive medicine, geriatrics, neuroscience and oncology that will bring advancement and excellence in these fields of research.
  • ‘la Caixa’ Foundation and Caja Navarra Foundation are channelling 1.2 million Euro into this programme, to be run by the biomedical research centre Navarrabiomed, where four doctors from the Navarra Health System-Osasunbidea (SNS-O) will carry out quality biomedical research studies.
  • Through this programme, ‘la Caixa’ Foundation and Caja Navarra Foundation will give support to the leading research centres in Navarra during the 2017-2021 period. Universities and research centres will thus get a total 6.4 million Euro.

Ana Díez Fontana, Regional Director of CaixaBank in Navarra; Javier Miranda, Chairman of Caja Navarra Foundation; and Iñigo Lasa, Director of Navarrabiomed, announced the research lines to be developed by doctors Eduardo Albéniz Arbizu, Nicolás Martínez Velilla, Maite Mendióroz Iriarte and Antonio Viudez Berral, who were selected by an external evaluation committee from 12 candidates.

The specialists in the programme will be relieved from part of their medical activity so that they can do research. They need time to develop their scientific projects and produce new knowledge in their medical specialties. The initiative enables the establishment of a critical mass of professionals that combine medical activity with research jobs, thus promoting translational medicine to the benefit of patients and society as a whole.

The four doctors selected to join the programme will soon start working at the labs of Navarrabiomed – the joint biomedical research centre of the Government of Navarra and the Public University of Navarra (UPNA). They will establish separate research units for the development of their projects, based on clinical practice at the Navarra Hospital Complex (CHN), with support from other Navarrabiomed units and platforms.

In addition to streamlining research activities in the respective units, they will encourage the participation of resident medical interns (MIRs) by getting them involved in biomedical research projects, trials and programmes.

Four excellent research projects in digestive medicine, geriatrics, neuroscience and oncology

Eduardo Albéniz Arbizu has worked in a number of hospitals across Spain. He received training in advanced endoscopy in France, Japan and China. Currently, he is working at the Gastrointestinal Endoscopy Unit of the CHN Digestive Medicine Service.

Dr Albéniz specialises in endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for the removal of early-stage gastrointestinal tumours. These advanced procedures reduce the number of surgical and other more invasive interventions in the treatment of superficial neoplastic lesions. Resection of colorectal polyps, for example, is the procedure with the highest survival rates observed in screening studies for colorectal cancer carried out in Navarra.
The goal of the project led by Dr Albéniz is to provide evidence for the identification of predicting factors for the effectiveness of resection procedures and other factors associated with potential complications that might be minimised.

Nicolás Martínez Velilla has been the Head of the Geriatrics Unit at CHN since 2015. In 2013, he was appointed head of a team partnered with Navarrabiomed for the promotion of research into different aspects of geriatric medicine.

Dr Martínez Velilla’s proposal includes a thorough study for the prevention of old-age frailty and disability or dependency in hospitals and in the community at large. Furthermore, it includes the creation of a European cross-border network to deal with various aspects of ageing. The project is aimed at rethinking hospitalisation of older adults, prescribing exercise to older patients in hospitals so as to improve their quality of life and increasing the sustainability of the health system.

Maite Mendióroz Iriarte has built her professional career as a doctor and researcher in Pamplona, Barcelona, San Sebastián and New York. Since 2010, she has been a member of the Neurology Department at CHN. Over the past few years, she has received grants from ‘la Caixa’ Foundation, Caja Navarra Foundation and the Government of Navarra to boost activity in the Neuroepigenetics Unit at Navarrabiomed.

Between 2018 and 2021, Mendióroz Iriarte will develop a project whose goal is to identify a potential blood-based epigenetic biomarker for early detection and treatment of Alzheimer’s disease. Her study might become the first step towards the implementation of precision medicine in neurodegenerative diseases.

Antonio Viudez Berral has developed his professional career in Navarra, Catalonia and Baltimore, USA. In 2010, he joined the Medical Oncology Service at CHN. Since then, he has been a researcher at Navarrabiomed as well.

Dr Viudez’s project will study pancreatic neuroendocrine tumours to find accurate markers that predict the effectiveness of certain therapies.

In addition, the Medical Oncology Service will be able to strengthen its scientific activity, establishing new lines of research for the improvement of diagnosis, prognosis and prediction of treatment response and toxicity.

From left to right: Luis Gabilondo, Ana Díez, Maite Mendióroz, Eduardo Albéniz, Antonio Viudez, Nicolás Martínez, Javier Miranda and Iñigo Lasa.

 

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Press conference.
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Press conference.
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Luis Gabilondo, Ana Díez, Maite Mendióroz, Eduardo Albéniz, Antonio Viudez, Nicolás Martínez, Javier Miranda and Iñigo Lasa.
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Entrevista con motivo del premio “Nuevas ideas de negocio en el ámbito de la salud 2021”
Eduardo
Albéniz Arbizu
Head of the Unit
Colaboradores/as
Vila Costas, Juan José
Co-Responsable. Complejo Hospitalario de Navarra
Bolado Concejo, Federico
Hospital Universitario de Navarra
Carrascosa Gil, Juan
Complejo Hospitalario de Navarra
Estremera Arévalo, Fermin
Complejo Hospitalario de Navarra
Fernández-Urien Sainz, Ignacio
Complejo Hospitalario de Navarra
Gómez Alonso, Marta
Complejo Hospitalario de Navarra
Uribarri González, Laura
Complejo Hospitalario de Navarra
Urman Fernández, Jesús María
Complejo Hospitalario de Navarra
Unidad de investigación / Grupo Vinculado
Contacto
Gastrointestinal Endoscopy

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Artificial Intelligence and Approximate Reasoning

Artificial Intelligence and Approximate Reasoning

The Group for Artificial Intelligence and Approximate Reasoning (GIARA) was founded in 2002 by Humberto Bustince, Chair Professor at the Public University of Navarre. GIARA is a multidisciplinary team (physicists, mathematicians, computer engineers and industrial engineers) that has a strong track record and a career with notable national and international impact. Its work focuses on the theoretical study of information fusion, the handling of uncertainty and fuzzy sets and their extensions, as well as on the development of models and applications in the fields of Data Mining, Big Data and Image Processing Deep Learning and Computational Neuroscience, among others.

Research lines:

  • Theory: information fusion, fuzzy sets and their extensions
  • Decision Making: multi-criteria, consensus, preference relations, recommendation systems
  • Computer Vision: image processing, magnification/reduction, edge detection, stereo vision
  • Machine learning: machine learning, classification, models based on fuzzy rules, models based on ensembles, Deep Learning, Big Data
     
Investigador principal
Área de investigación
Big Data & Bioengineering
Group GIARA
Colaboradores/as
De Miguel Turullols, Laura
Navarrabiomed - Universidad Pública de Navarrra
Fernández Fernández, Francisco Javier
Navarrabiomed - Universidad Pública de Navarrra
Guerra Errea, Carlos
Navarrabiomed - Universidad Pública de Navarrra
López Molina, Carlos
Navarrabiomed - Universidad Pública de Navarrra
Marco Detchart, Cedric
Navarrabiomed - Universidad Pública de Navarrra
Unidad de investigación / Grupo Vinculado
Contacto
Artificial Intelligence and Probabilistic Reasoning

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Exercise, Health, Metabolism and Functional Capacity

Physical Activity, Ageing and Fragility (CIBER)

The unit focuses on studying the effects of physical exercise throughout the lifespan, with a strong interest in populations ranging from children to older adults. We focus on a wide range of conditions, including obesity, diabetes, chronic obstructive pulmonary disease (COPD), heart failure, and mental health, analyzing how exercise can influence their prevention and treatment. In addition, we explore healthy aging, frailty, cognitive decline, and fall risk, seeking strategies to improve quality of life and promote well-being during these life stages. Our goal is to generate robust scientific knowledge that supports exercise-based interventions, thereby contributing to the health and well-being of the population.

Research lines:

  • Frailty and functional indicators related to aging
  • Biomechanics and the neuromuscular system of movement
  • Physical exercise and sedentary lifestyle-associated diseases: Diabetes, Obesity, COPD, and Cardiovascular Risk
  • Strength training and cardiovascular endurance: Neuromuscular, cardiovascular, and metabolic adaptations
  • Aging, cognitive decline, and physical activity: Assessment of balance, gait, and muscle power. Effects of exercise.
Investigador principal
Área de investigación
Active and healthy life
Healthy ageing, frailty, cognitive decline and fall risk
Actualidad

A study by the UPNA and Navarrabiomed indicates that increasing the intensity and quality of physical education classes improves students’ health

Author
UPNA
  • JAMA Pediatrics, the journal of the American Pediatrics Association, has published the study results.

A group of researchers from Navarrabiomed and the Department of Health Sciences at the Universidad Pública de Navarra (UPNA) specializing in prescribing physical exercise to improve health and quality of life has published an article on the effects of increasing the quality and quantity of physical education (PE) classes on improving the health-related physical fitness and fundamental motor skills of young people (ages 3 to 18). The article was recently published in JAMA Pediatrics (Journal of the American Medical Association).

The study analyzed data from approximately 50,000 young people and concluded that qualitative strategies such as including games and activities involving a high level of cardiovascular and muscular work, as well as better methodological session planning could provide young people with healthy benefits in terms of fitness and fundamental motor skills.

In addition to Antonio García-Hermoso, Robinson Ramírez-Vélez, Alicia María Alonso-Martínez and Mikel Izquierdo Redín (who form part of Navarrabiomed, Idisna and UPNA), the article authors also include Miguel Ángel Pérez-Sousa (Universidad de Huelva) and Rodrigo Ramírez-Campillo (Universidad de Los Lagos, Osorno, Chile).

Exercise is necessary to improve physical fitness

The study researchers also point out that it is not always possible to increase the number of hours spent per week on exercise or PE classes during school hours and therefore recommend improving the efficiency of these sessions by using strategies such as high-intensity interval training (HIIT), and muscle strength, jumping or circuit training. However, the authors mention that, despite the benefits of these strategies during school hours, young people should also participate in more out-of-school physical activities based on their age group (i.e., 60 minutes a day of moderate to intense physical activity).


They argue that PE classes also offer other benefits not specifically related to physical activity, such as helping young people develop socialization, teamwork and body language skills, and fostering healthy habits. Above all, the authors highlight the fact that improving physical fitness among school kids is a fundamental short- and long-term aspect of good health, given the high rates of obesity and physical inactivity among young people, which the authors refer to as “a public health problem that must be addressed by schools.”


 

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De izq. a dcha: Antonio García-Hermoso, Mikel Izquierdo y Robinson Ramírez en una imagen de archivo.
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UPNA, the Education Department and Navarrabiomed participate in physical activity observatory for 3- to 6-year-old children in Navarra

Author
UPNA

Researchers from the Public University of Navarra (UPNA), Navarrabiomed and the Education Department of the Government of Navarra participated in a research project financed by the Navarra Education Department to create the first Physical Education Observatory for 3- to 6-year-old children in Navarra. They were Alicia Alonso, Mikel Izquierdo and Alazne Antón (UPNA), Antonio García-Hermoso and Robinson Ramírez-Vélez (Navarrabiomed), and Berta Villoslada and Berta Echavarri (CIP FP Lumbier-Education Department, Government of Navarra).

The Observatory is meant to promote physical activity in schoolchildren, reducing their screen time and adding relaxation time instead, as it has been shown that developing healthy habits in childhood is crucial to preventing cardiovascular disease in adult life. In order to achieve its goal, the Observatory will conduct a series of assessments in local schools, with children and their families, testing their fitness, measuring their sleep time and analysing all this information with them. The evaluation includes physical tests (jumping with both feet, speed/agility tests, etc.), body composition analysis (waist circumference, percentage of body fat and body mass index) and the use of personal electronic devices to measure the intensity of everyday activity and rest/sleep periods. In addition, the correlation will be established between fitness and school achievements.

The study is set to begin in Colegio Santa María la Real-Maristas Pamplona in October, then moving to Colegio Público San Juan de la Cadena. Finally, there will be a special teacher training module in CIP FP Lumbier, targeted at the students in the higher education training cycles (80), who will become assessors. This will be part of the module titled ‘Fitness testing and response to accidents’.

Throughout the process, school teachers will participate in measurements and evaluations, in an effort to introduce new trends, methods and formulas in children health assessment. According to the authors of the study, ‘the results might help understand why schoolchildren are gaining weight and their performance at school is worsening, with low levels of physical activity.’

Childhood as a critical period to develop healthy habits

‘Early childhood is a critical period for physical, social and cognitive development, to establish healthy behaviour patterns that can be kept into adulthood,’ the researchers say. Studies show that ‘regular participation in physical activities by pre-schoolers is essential for normal development and growth, with immediate and long-term benefits for physical and psychological wellbeing,’ they add. However, they explain, evidence for this age group is still relatively scarce as compared to the data available for children and adolescents aged 6 to 17.

Recently, the World Health Organisation (WHO) published new guidelines on physical activity, sedentary behaviour and sleep for children under 5 years of age. According to these recommendations, children 3-5 years of age should spend at least 180 minutes in a variety of types of physical activities, of which at least 60 minutes is moderate- to vigorous-intensity activity. ‘Despite the benefits for health of regular physical activity, many pre-schoolers fail to meet these standards,’ the authors of the study state. The Observatory is aimed at improving results in this area.

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Antonio García Hermoso, Berta Echávarri Videgain, Berta Villoslada Huarte, Alicia Alonso Martínez, Alazne Antón Olóriz and Mikel Izquierdo Redín.
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SENSORFIT-4HEART para avanzar hacia un tratamiento personalizado de pacientes con ICFEP
SENSORFIT-4HEART para avanzar hacia un tratamiento personalizado de pacientes con ICFEP
Mikel
Izquierdo Redín
Investigador principal
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Functional training space
Installations
Colaboradores/as
Aguado Jiménez, Roberto
Ciencias de la Salud. Navarrabiomed-Universidad Pública de Navarra
Alonso Martínez, Alicia
Ciencias de la Salud. Navarrabiomed-Universidad Pública de Navarra
Unidad de investigación / Grupo Vinculado
Contacto
Physical Activity, Ageing and Fragility (CIBER)

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Translational Cardiology

Translational Cardiology

The Translational Cardiology Unit at Navarrabiomed is formed by a consolidated work team in which professionals with diverse profiles (biologists, nurses, pharmacists, technicians, clinical cardiologists and cardiac surgeons) complement each other to develop research projects whose working hypotheses are based on the clinical needs of patients.

Our priority research lines are as follows:

  • Study of sex-specific mechanisms in the development of valvular diseases: aortic stenosis, aortic insufficiency and mitral valvulopathy.
  • Identification of new therapeutic targets in valvular diseases. Specifically, analysis of the aldosterone/mineralocorticoid receptor pathway and its targets galectin-3 and lipocalin-2 (NGAL).
  • Study of circulating biomarkers of progression and response to treatment in valvular diseases.
  • Analysis of the interactions between valvular diseases and chronic kidney disease and diabetes.
  • New strategies for the treatment of infectious endocarditis.
Investigador principal
Área de investigación
Cardiology
Study of novel therapeutic targets for different types of cardiovascular diseases
Actualidad

Vanessa Arrieta will present her doctoral thesis on Monday, November 28

Vanesa Arrieta
Author
Navarrabiomed
  • Vanessa Arrieta Paniagua, predoctoral researcher at the Translational Cardiology Unit of Navarrabiomed - IdiSNA will present her doctoral thesis by the Public University of Navarra next Monday, November 28, at 12:00, in the Assembly Hall of Navarrabiomed. 

The doctoral work, entitled "Role of sST2 in myocardial fibrosis in severe aortic stenosis”, has been developed at the University Hospital of Navarra and Navarrabiomed under the direction of Natalia López Andrés, Principal investigator of the Translational Cardiology Unit.

Aortic stenosis is the most common valvular heart disease in Europe and North America affecting 2-7%, depending on the region, in population over 65 years of age. To date, there is no medical treatment that can slow down or reverse the evolution of the disease, so aortic valve replacement (surgical or percutaneous) is the only treatment when symptoms or ventricular dysfunction appear.

This disease produces an abnormal progressive narrowing of the aortic valve that, as a result of pressure overload, causes hypertrophy of the left ventricle. In this process, myocardial fibrosis has an important pathophysiological role, as well as a prognostic role. Initially, myocardial fibrosis is part of a compensatory mechanism, but in advanced stages a focal replacement fibrosis appears, leading to ventricular dysfunction and heart failure. The pathophysiological mechanisms underlying these processes are not fully understood. 

Focal replacement fibrosis can be detected and quantified by cardiac magnetic resonance imaging (MRI) with the delayed enhancement (DE) sequences. The presence of DE in patients with severe aortic stenosis has been shown to be an independent predictor of mortality and unfavourable clinical outcome in this group of patients. However, MRI is an expensive technique with limited availability, so it is not used in the follow-up of this group of patients in routine clinical practice.

The hypothesis of this thesis is that as the levels of soluble ST2 (sST2), a biomarker associated with the process of fibrosis and myocardial remodelling, are elevated in case of aortic stenosis, they may have a prognostic value. Specifically, this study addresses the role of sST2 in myocardial fibrosis in severe aortic stenosis. 
 

Research development 

The work is proposed from a translational point of view, and has a dual goal. First of all, to delve into the pathophysiological role of tSS2 in severe aortic stenosis. To this end, a proteomic study has been carried out to assess the proteins modulated by sST2 in human cardiac fibroblasts and the in vitro effects of sST2 on human cardiac fibroblasts have been investigated. The results have been validated in vitro in a rat model with pressure overload and in myocardial biopsies of patients with aortic stenosis that underwent surgery. 

Likewise, it has been demonstrated that sST2 exerts a deleterious role in human cardiac fibroblasts, on the one hand, affecting the mitochondrial function of the cell and thus increasing oxidative stress and the synthesis of proinflammatory molecules and on the other hand, promoting differentiation to myofibroblasts and increasing the synthesis of profibrotic molecules. These findings were validated in the animal model and in myocardial biopsies of patients with aortic stenosis.

Secondly, from the clinical point of view, a cohort of patients with severe aortic stenosis with surgical indication was analysed to check if the blood levels of sST2 are associated with the DE evaluated by MRI in patients with severe aortic stenosis. Thus, it is observed that patients with severe aortic stenosis with cardiac MRI DE have significantly higher blood levels of sST2 than those without RT. Blood sST2 levels are positively correlated with DE mass and with VI mass in patients with severe aortic stenosis. High levels of sST2 make it possible to identify patients with severe aortic stenosis with DE, without having to perform cardiac MRI, in a simple way that can be applied in routine clinical practice.
 

Dissemination of results 

The work carried out has led to several scientific publications: in 2019, in the journal Clinical Science, “Soluble ST2 promotes oxidative stress and inflammation in cardiac fibroblasts: an in vitro and in vivo study in aortic stenosis”, and in 2020 in the journal Cells, “Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1”.   

In addition, the results have been disclosed at several national and international congresses such as the SEC Congress in Bilbao (in 2015 and in 2017), at the 29th EACTS Annual Meeting in Amsterdam, in 2015 or at the Heart Failure Congress in Paris, in 2017.

 

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Vanessa Arrieta Paniagua, investigadora predoctoral de la Unidad de Cardiología Traslacional de Navarrabiomed y Médica Adjunta en el servicio de Cardiología del Hospital Universitario de Navarra
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In doctoral thesis at UPNA, Jaime Ibarrola identifies roles played by hormone in heart valve disease

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UPNA

Biochemist Jaime Ibarrola Ulzurrun (Pamplona, 1991) has shown for the first time that a hormone is involved in mitral valve prolapse, a heart valve disease that leads to heart failure, and that a series of drugs can have positive effects on this condition. ‘The drugs known as antimineralocorticoids or mineralocorticoid receptor antagonists (MCRAs) are a promising option to reduce mitral valve remodelling. The only existing solution to date was surgery,’ Ibarrola explains. This was the subject of his doctoral thesis at the Public University of Navarra (UPNA).

The mitral valve is the valve between the left atrium and the left ventricle of the heart. Mitral valve prolapse is a condition in which the two valve flaps of the mitral valve do not close smoothly or evenly, but instead bulge (prolapse) upward into the left atrium. Sometimes, the mitral valve does not close tightly, allowing blood to flow backward in the heart. This condition is known as mitral valve regurgitation or mitral insufficiency. Most people with mitral valve prolapse – one of the most common heart conditions, affecting 176 million people around the world – never have problems. They do not need treatment or lifestyle changes. Some, however, do need to be treated. ‘To date, no drugs have been developed for this condition, so the only viable solution is surgery,’ Ibarrola explains. His doctoral advisor was Natalia López Andrés, senior researcher at the Cardiovascular Translational Research Unit of Navarrabiomed, a joint centre of the Government of Navarra and the Public University of Navarra (UPNA).

New therapeutic targets

Ibarrola’s research responds to the need to study ‘new mechanisms and new therapeutic targets in order to find drug treatments for mitral valve prolapse.’ ‘Mineralocorticoids are a class of hormones produced by the human body. The primary mineralocorticoid is aldosterone. The aldosterone/mineralocorticoid receptor (Aldo/MR) pathway can cause cardiac fibrosis. In addition, a large number of studies have shown that the Aldo/MR pathway is involved in a number of heart conditions. MCRA drugs can block the effects of the Aldo/MR pathway. Moreover, significant clinical studies show that they can also improve cardiac function by reducing cardiac fibrosis,’ Ibarrola explains. He conducted his doctoral research project with financial aid from UPNA and a European programme.

Ibarrola worked on the hypothesis that the Aldo/MR pathway could play a role ‘in the development of mitral valve prolapse, modulating cell activation and cellular differentiation.’ ‘Furthermore, the Aldo/MR pathway could become a new therapeutic target in this disease, and blocking this pathway with MCRA drugs could prevent the alterations associated with mitral valve prolapse. For the first time, we were able to show that the Aldo/MR pathway is involved in the development of mitral valve prolapse and that the drugs could have a positive effect on this condition,’ Ibarrola concludes. His doctoral thesis got an A-grade cum laude.

Ibarrola’s résumé

Jaime Ibarrola holds a degree in Biochemistry and a master’s degree in Biomedical Research from the University of Navarra. At present, he is a postdoctoral researcher at the Molecular Cardiology Research Institute (MCRI) at Tufts University (Massachusetts, USA).

As a doctoral student, Ibarrola was twice a visiting scholar at the Cordeliers Research Centre, Sorbonne University, in Paris. He shared his results in eight international conferences in Germany, Spain, France and Ireland. Ibarrola is the author of about a dozen papers published in international scientific journals.

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Infective endocarditis
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López Andrés
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Álvarez Asiain, Virginia
Hospital Universitario de Navarra
Arrieta Paniagua, Vanessa
Hospital Universitario de Navarra
Beunza Puyol, Mª Teresa
Hospital Universitario de Navarra
Ciriza Esandi, Mercedes
Hospital Universitario de Navarra
Conty Cardona, Aritza
Hospital Universitario de Navarra
Escribano Arellano, Elena
Hospital Universitario de Navarra
García de la peña Urtasun, Amaia
Área de salud de Estella
Navarro Echeverría, Adela
Hospital Universitario de Navarra
Roy Añón, ignacio
Hospital Universitario de Navarra
Sádaba Cipriain, Alba
Hospital Universitario de Navarra
Sádaba Sagredo, Rafael
Hospital Universitario de Navarra
Tiraplegui Garjon, Carolina Rosa
Hospital Universitario de Navarra
Vera Sainz, Alberto
Hospital Universitario de Navarra
Unidad de investigación / Grupo Vinculado
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Translational Cardiology

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Neuroepigenetics

Neuroepigenetics

Our aim is to describe the DNA methylation pattern and its influence on the development of neurological diseases, as well as identify epigenetic biomarkers for diagnosis, prognosis and therapeutic monitoring. To this end, we use advanced techniques and procedures of Personalized and Precision Medicine, such as liquid biopsy, ELISA and digital PCR. Our main area of interest is neurodegenerative diseases and post-stroke cognitive decline. In addition, we work to define the epigenetic bases involved in adult neurogenesis and that influence both neurodegeneration and resilience to these processes, in order to find therapeutic targets. Our research incorporates the analysis of sex- and gender- related differences across the different pathologies.

Research lines:
•    Identification of Epigenetic Biomarkers in Alzheimer's disease and other Neurodegenerative Diseases.
•    Precision and Personalized Medicine in the diagnosis of dementias.
•    Mechanisms of neurogenesis and resilience in Alzheimer's disease: new therapeutic targets.
•    Identification of Epigenetic Biomarkers of post-stroke cognitive impairment (PSCI).

The group belongs to the ISCIII RICORS network for cerebrovascular diseases, to the national DEGESCO consortium (Dementia Genetics Spanish Consortium) and participates in the SCAP-AD (IMPACT 2022, ISCIII) Personalized and Precision Medicine project.
 

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Neuroscience
DNA methylation in neurodegenerative diseases such as Alzheimer’s. #NeuroEpigenTransforms
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Iván Méndez-López will present his doctoral thesis on Monday, December 19

Author
Navarrabiomed

Iván Méndez-López, clinician and predoctoral researcher at the Neuroepigenetics Unit from Navarrabiomed - IdiSNA will present his doctoral thesis by the Public University of Navarra next Monday, December 19, at 12:00 in the assembly hall of Navarrabiomed.

The doctoral work, which is entitled "Blood pressure targets for hypertension in people with chronic renal disease", has been developed in the Internal Medicine Service of the University Hospital of Navarra and Navarrabiomed, under the direction of Doctors Juan Erviti López and Luis Carlos Saiz Fernández, researchers of the Innovation and Organization Unit of the Navarra Health Service-Osasunbidea. 


Research development

So far there is no established evidence about the optimal blood pressure figures in people with arterial hypertension (AHT) and chronic kidney disease. Using the proven methodology of the Cochrane organization, Méndez-López's work has carried out the first systematic review that addresses this issue with individualized patient data. After the inclusion of 7,348 patients from six clinical trials, it is concluded that an intensive reduction in blood pressure does not provide greater health benefits than those obtained with a standard reduction in blood pressure (BP) in patients with AHT and chronic kidney disease. The relevance of these conclusions suggests that the current recommendations of BP targets for this population should be amended by the international clinical practice guidelines. 


Dissemination of results

The work carried out has led to a scientific publication in 2019, in the Cochrane Database of Systematic Reviews (CDSR), the main journal and database of systematic reviews in health care: “Blood pressure targets for hypertension in people with chronic renal disease”. In addition, partial results of the study have been disseminated at the thirty-first European Meeting on Hypertension and Cardiovascular Protection, held in June 2022 in Athens, Greece. 

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Amaya Urdánoz will present her doctoral thesis on Tuesday, July 5th

Author
Navarrabiomed

The predoctoral researcher of the Neuroepigenetics Unit of Navarrabiomed, Amaya Urdánoz Casado, will be sitting her viva from the Public University of Navarra next Tuesday, July 5th at 11:00 in the Assembly Hall of Navarrabiomed.


The doctoral work, entitled "Identification of circRNAs as candidate epigenetic biomarkers in Alzheimer's disease”, has been developed at Navarrabiomed under the direction of Maite Mendioroz Iriarte and Idoia Blanco Luquin.

This research focuses on Alzheimer's disease (AD), a neurodegenerative, chronic and, at the moment, irreversible disease that represents the first cause of age-related dementia. It is postulated that circular RNAs (circRNAs) play important roles in brain homeostasis, as well as in the development of neurodegenerative diseases. 
The objective of this doctoral thesis is to identify, in patients with AD compared to controls, circRNAs with differential expression in the human entorhinal cortex (CE), a brain region especially vulnerable to AD. To do this, the study of the expression of circRNAs is proposed using a candidate gene and a genome-wide approach.
In the former, candidate gene approach, 10 genes were selected, whose role in AD had already been described in the literature and from which circRNAs originated. 6 circRNAs derived from the APP, ADAM10, CDR1 and HOMER1 genes were identified, of which 4 showed a differential expression in EC between patients with AD and controls. In addition, three potential circRNAs derived from the TREM2 gene were identified for the first time in the EC.

In the second genome-wide approach, new circRNAs differentially expressed in the EC were identified that so far had not been associated with the development of the disease by transcriptome sequencing in patients with AD with respect to controls. In addition, several circRNA-miRNA-mRNA interaction networks (competitive endogenous RNA network, ceRNET) were predicted.
The results obtained show the deregulation of a series of circRNAs in the EC affected by AD with respect to controls, suggesting their potential involvement in the pathogenesis of the disease.


Disclosure of results and financing

The work carried out has resulted in a scientific publication in the International Journal of Molecular Sciences, “Gender-Dependent Deregulation of Linear and Circular RNA Variants of HOMER1 in the Entorhinal Cortex of Alzheimer's Disease”.
In addition, it has been disseminated at several national and international congresses, the Alzheimer's Association International virtual Conference Satellite Symposium, the 15th International virtual Conference on Alzheimer's and Parkinson's Diseases: Mechanisms, Clinical Strategies and promising Treatments of Neurodegenerative Diseases or at the BraYn Conference: Second brainstorming research assembly for young neuroscientists.

For the development of the thesis, Amaya Urdánoz has received several grants for the recruitment of doctoral students by companies and research and knowledge dissemination organizations: industrial doctoral students 2018-2020 and grants for the financing of a predoctoral contract in health sciences and technologies in the period 2019-2022, both funded by the Government of Navarra. She also received an Erasmus scholarship for her stay at Karolinska Intitutet and an aid for the mobility of doctoral students - UPNA Congresses (2021) to attend, with a communication of her research, the 15th International virtual Conference on Alzheimer's and Parkinson's Diseases: Mechanisms, Clinical Strategies and promising Treatments of Neurodegenerative Disease.

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‘la Caixa’ Foundation, Caja Navarra Foundation and Navarrabiomed launch programme to foster public biomedical research in Navarra

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Navarrabiomed
  • The programme will offer support to the development of studies in digestive medicine, geriatrics, neuroscience and oncology that will bring advancement and excellence in these fields of research.
  • ‘la Caixa’ Foundation and Caja Navarra Foundation are channelling 1.2 million Euro into this programme, to be run by the biomedical research centre Navarrabiomed, where four doctors from the Navarra Health System-Osasunbidea (SNS-O) will carry out quality biomedical research studies.
  • Through this programme, ‘la Caixa’ Foundation and Caja Navarra Foundation will give support to the leading research centres in Navarra during the 2017-2021 period. Universities and research centres will thus get a total 6.4 million Euro.

Ana Díez Fontana, Regional Director of CaixaBank in Navarra; Javier Miranda, Chairman of Caja Navarra Foundation; and Iñigo Lasa, Director of Navarrabiomed, announced the research lines to be developed by doctors Eduardo Albéniz Arbizu, Nicolás Martínez Velilla, Maite Mendióroz Iriarte and Antonio Viudez Berral, who were selected by an external evaluation committee from 12 candidates.

The specialists in the programme will be relieved from part of their medical activity so that they can do research. They need time to develop their scientific projects and produce new knowledge in their medical specialties. The initiative enables the establishment of a critical mass of professionals that combine medical activity with research jobs, thus promoting translational medicine to the benefit of patients and society as a whole.

The four doctors selected to join the programme will soon start working at the labs of Navarrabiomed – the joint biomedical research centre of the Government of Navarra and the Public University of Navarra (UPNA). They will establish separate research units for the development of their projects, based on clinical practice at the Navarra Hospital Complex (CHN), with support from other Navarrabiomed units and platforms.

In addition to streamlining research activities in the respective units, they will encourage the participation of resident medical interns (MIRs) by getting them involved in biomedical research projects, trials and programmes.

Four excellent research projects in digestive medicine, geriatrics, neuroscience and oncology

Eduardo Albéniz Arbizu has worked in a number of hospitals across Spain. He received training in advanced endoscopy in France, Japan and China. Currently, he is working at the Gastrointestinal Endoscopy Unit of the CHN Digestive Medicine Service.

Dr Albéniz specialises in endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for the removal of early-stage gastrointestinal tumours. These advanced procedures reduce the number of surgical and other more invasive interventions in the treatment of superficial neoplastic lesions. Resection of colorectal polyps, for example, is the procedure with the highest survival rates observed in screening studies for colorectal cancer carried out in Navarra.
The goal of the project led by Dr Albéniz is to provide evidence for the identification of predicting factors for the effectiveness of resection procedures and other factors associated with potential complications that might be minimised.

Nicolás Martínez Velilla has been the Head of the Geriatrics Unit at CHN since 2015. In 2013, he was appointed head of a team partnered with Navarrabiomed for the promotion of research into different aspects of geriatric medicine.

Dr Martínez Velilla’s proposal includes a thorough study for the prevention of old-age frailty and disability or dependency in hospitals and in the community at large. Furthermore, it includes the creation of a European cross-border network to deal with various aspects of ageing. The project is aimed at rethinking hospitalisation of older adults, prescribing exercise to older patients in hospitals so as to improve their quality of life and increasing the sustainability of the health system.

Maite Mendióroz Iriarte has built her professional career as a doctor and researcher in Pamplona, Barcelona, San Sebastián and New York. Since 2010, she has been a member of the Neurology Department at CHN. Over the past few years, she has received grants from ‘la Caixa’ Foundation, Caja Navarra Foundation and the Government of Navarra to boost activity in the Neuroepigenetics Unit at Navarrabiomed.

Between 2018 and 2021, Mendióroz Iriarte will develop a project whose goal is to identify a potential blood-based epigenetic biomarker for early detection and treatment of Alzheimer’s disease. Her study might become the first step towards the implementation of precision medicine in neurodegenerative diseases.

Antonio Viudez Berral has developed his professional career in Navarra, Catalonia and Baltimore, USA. In 2010, he joined the Medical Oncology Service at CHN. Since then, he has been a researcher at Navarrabiomed as well.

Dr Viudez’s project will study pancreatic neuroendocrine tumours to find accurate markers that predict the effectiveness of certain therapies.

In addition, the Medical Oncology Service will be able to strengthen its scientific activity, establishing new lines of research for the improvement of diagnosis, prognosis and prediction of treatment response and toxicity.

From left to right: Luis Gabilondo, Ana Díez, Maite Mendióroz, Eduardo Albéniz, Antonio Viudez, Nicolás Martínez, Javier Miranda and Iñigo Lasa.

 

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Luis Gabilondo, Ana Díez, Maite Mendióroz, Eduardo Albéniz, Antonio Viudez, Nicolás Martínez, Javier Miranda and Iñigo Lasa.
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CHN and Navarrabiomed publish innovative study on liquid biopsy for amyotrophic lateral sclerosis diagnosis and follow-up

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Navarrabiomed

The Navarra Hospital Complex (CHN) and the biomedical research centre Navarrabiomed have carried out an innovative study of the so-called ‘liquid biopsy’ in amyotrophic lateral sclerosis (ALS) diagnosis and follow-up. The results of this study were published in the international peer-reviewed journal Annals of Translational Medicine.

On the occasion of the Global ALS Awareness Day, members of the multidisciplinary team treating patients with ALS in Navarra shared the latest research and care developments in connection with this disease, including this innovative study of the use of liquid biopsy testing in ALS diagnosis and follow-up.

The leaders of the study were Maite Mendióroz and Ivonne Jericó, doctors from the CHN Neurology Department and researchers at Navarrabiomed. The project was part of the scientific activity done at the Navarra Medical Research Institute (IdiSNA), a public-private agency for the promotion of biomedical research in Navarra. The survey involved ALS patients and a control group (individuals without ALS), and professionals from the departments of Neurology and Anaesthesiology and the Nursing Team at CHN, and the Neuroepigenetics Unit at Navarrabiomed.

According to the study coordinators, one of the biggest weaknesses in research into neurodegenerative disease is the difficulty to access and study the nervous tissue of living patients. In order to address this difficulty, the study analyses the application of liquid biopsy testing, a technique recently developed in the field of cancer research, to ALS diagnosis.

Liquid biopsy is based on the fact that, when cells degenerate and die, their contents – including DNA – flow into the bloodstream. The released DNA molecules contain biochemical information about the original cells (hence the name ‘biopsy’) – in this case, diseased neurons. The original cell contents can be isolated and analysed in blood samples (hence the name ‘liquid’). The researchers have successfully used this technique with ALS patients to identify a new gene, RHBDF2, as a biomarker for ALS diagnosis in the future.

‘To the best of our knowledge, this is the first time ever liquid biopsy has been used to diagnose neurodegenerative diseases. The results have been encouraging so far. Now we are planning to extend the technique to other neurodegenerative diseases, such as Alzheimer’s disease,’ the doctors said, adding that the survey was made possible by the generous participation of patients and their families, and the volunteers in the control group.

A multidisciplinary team, 11 years and more than 200 patients

The team treating ALS patients in Navarra have striven to promote ALS research right from the start. Currently, two researchers at the Navarrabiomed Neuromuscular Disease and Motor Neuron Disease Group (headed by Dr Jericó) are working on ALS for their PhD projects, and other four projects address this neurodegenerative disease – specifically, the identification of biomarkers for diagnosis and follow-up, the role of neuroinflammation, the underlying mechanisms, the analysis of genetic factors, and the study of epidemiological aspects and disability.
The Group coordinates both research and care activities, and collaborates with the Navarrabiomed Proteomics and Biobank platforms, the Neuroepigenetics Research Unit (headed by Dr Mendióroz) and the Navarra Public and Occupational Health Service (Rare Disease Registry).

Amyotrophic lateral sclerosis is a progressive nervous system disease with a heterogeneous clinical presentation but common symptoms like muscle weakness and progressive muscular atrophy. Prognosis is variable among patients. About 5 to 10 per cent of ALS is familial, which means it arises in families in which there is a history of ALS. The other 90 to 95 per cent of ALS is sporadic, meaning it occurs without a family history, its causes still being unknown. Every year, 1 to 2 people every 100,000 are diagnosed with ALS. Despite being a rare disease, it has a deep social and family impact. Currently, there is no cure for ALS, but this does not mean there is no treatment.

ALS care involves multiple disciplines. On the occasion of the Global ALS Awareness Day the multidisciplinary team at CHN shared an informative brochure with patients and their families, highlighting the importance of coordinated social and health care through multidisciplinary units or teams. Active for 11 years now, the CHN team have treated over 200 patients to date.

Navarra has been one of the first Spanish regions to implement a multidisciplinary care model for ALS patients. Since 2007, the region has been offering comprehensive, coordinated care to them and their families, through a multi- and interdisciplinary team whose members include a neurologist, (Dr Ivonne Jericó), a nutritionist (Dr Ana Zugasti), two pulmonologists (Dr Joan Boldú and Dr Begoña Fernandez), a neurophysiologist (Dr Asun Ibiricu), an intensive care physician (Dr Juan Pedro Tirapu), a social worker (Rakel Suescun), neurology nurses, dieticians, a palliative care service and members of the Psychological and Social Support Service at San Juan de Dios Hospital (Yolanda Santesteban and Ana Baños).

From the beginning, the team set out to offer adequate, tailored, patient-centred social and health care, while promoting research as the key to finding an effective treatment for ALS.
 

Image: Members of the multidisciplinary team treating patients with ALS in Navarra.

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IBEAS - PLUS
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Maite
Mendioroz Iriarte
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Jericó Pascual, Ivonne
Hospital Universitario de Navarra
Herrera Isasi, María
Hospital Universitario de Navarra
Altuna Azkargorta, Miren
Universidad del País Vasco
Martínez-Lage, Pablo
Fundación CITA-alzhéimer Fundazioa
García-Campayo, Javier
Hospital Universitario Miguel Servet
Unidad de investigación / Grupo Vinculado
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Neuroepigenetics

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Clinical Neuroproteomics

Clinical Neuroproteomics

The unit focuses on characterizing the molecular mechanisms involved in the development of neurodegenerative diseases. With this objective, the group investigates proteins and peptides involved in neuropathogenic processes in diseases such as Alzheimer's and Parkinson's. To this end, the team uses multi-omics approaches that allow them to identify and quantify hundreds of genes/proteins in brain samples, both human and from disease models. Through bioinformatic analyses and Systems Biology, they identify disease-specific molecular pathways and mechanisms, characterizing proteins with potential prognostic and/or diagnostic value. Given the early olfactory dysfunction present in multiple neurological syndromes, the group has recently focused its efforts on characterizing olfactory structures, with the aim of developing future intranasal treatments with the potential to improve cognitive function.


The unit is part of the Spanish Olfactory Network (ROE), the Global GCCR International Consortium (Global Consortium for Chemosensory Research) as well as the Human Brain Proteome Project (HBPP).
 

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Neuroscience
Identification of proteins and peptides in neuropathogenic processes
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Navarrabiomed participates in international research project demonstrating loss of smell and taste in COVID-19 patients

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Navarrabiomed

•    A consortium made of more than 600 professionals from 50 countries highlights the importance of confirming the diagnosis of people presenting with alterations in their capacity to smell and taste
 

Navarrabiomed is participating in an international research project that has confirmed that most people suffering from COVID-19 experience a loss of their sense of smell and/or taste. This initiative is part of an international consortium made up of more than 600 professionals from 50 countries.

Enrique Santamaría Martínez PhD, Head of the Navarrabiomed Clinical Neuroproteomics Unit, is responsible for leading the center’s participation in an international consortium that has confirmed the direct relationship between COVID-19 and anosmia (loss of the sense of smell) and the reduction in taste capacity in early stages of the disease. More than 600 professionals from 50 countries are collaborating on this study, whose findings may determine who is given diagnostic tests in new outbreaks.

On 7 April 2020, the Global Consortium for Chemosensory Research (GCCR) launched a massive survey with the aim of gathering sensory information on the ability to smell and taste of participants, people diagnosed with an objective test such as PCR or after clinical assessment no more than 15 days prior to responding to the survey. Among other variables, participants were asked to quantify their smell, taste and chemesthesis function (their capacity to smell, taste and perceive cooling, tingling and burning sensations in the mouth) before and while suffering from COVID-19 disease. They were also asked to mention any kind of nasal obstruction that had occurred.

The consortium obtained preliminary results 11 days later, on 18 April, and published the findings on 8 May in the free-access repository medrxiv.org. A total of 4,039 people from more than 40 countries filled out the survey and an analysis of the results indicates that smell, taste and chemesthesis were significantly reduced in patients diagnosed with COVID-19 disease. It is important to point out that nasal obstruction does not seem to be associated with these losses, which suggests that it may be an indicator for differentiating infection from SARS-CoV-2 from other viral infections such as cold and flu (which do produce nasal obstruction).

The reduction in the capacity to smell and taste may be taken as a distinctive characteristic of possible cases of COVID-19 arriving at hospitals and health centers and that require confirmation by means of a diagnostic test.

The project is different from previous studies on chemosensory abilities and COVID-19 because it proposes a massive international approach within a collaborative open-science framework. The study is led by Valentina Parma (Temple University, Philadephia, USA), John Hayes (Penn State, USA), Thomas Hummel (Technische Universität Dresden, Alemania), Steve Munger (Universidad de Florida, USA) and Danielle Reed (Monell Chemical Senses Center, USA). 

Research in progress

The consortium has now received more than 37,000 responses and the survey is still active. Navarrabiomed encourages anyone who has recently suffered from a respiratory disease, including COVID-19, to go online to https://gcchemosensr.org/ and fill out the survey in one of the 29 languages available. “Patient participation is key for determining the symptomatology of SARS-CoV-2. Consortium committees are currently organizing specific research projects that will make use of all the information compiled in the GCCR initiative,” said Dr. Santamaría.

The Navarrabiomed Clinical Neuroproteomics Unit is interested in determining why COVID-19 patients lose their sense of smell. To answer this question, the Unit is collaborating with the group of Dr. David Escors (Head of the Oncoimmunology Unit, Navarrabiomed) in order to untangle the molecular mechanisms that are altered at the olfactory level by the SARS-CoV-2 virus.

“One of the coronavirus’s access routes is through the nasal cavity, which is why analysis of the “nose-brain” route could provide information on why strokes, seizures and encephalitis have been observed in some COVID-19 patients”.

Furthermore, according to preliminary results from the seroprevalence study carried out by the Spanish Ministry of Health and the Carlos III Health Institute, the loss of smell should not merely be considered an early symptom of COVID-19 disease, but also a predictor of immune response,” Dr. Santamaría said.

The Navarrabiomed Neuroproteomics Unit, in collaboration with public and private health institutions in Navarre, is currently working on the development and deployment of precision olfactory medicine, which, together with immunological analysis, will lead to more effective diagnosing and monitoring of the many diseases involving loss of smell, one of which is COVID-19.
 

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Navarrabiomed researchers coordinate the publication of a book on brain protein analysis

Author
Navarrabiomed

LEnrique Santamaría and Joaquín Fernández-Irigoyen, researchers at the Proteomics Unit of the biomedical research centre Navarrabiomed, were the coordinators of Current Proteomic Approaches Applied to Brain Function, released by the academic publishing company Springer Nature as part of its Neuromethods collection.

The book introduces 20 standard protocols to deepen the knowledge of proteins and their role in neurodegenerative and psychiatric disorders.

In this book, Santamaría and Fernández-Irigoyen, who are also professionally related to the Navarra Medical Research Institute (IdiSNA) and the ProteoRed-ISCIII national platform, offer a compendium of methods for brain proteome quantification, post-translational modification monitoring, neuronal organelle identification and characterisation, and bioinformatics tool implementation for omics data integration. It is meant to be an essential guidebook for students a valuable resource for graduate students and postdoctoral fellows interested in neuroproteomics, as well as for researchers looking for further insight into the growing field of mass spectrometry in neuroscience.

Book contributors included as many as 75 researchers from labs in Spain, Switzerland, France, Denmark, Portugal, Germany, India, the USA and Brazil. Many of them are regular participants in The Human Brain Proteome Project (HBPP).

HBPP is an international initiative sponsored by the Human Proteome Organisation (HUPO) promoting proteomic studies on the human brain and follow-up projects to decipher the role of proteins in brain development, health and disease.

 

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Navarrabiomed researchers Joaquín Fernández-Irigoyen and Enrique Santamaría.
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INNOLFACT  Implementing Olfactory Precision Medicine
INNOLFACT Implementing Olfactory Precision Medicine
Enrique
Santamaría Martínez
Head of the Unit
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Clinical Neuroproteomics
Lab
Unidad de investigación / Grupo Vinculado
Contacto
Clinical Neuroproteomics

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Molecular Pathology of Cancer

Molecular Pathology of Cancer

The Cancer Molecular Pathology Research Unit is composed of researchers from Navarrabiomed and clinical researchers from the Pathology Department, Surgery and other services at the University Hospital of Navarra. Its fundamental objective is the detection of new genetic and epigenetic biomarkers related to prognosis and response to oncological treatment in patients with different types of cancer, mainly breast cancer, colorectal cancer, gynecological cancers, and brain tumors among others. For this, we use massively parallel sequencing (NGS) on tissue and liquid biopsy, as well as single-gene molecular techniques such as pyrosequencing, real-time PCR, etc.

The unit collaborates with other research groups at Navarrabiomed and at other institutions (IUOPA, Oviedo; PEBC-IDIBELL, Barcelona).


Research lines:

  1. Analysis of aberrant methylation (hypo- and hypermethylation) and presence of alterations (mutations, indels, copy number variations, fusions) in genes involved in the progression of solid tumors.
  2. Analysis of the prognostic and predictive value of these biomarkers for response to oncological treatment.
  3. Analysis of protein expression profiles in relation to tumor characteristics.
  4. In vitro functional assays.
     

 

Investigador principal
Equipo de investigadores
Área de investigación
Oncology
Molecular Pathology of Cancer
Actualidad

Saioa Mendaza Lainez defenderá su tesis doctoral el martes, 30 de junio

Author
Navarrabiomed

Saioa Mendaza Lainez, investigadora predoctoral en la Unidad de Patología Molecular del Cáncer de Navarrabiomed, realizará la lectura de su tesis doctoral por la Universidad Pública de Navarra el martes 30 de junio, a las 11:30, a través de videoconferencia en Navarrabiomed (solamente podrán acudir aquellas personas autorizadas previamente). 

La tesis, titulada Approaching the epigenome of triple-negative breast cancer to identify new biomarkers, ha sido desarrollada en Navarrabiomed bajo la dirección del Dr. David Guerrero Setas y la Dra. Esperanza Martín Sánchez.


El cáncer de mama es la neoplasia más frecuente en mujeres a nivel mundial y la primera causa de muerte por cáncer en este mismo sexo. La investigación aborda el cáncer de mama triple negativo (CMTN), un subtipo que a diferencia del resto carece de tratamiento dirigido, lo que conlleva consecuencias más agresivas en las personas que lo padecen. Esto hace que a día de hoy, la búsqueda de nuevos biomarcadores y dianas terapéuticas para esta enfermedad sea imprescindible.

Dado que las alteraciones epigenéticas están involucradas en la tumorigénesis, el objetivo de esta tesis ha sido caracterizar la metilación del DNA y la acetilación de histonas de este tipo de cáncer. Con ello se ha buscado identificar nuevas firmas potencialmente diagnósticas y pronósticas, así como alteraciones destinatarias de fármacos dirigidos.

Los resultados de esta caracterización han permitido concluir que el patrón epigenético está alterado en CMTN respecto a tejido mamario no neoplásico. Más importante aún, la investigación ha desvelado dos alteraciones epigenéticas específicas como potenciales biomarcadores de peor pronóstico: la acetilación de la histona H4K5 y la hipometilación del gen ADAM12, el cual se presenta también como posible diana terapéutica frente a este cáncer.

Asimismo, se ha identificado una nueva firma basada en metilación de DNA con utilidad diagnóstica. Por último, se han descrito los procesos biológicos de los distintos genes regulados por la acetilación de H4K6 en líneas celulares no neoplásicas y CMTN.

El trabajo realizado ha dado lugar a tres publicaciones científicas y ha sido difundido en dos congresos consecutivos de European Association for Cancer Research; uno celebrado en Manchester en el año 2017 y en Amsterdam en el 2018.

Para el desarrollo de la tesis Saioa Mendaza ha sido beneficiaria de dos becas: Ayudas para la formación de Personal Investigador de la Univesidad Pública de Navarra  para la realización de tesis doctorales y Beca a la excelencia de la Funcación Caja Navarra para la realización de una estancia en University of Massachussets Medical School (EEUU).

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Vídeo
Colaboradores/as
Amat Villegas, Irene
Hospital Universitario de Navarra
Armendáriz Rubio, Pedro
Hospital Universitario de Navarra
Arriola Osés, Marta
Hospital Universitario de Navarra
Córdoba Iturriagagoitia, Alicia
Hospital Universitario de Navarra
Guarch Troyas, Rosa
Hospital Universitario de Navarra
Ruiz de Azua Ciria, Ana Yerani
Hospital Universitario de Navarra
Zazpe Cenoz, Idoya
Hospital Universitario de Navarra
Unidad de investigación / Grupo Vinculado
Contacto
Molecular Pathology of Cancer

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Cancer Signalling

Cancer Signalling

The Cancer Signaling Unit is interested in understanding the molecular mechanisms by which cancer cells develop resistance to targeted therapies currently used to treat oncology patients. To that end we have developed three research lines focused on melanoma, glioblastoma, and triple-negative breast cancer. By blocking these adaptive resistance mechanisms, we aim to improve the therapeutic efficacy of treatments such as radiotherapy, targeted therapies, and immunotherapies. The unit's ultimate goal is to translate its results into clinical practice.

Investigador principal
Área de investigación
Oncology
Drug resistance and metastasis
Actualidad

Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy

En verde la tinción de los linfocitos antitumorales tipo NK y en azul, las células tumorales.  ➡️ El tratamiento con #ranolazina aumenta la cantidad de linfocitos antitumorales que infiltran el tumor y favorecen la acción de la inmunoterapia.
Author
Navarrabiomed

A study led by Navarrabiomed proposes a therapeutic alternative to treat melanoma.

  • The drug ranolazine, used to treat chronic angina pectoris, could improve response to anti-melanoma therapies.
  • This is a multicenter investigation carried out by Navarrabiomed biomedical research center, the Institute for Neurosciences CSIC-UMH, and IRB Barcelona.

The prestigious journal Nature Metabolism has published the results of a study in mice that determined that ranolazine, a drug that is currently administered to patients to treat heart conditions, delays the appearance of resistance to melanoma treatments, by blocking fatty acids metabolism. This research has been led by Navarrabiomed, together with the Institute for Neurosciences (CSIC-UMH) and IRB Barcelona. Melanoma is the most aggressive type of skin cancer and, although it only accounts for 10% of skin cancer cases, it is responsible for 90% of deaths associated with skin tumours. Thanks to the development of targeted therapies and immunotherapies, the clinical management of patients affected with this type of cancer has improved, however, these therapies still have limitations because 50% of patients do not respond adequately and even develop resistance.

The evidence suggests that this resistance could be linked to metabolic reprogramming in cancer cells that is associated to changes in the way in which cells process and use nutrients. This research demonstrates that fatty acid metabolism plays an important role in the development of resistance to melanoma treatments.

Researchers have confirmed that increased fatty acid oxidation occurs during long-term treatment with BRAF inhibitors, one of the key genes in tumour progression, contributing to therapy resistance.

Ranolazine increases the efficacy of targeted therapy against melanoma because it can target fatty acid oxidation. In addition, the application of this drug promotes that melanoma cells become more visible to the immune system,improving the response to immunotherapies and increasing the ability of lymphocytes to control tumour growth.

A multicenter investigation

The Navarrabiomed Cancer Signaling Unit, directed by Imanol Arozarena Martinicorena, has coordinated the course of the research and has been in charge of carrying out the experiments related to resistance to targeted therapies and the study of how ranolazine affects the immunogenicity of melanoma cells.

Researchers at the laboratory led by Berta Sánchez-Laorden, belonging to the Cell Plasticity in Development and Disease group at the Institute for Neurosciences, have developed immunotherapy experiments in mice and have carried out the study of immune cells in the tumour microenvironment.

In addition, the IRB Barcelona Stem Cells and Cancer research group, led by Salvador Aznar-Benitah, has carried out individual cell RNA sequencing analyses, which have made it possible to find out in detail the effect of the drug on the state metabolism of tumour cells.

Funding

This study, which has been made possible thanks to funding granted by the Ministry of Science and Innovation, the Carlos III Health Institute, the Government of Navarra, the Spanish Multidisciplinary Melanoma Group (GEM), and the Melanoma Research Alliance, is a clear example of how basic research can contribute a lot to the repositioning of drugs, which makes it possible to significantly shorten the deadlines for providing answers to patients suffering from diseases as prevalent as cancer.

Categoría
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Marta Redondo and Imanol Arozarena, responsible for this research in Navarrabiomed
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Single cell sequencing analysis of different immune populations infiltrating untreated melanoma tumors or treated with ranolazine (Rano), immunotherapy (PDL1) or the combination of both (PDL1+Rano).
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Treatment with ranolazine increases the number of antitumour lymphocytes (green) that infiltrate the tumour(b lue) and favour the action of immunotherapy
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SARAY funds Navarrabiomed with 46,970 euros for two projects on metastatic breast cancer

Author
Navarrabiomed
  • Since 2015 the associations annual investment in research has been increased by 65%


On October 27th, 2019 Breast Cancer Association of Navarre SARAY collected 75,000 euros in the solidarity race celebrated in Pamplona. 49,970 euros will fund two studies developed by Navarrabiomed on metastatic breast cancer.

One of the projects is focused on liquid biopsy in this type of cancer, and it is led by Natalia Ramírez Huerto, the head of the Hematological Oncology Unit of Navarrabiomed. SARAY´s contribution for the second year of the project development raises to 24,970 euros. Other study lead by Cancer Signaling Unit head Imanol Arozarena Martinicorena will receive 22,000 euros. His project aims to develop new adjuvant therapies to treat brain and bone metastases from these tumors. The additional funds will be donated to the Chronos Hope Project from Solti Foundation.

On the 25th of June SARAY decided to allocate the incomes in a face-to-face and online assembly among 725 associates (event delayed three months later due to the COVID-19 crisis). During the last years, the organization shows a strong commitment with biomedical research performed in Navarre. Therefore, it is relevant to highlight that since 2015 SARAY has increased by 65% its annual investment in oncology research.

 

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Natalia Ramírez Huerto, investigadora principal de la Unidad de Oncohematología
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Imanol Arozarena Martinicorena, investigador principal de la Unidad de Señalización en Cáncer
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Navarrabiomed and University of Manchester researchers publish melanoma review in Nature

Author
Navarrabiomed

Imanol Arozarena, senior researcher from the Cancer Signalling Unit at the Navarrabiomed biomedical research centre and a member of Instituto de Investigación Sanitaria de Navarra (IdiSNA), has recently published a melanoma review with University of Manchester Professor Claudia Wellbrock.

The two scientists were asked by the renowned scientific journal Nature Reviews: Cancer to write an article on the latest findings in melanoma cell distinct phenotypes and their relevance for melanoma development and response to therapy.

As many as 4000 new melanoma cases are diagnosed in Spain every year. Malignant melanoma is a serious type of skin cancer that is usually metastatic. It is notorious for its intra- and inter-tumour heterogeneity.

Such variability results from the ability of melanoma cells (melanocytes) to adjust to changing environmental conditions by reprogramming their genetic expression. Thus, melanocytes develop resistance to both targeted therapy and immunotherapy, and their plasticity plays a role in metastasis development.

In their article, the authors reveal the importance of combining recent developments in genomic technologies and the availability of large gene expression datasets for a precise definition of the gene signatures that characterise changes in each patient’s tumours and the prognostic relevance for tumour development and response to therapy.

According to Arozarena, ‘By understanding the molecular mechanisms that adapt melanoma cells to anti-tumour drugs, we will be able to prevent both therapy resistance and the progression of metastatic melanoma.

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Los autores, Arozarena y Wellbrock
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I-Gliome
I-Gliome
Imanol
Arozarena Martinicorena
Head of the Unit
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360º Virtual Tour
Cancer Signalling
Lab
Colaboradores/as
Wellbrock, Claudia
Universidad Pública de Navarra
Rico Oses, Mikel
Hospital Universitario de Navarra
Zazpe Cenoz, Idoya
Hospital Universitario de Navarra
Larrayoz, Iñaki
Universidad de la Rioja
Labiano, Sara
CIMA
Lecanda, Fernando
CIMA
Aznar Benitah, Salvador
IRB-Barcelona
Unidad de investigación / Grupo Vinculado
Contacto
Cancer Signalling

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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