Noticias

• A researcher from La Rioja has obtained a scholarship to study her postdoc in Navarrabiomed-IdiSNA.
• This young talent receives support within the framework of the Junior Leader postdoctoral scholarship program, which has awarded a total of 45 scholarships in 2021 to excellent researchers.
• The call pursues a dual goal: to support the best Spanish and Portuguese talent by encouraging them to stay in their homeland with optimal conditions to carry out their projects, as well as to globalize the Spanish and Portuguese research system, attracting promising international researchers.

La Fundación ”la Caixa” this year has awarded 45 postdoctoral fellowships to researchers who will carry out their projects at leading universities and research centres in Spain and Portugal. In this way, the organization supports young talents and promotes innovative and high-quality research in the Iberian Peninsula. Among those awarded, Maria Apellaniz has been selected, who shall join the Navarrabiomed research centre of the Navarra Health Research Institute.
”La Caixa" Foundation offers the most important scholarship program among those promoted by private entities in Spain and Europe, both due to the number of scholarships offered and the variety of disciplines. The objective of these postdoctoral grants, to which the entity has allocated 11.28 million euros this year, is to retain local talent of excellence, as well as to attract foreign researchers, offering them competitive salaries and additional opportunities for training in cross-disciplinary skills.

Junior Leader Postdoctoral Program

Co-financed by the European Commission through the Marie Skłodowska-Curie COFUND Action, within the framework of Horizon 2020, this program is intended for the recruitment of excellent researchers, of any nationality, who wish to continue their research career in Spanish or Portuguese territory in the areas of health and life sciences, technology, physics, engineering and mathematics.
These postdoctoral fellowships, which have a duration of three years and an allocation of 305,100 euros per grant, include a complementary training program, with the aim of consolidating research skills and promoting an independent scientific career as an option for a professional future, dealing with topics such as leadership, conflict resolution or communication.
In this call, more than 700 people have applied to qualify for one of the fellowships. Of the 45 awardees, 20 are Spanish (from 14 provinces) and 25 foreign nationals (from 14 different countries). One of the awardees is pursuing her postdoctoral studies in Pamplona.
She is María Apellániz, born in Logroño in 1988, she has a degree in biochemistry from the University of Navarra (Pamplona) and a master's degree in biomedicine from the Autonomous University of Madrid (Madrid). In 2012, she joined the Hereditary Endocrine Cancer Group of the National Cancer Research Centre (Madrid) to complete her doctorate with another grant from the ”la Caixa” Foundation, during which time she worked on the identification of genetic variants that influence the response to treatment and toxicity in cancer patients. Subsequently, to expand her knowledge of human genetics, she completed a 3-year postdoctoral degree at McGill University (Canada). At the laboratory with Dr. Foulkes, she studied hereditary cancer syndromes and characterized the mechanisms involved in their pathogenesis. In 2020, she returned to Spain to join the Genomic Medicine Unit of Navarrabiomed (Pamplona), where she is responsible for analysing genomic data to discover genetic alterations underlying familial hypercholesterolemia and genetic markers associated with the response to statins. Her research has led to 37 publications in international journals, 11 of them as first author. Her goal is to understand the genetic differences underlying disease susceptibility and drug response, in order to benefit patients and promote customized medicine.
 
Project

Familial hypercholesterolemia (FH) is one of the most common hereditary diseases, with an estimated prevalence of 1 in 250 people worldwide. FH, which is characterized by considerably high blood levels of cholesterol from birth, confers an increased risk of premature cardiovascular disease (CVD) throughout life. Therefore, early diagnosis and suitable treatment substantially improve the CVD-free survival of these patients. However, the disease is still underdiagnosed and undertreated. The objective of this proposal is to apply a unique multidisciplinary strategy to personalize the diagnosis and treatment of patients with FH and their families, in order to reduce the morbidity and mortality of CVD episodes. This project will be carried out by integrating genomics, functional assays and clinical and lifestyle data. The results of this study may uncover new disease-causing genes/variants and genetic markers of statin response and CVD risk that could be used in clinical practice.
 

• The study is part of a national research initiative promoted by the Instituto de Salud Carlos III (Carlos III Health Institute) in which 17 health centres and nursing homes of 10 Autonomous Communities participate

Primary Health Care and the Navarrabiomed biomedical research centre, through their Clinical Trials Platform, have launched the observational study in the Regional Community ENE-COVID Senior on the third dose of the vaccine against COVID-19. The study is carried out within the framework of the national vaccination program and is aimed at generating knowledge about the immunization capacity acquired in elderly patients over time.
The initiative is part of national research conducted by the Carlos III Health Institute (ISCIII) in coordination with the ministries of Health and Science and Innovation, and entitled “Prospective Study to establish the immune status in the elderly after receiving a full course of vaccination ene-covid senior”. ENE-COVID Senior is a differentiated branch of the ENE-COVID national seroprevalence study (National Sero-Epidemiology survey of SARS-CoV-2 virus infection in Spain) being carried out since the onset of the pandemic.
 
Study characteristics

Specifically, the ENE-COVID Senior study will serve to establish the humoral and cellular immune status against SARS-CoV-2 in people aged 65 years or older having received the third dose of the vaccine for one year. Accordingly, the aim is to recruit a total of 1,600 patients coming from 17 centres from over 10 Autonomous Communities.
To do this, biological samples will be obtained and analysed from people who have received a full course of vaccination against Covid-19 at least 6 months before inclusion in the study. Samples will be taken at different times over 12 months. The participants come from nursing homes, Primary Health Care centres and hospitals, and are divided by age groups: 65-74, ≥75-84 and ≥ 85 years. The control group includes people under 65 years of age, mainly social and health workers from nursing homes and hospitals where the study is carried out.

In Navarra, the participation of patients is limited to the Barañain II health centre and the study is led by Dr. Itziar Blanco Platero, principal investigator and director of the aforementioned centre. “The objective is to generate knowledge as consistent as possible regarding the magnitude and duration of humoral and cellular immunity and to obtain information to establish future actions related to vaccination,” says Dr. Blanco.
The Clinical Trials Platform of Navarrabiomed has managed the start-up of the study through the Clinical Research Units and Clinical Trials Platform (SCReN) of the ISCIII, to which it belongs, providing the human and material resources necessary for its implementation. The choice of the Barañain II health centre also responds to the existing vaccination strategy in Navarra at the moment and the proximity of Navarrabiomed, an aspect that has facilitated the development and logistics necessary for study implementation.
 
Promotion of public health research in Navarra

To date and since the onset of the pandemic, the Clinical Trials Platform de Navarrabiomed has managed the initiation of more than thirty COVID-19 initiatives, two of them being multicentre trials led by research staff from Navarra and promoted by Navarrabiomed. The team is actively working so that researchers from the public health network of Navarra participate in Covid-19 clinical studies from which the group of patients of the Navarra Health Service-Osasunbidea can benefit. “Nowadays the decentralization of clinical trials is encouraged and Navarra is a community whose public health system is capable of hosting clinical trials with medicines, which is a promising for many Navarrese patients”, according to the Navarrabiomed Clinical Trials Platform.
 
News published in: https://www.navarra.es/es/noticias: https://www.navarra.es/es/noticias

La Unidad de Gestión de Navarrabiomed ha publicado hoy jueves, 22 de diciembre la relación provisional y definitiva de personas admitidas y excluidas del Programa de ayudas Navarrabiomed 2022 para cada una de las convocatorias: ayuda predoctoral y ayuda postdoctoral. Puede consultar y descargar a continuación la documentación correspondiente. 

• 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.

•    Today, Monday, November 14, is World Diabetes Day.

The Protein Crystallography and Structural Immunology Unit of Navarrabiomed has revealed a new molecular mechanism whereby autoimmune T cells are attracted by peptides (small protein fragments) present in the pancreas, something which interferes with its normal functioning and gives rise to the known insulin deficiency associated with type 1 diabetes. This alteration in the pancreatic tissue is one of the triggering causes of this autoimmune pathology, which in Navarra involves about 60 new diagnoses every year.

Specifically, the Navarrabiomed team, led by Jacinto López Sagaseta, has managed, with protein engineering techniques and X-ray crystallography, to identify contact that occurs between proteins of these autoreactive cells and of the pancreas involved in this autoimmune recognition. These findings have been recently published in "Frontiers in Immunology", an international scientific journal specialized in the field
The research work, carried out between 2020 and 2022, involved a close collaboration with the Pathogenesis and Treatment of Autoimmunity Group of the Hospital Clinic of Barcelona – IDIBAPS of Barcelona, led by Dr. Pere Santamaria, and with funding from the Ministry of Science and Innovation, the Generalitat de Catalunya, the Carlos III Health Institute, ERDF and the Canadian Institutes of Health Research (Instituts de recherche en santé du Canada).
 

Research development
X-ray crystallography is a scientific discipline established for the first time in Navarra by Jacinto López Sagaseta, a researcher who in previous periods has already fronted studies in the field of structural biology and immunology at international centres such as the University of Chicago and GSK Vaccines. To carry out these studies, the Unit's team uses cellular “factories” specializing in the production of proteins. Once produced, these proteins are isolated from the rest of the components present in the production with chromatographic techniques, to later literally crystallize them. These crystals formed by the proteins of interest allow the structural study and the definition of the fingerprint of this autoimmune interaction, and with atomic precision, since X-ray diffraction allows molecules (such as proteins) to be observed with Angstrom accuracy (one Angstrom is equivalent to one ten millionth of a millimetre), hence known as atomic resolution. In this way, the studies carried out by the researchers have made it possible to reveal, one by one, the contacts that these immune system cells (T cells) establish between their proteins and peptides present in the pancreas. This molecular and structural recognition is key to the activation of these cells, their subsequent adverse effect on the pancreas and the resulting insulin deficiency.

These findings represent a significant advance in the knowledge of autoimmune diseases such as type 1 diabetes. “The results reveal previously unknown mechanisms of interaction between cells of the immune system and the pancreas, which could lead to the design of new pharmacological therapies,” says López Sagaseta.

2,218 patients diagnosed with type 1 diabetes in Navarra
 In May of this year, the number of living patients diagnosed with diabetes in Navarra was 42,004 (6.5% of the total population), of which 2,218 are patients diagnosed with type 1 Diabetes Mellitus (DM) and 39,786 with type 2 Diabetes Mellitus. 

 

Photo caption: Team of researchers at Navarrabiomed who have participated in the study. 
From left to right: Sergio Morales, Adela Rodríguez, Nerea Ugidos, Jacinto López, Alejandro Urdiciain and Elena Erausquin. Not appearing in the photo: Gilda Dichiara.
 
 

• The team has analysed the role of fatty acid metabolism in the development of metastatic melanoma.

Navarrabiomed's Cancer Signalling Unit has led an investigation, in close collaboration with researchers from the Cima University of Navarra, which presents new therapeutic targets in patients with melanoma, a type of skin cancer with a special ability to produce metastases. The study makes it possible to advance in the development of new therapies aimed at preventing the development of secondary tumours in vital organs such as the liver or lungs.

Scope of the research 

Research has focused on the study of the so-called Circulating Tumour Cells (CTCs), responsible for haematogenous metastases. This type of metastasis is generated from tumour cells that leave the primary tumour, go into the bloodstream and spread throughout the organism/body. Some of these CTCs are able to settle in internal organs such as bone, lung, liver or brain, forming secondary tumours or metastases. Metastases cause 90% of cancer mortality. Current knowledge of these tumour cells, and the process by which they adapt to survive in the bloodstream, is very limited and studies such as the one presented gain relevance. 

Specifically, the team has discovered that CTCs reorganize fatty acid metabolism in order to survive and this has made it possible to identify two possible therapeutic targets, CRAT and CROT genes, which regulate CTC survival. They have further identified two drugs, ranolazine and thioridazine, the use of which is already approved in humans and which block fatty acid metabolism to reduce the ability of CTCs to generate haematogenous metastases. 

“The identification of these two therapeutic targets is encouraging. Use of ranolazine and thioridazine as a cancer treatment has great potential. Today we are studying its possible combination with other drugs that are currently administered to patients with metastatic melanoma to increase their effectiveness”, as noted by Imanol Arozarena. 

This study highlights the extraordinary ability of tumour cells to adapt to different microenvironments and contributes to an increasingly relevant field of research on the role of lipid metabolism in the development of metastatic diseases. 
It is also the first study that associates the fatty acid metabolism that occurs in peroxisomes (small cellular organelles) with metastasis. Until now, the scientific community had not paid attention to peroxisomes and we trust that our study will serve to focus on the cellular functions of these organelles in future cancer research.

Public-private partnership 

The study has been carried out from the Cancer Signalling Unit of Navarrabiomed, fronted by Imanol Arozarena Martinicorena, and is part of the doctoral thesis of the centre's pre-doctoral researcher of the, Irene Lasheras Otero. The team has worked in close collaboration with the Oncogenes and Effector Targets group directed by Silve Vicent, and which is part of the Solid Tumours Program of the Cima University of Navarra. Other Navarrabiomed units such as Proteomics and Bioinformatics have also participated.

The results have been published in Journal of Investigative Dermatology and, are included among the scientific output of the Institute of Health Research of Navarra (IdiSNA), a public-private association for the promotion of biomedical research in the Autonomous Community in which both research centres participate. The Navarrabiomed team has further announced the research work at the “Metabolism Symposium” of the University of California San Francisco (USA) held on June 17 and at the “Metabolism and Cancer” Conference, organized by the European Association for Cancer Research (EACR), which recently took place in Bilbao from the 11th to the 13th of October.

The Government of Navarra and the Ministry of Economy and Business, through the Carlos III Health Institute-ERDF, have financed this study. 
Incidence 

In 2021, 6,100 new cases of metastatic melanoma were diagnosed in Spain, causing the death of 90% of all those affected by melanoma. Worldwide, this type of cancer accounts for 1.7% of the total oncological cases detected, although its incidence rate is growing at a high pace compared to other more common tumours. These figures put the focus on prevention and, therefore, on the main cause of skin cancer: unprotected exposure to ultraviolet radiation from the sun and also from UV tanning beds/booths.

In the last decade, mortality from metastatic melanoma has been reduced by 30% thanks to the emergence of targeted therapies and immunotherapies. Studies such as the one presented will contribute to progress in reducing this rate, as well as in improving clinical treatments.  
 

Photo caption: From left to right. Ana Olías (NB), Iker Feliu (Cima), Silve Vicente (Cima), Irene Lasheras (NB), Imanol Arozarena (NB), Paula Aldaz (NB) and Marta Redondo (NB).

Con motivo de su décimo Aniversario, Navarrabiomed presenta la exposición "De la célula al paciente. 10 Años avanzando juntos / Zelulatik pazientera. 10 urte elkarrekin lanean", en el marco de las Semanas de la Ciencia, la Tecnología y la Innovación de Navarra 2022. La muestra, accesible en castellano y euskera, está dirigida al personal sanitario, investigador y público general.

Se trata de una muestra en la que se destacan, con un enfoque divulgativo, los retos y oportunidades que supone la integración de la investigación biomédica en la práctica clínica del sistema público de salud a lo largo de estos diez años.

Son 9 piezas científicas en formato de esculturas sostenibles de cartón que exponen avances en investigación biomédica, así como los retos y desafíos a los que se enfrenta la investigación en salud. Está dirigida al personal sanitario y al público en general, y busca acercar la ciencia a la sociedad a través de nuevos formatos interactivos con realidad aumentada. Asimismo los temas que se abordan son:

• Alzhéimer: el reto del  diagnóstico precoz
• Cristalografía: la ciencia que estudia los cristales
• Actividad física: un escudo protector
• Enfermedades de las válvulas cardíacas: la epidemia silenciosa
• Medicina genómica: adelantarse al futuro
• Inmunoterapia: un gran aliado frente al cáncer
• Bacterias: aliadas o enemigas 
• Perspectiva de género: una nueva mirilla en investigación 
• Ciencia de datos: descifrar el código de la vida 

Para disfrutar de todos los contenidos es necesario descargar gratuitamente la app de Navarrabiomed (disponible para Android y para iOS).

Este proyecto ha recibido financiación del Departamento de Universidad, Innovación y Transformación Digital del Gobierno de Navarra en la convocatoria de Ayudas al Fomento de la Cultura Científica, la difusión de la I+D+i realizada en Navarra y al fomento de las vocaciones STEM COSMOS 2022 y 2023. El diseño conceptual y visual y los contenidos de la exposición han sido realizados por la Unidad de Comunicación y Diseño de Navarrabiomed. La empresa iAR (Industrial Augmented Reality) ha sido la encargada de realizar la programación en realidad aumentada y Tresatres, la impresión de las piezas.
 

Exposición itinerante

En 2023, la exposición adquirirá un carácter itinerante, y se ubicará en diferentes espacios expositivos de la Comunidad Foral con el fin de que llegue a la ciudadanía navarra.

• Del 24 de enero al 9 de febrero: Planetario de Pamplona.
• Del 11 al 26 de febrero: Casa de cultura Fray Diego de Estella / Lizarra. 
• Del 4 al 28 de mayo: Casa de Cultura de Sangüesa / Zangoza.
• Del 19 de septiembre al 9 de octubre: Centro Cultural Iortia de Alsasua/Altsasu
• Del 30 de octubre al 10 de diciembre: Palacio del Condestable de Pamplona /Iruña 

Javier Sánchez Ruiz de Gordoa, predoctoral researcher of the Neuroepigenetics Unit of Navarrabiomed, will be sitting his viva for his doctoral thesis from the Public University of Navarra next Thursday, July 14th at 4 pm in the Assembly Hall of Navarrabiomed. 

The doctoral work, which is entitled “Progressive Supranuclear Palsy: clinical-pathological correlation and approach to the pathogenic role of microglia”, has been developed at the University Hospital of Navarra and Navarrabiomed under the direction of Elena Erro Aguirre, Maite Mendioroz Iriarte and Mª Victoria Zelaya Huerta.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease which manifests clinically as an atypical Parkinsonism. The deposits of tau protein in neurons and glial cells are its pathological basis and is the most common primary tauopathy. The ultimate diagnosis is neuropathological and, in recent years, progress has been made in the definition of more sensitive and specific clinical diagnostic criteria and in the identification of potential biomarkers.
The hypothesis of this doctoral thesis is that there is a correlation between the different density and distribution of tau protein deposits in the different structures of the brain and the phenotypic expression of PSP. In turn, this clinical expression could be influenced by the interaction of the tau protein with other neuronal protein deposits. It is further proposed that the activation of microglia may play a role in the pathophysiology of the disease.

Research development and results

For research development, three works have been prepared that form a thematic unit. In the first of them, a descriptive cross-sectional study of the clinical-pathological characteristics of the series of 34 cases of PSP of the Navarrabiomed biobank, patients who died between 2005 and 2017, is carried out, and the deposits of the tau protein are compared between the clinical phenotypes resulting from the retrospective application of different clinical diagnostic criteria.  In the second work, cases presenting a coexpression of the tau protein and alpha-synuclein are described and the distribution of the deposits in the substantia nigra (SN) and the Locus Coeruleus is studied using double immunohistochemistry and immunofluorescence techniques. In the third work, a descriptive observational study is carried out comparing the expression of a candidate gene, TREM2 (Triggering Receptor Expressed in Myeloid cells type 2), related to inflammation and microglial activation, in samples of SN from 24 cases of PSP and controls without neuropathology, and the correlation between gene expression and tau protein deposits is analysed.

The results obtained show that the application of the new criteria for the diagnosis of PSP of the Movement Disorders Society decreases the phenotypic variability and, together with other limiting factors such as sample size, conditions the loss of differences in the cortical tau load identified between the resulting phenotypes after the application of other previous classifications. On the other hand, the coexpression of alpha-synuclein (Lewy bodies) and tau protein deposits in the same dopaminergic neurons of the SN of patients with PSP is described for the first time. In addition, it is identified that the TREM2 gene is overexpressed in the SN of patients with PSP with respect to controls and that this expression correlates directly with tau protein deposits in the SN suggesting that TREM2-mediated microglial activation participates in the pathophysiology of the disease. 

Dissemination of results 

The work carried out has led to several scientific publications: in 2022, in the journal Frontiers in Neurology, Is the phenotype designation by PSP-MDS criteria stable throughout the disease course and consistent with tau distribution?, in 2020 in the journal Movement Disorders, Microglia-Related Gene Triggering Receptor Expressed in Myeloid Cells 2 (TREM2) Is Upregulated in the Substantia Nigra of Progressive Supranuclear Palsy and in 2015 in the journal Frontiers in Neuroanatomy, Midbrain catecholaminergic neurons co-express α-synuclein and tau in PSP. 

In addition, the preliminary and definitive results have been disseminated at several national and international congresses in the area of Neurology and Pathological Anatomy such as the annual meeting of the Spanish Society of Neurology (in 2013, 2017 and 2019), the International Conference on Frontotemporal Dementias in 2016, the European Congress of Neuropathology (in 2016 and 2018) or the annual meeting of the MDS in 2018.
 

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.