Research

About

The Clinical Genomics Research Group is part of the Genetics Department at Germans Trias Hospital (HUGTiP) in the North Metropolitan Area of Barcelona (LCMN). The group has several important responsibilities, including diagnosing and monitoring patients with hereditary diseases, providing genetic counseling to patients and their families, and conducting genetic tests to determine the genetic cause of these diseases. The group is dedicated to improving patient management by considering all aspects of patient care, including emotional, social, religious, and physical dimensions.

The group is also focused on increasing the cost-effectiveness of genetic testing and enhancing their knowledge of the genetic bases of various diseases, both monogenic and poligenic diseases. To achieve this goal, they are actively developing new genomic techniques to analyze germline and somatic variants at both RNA and DNA levels and implementing a new technology for massive genotyping to stablished new pooligenic risk scores. Additionally, the group is participating in developing new methodologies to determine the status of known pharmacogenomics biomarkers by taking part in PHARMA-IMPCAT and establishing the Pharmacogenomics Unit at HUGTiP.

Furthermore, the group is a member of the Spanish Reference Center (CSUR) for adult patients with Phakomatoses (Neurofibromatoses, Schwannomatosis, Tuberous Sclerosis, and Von-Hippel Lindau diseases), which is a part of the European Network of Reference Centers (ERN) GENTURIS. The group is working on developing personalised medicine for this group of patients and developing new clinical guidelines that also take into account patients' emotional and social needs. They are also discovering new prognostic biomarkers, understanding the role of genomic alterations in the development of disease-associated lesions, and implementing various gene therapy strategies to cure these diseases.

Keywords: Neurofibromatosis, schwannomatosis, genetic testing, clinical genomics, clinical genetics, gene therapy, phakomatosis, rare diseases.

Clinical Genomics Research

Group Leader

  • Ignacio Blanco Guillermo

    Ignacio Blanco Guillermo

    Ignacio Blanco is the coordinator of a CSUR (reference unit) of the Sistema Nacional de Salud and the national coordinator of the European Network of Reference Centers (ERN) GENTURIS, a network for all patients with any of the rare syndromes of genetic predisposition to the development of tumours (GENTURIS). In addition, he is a member of the Advisory Committee on Minority Diseases (CAMM) from the Government of Catalonia and advisor to the Spanish Ministry of Health in the area of Genetics.

    Contact: iblanco.germanstrias(ELIMINAR)@gencat.cat
    ORCID: 0000-0002-7414-7481

    Extended biography (as narrated by Dr Blanco):

    In 2009 I enrolled in the Germans Trias i Pujol Research Institute (IGTP) to be in charge of the genetic diagnostics activity of the Hereditary Cancer program. Since 2015, I am the coordinator of genetic diagnosis in the Spanish Reference Center (CSUR) on Phakomatoses. In the last years, our group has been incorporated in the GENTURIS (European Reference Network of rare genetic tumor risk syndromes) and has been recognized as a consolidated group of Neurofibromatosis by Generalitat de Catalunya (SGR2018, SGR2022). In addition, I also participate in the Catalan Health Institute's XIGENICS program, and collaborate closelly with the Institut Català d'Oncologia (ICO), and Dr. Lázaro.

    During 2009-2019, I had been developing all my activity of diagnosis, innovation and research within the Hereditary Cancer Group, led by Dr Serra. In 2019, I moved to Hospital Universitary Germans Trias & Pujol (HUGTP) to coordinate the Clinical Genomics Unit, and I was recognized as emerging principal investigator at IGTP. Since then, a translational research activity centered in CSUR patients has been going on. As a result, different works have been published: 1) we used for the first time antisense oligomers as a potential therapeutic strategy for patients with NF2 (PMID: 23188051, 36420221); 2) we deepened in the use of genomic techniques to perform differential diagnosis of Neurofibromatoses (PMID: 25739810) and also to improve the genetic counselling (PMID: 35121649); and 3) we studied the molecular pathogenesis of NF2 skin plaques, useful to establish an early diagnosis (PMID: 29322178, 35490384): amd 4) we have been able to improve the NF2 genetic score published by the UK reference center (Halliday 2017) to predict the prognosis of patients carrying splicing and mosaic variants (PMID: 34348961).

    In the area of innovation, I developed, validated and implemented to the routine diagnostics activity, a custom NGS panel of 135 genes of hereditary cancer, the I2HCP (PMID: 28051113) and also to genetically diagnose RASopathies and related syndromes (PMID: 31573083). This development technologically transformed the two genetic diagnosis units where it has been implemented (the HUGTP and ICO), and allowed us to join forces to homogenize the techniques used in other centers, such as the Vall d'Hebron University Hospital, among others.

    Currently, more than 8000 patients visited at the ICO or at our center have been genetically diagnosed with this technological development. In addition, I have collaborated in the search of new genes associated to Shcwannomatosis (PMID: 34747535) or new genomic analysis to improve the genetic testing (PMID: 35569879, 32561899, 33983414, 36818284).

    Currently, thanks to my experience in genetic testing on Neurofibromatosis and related disorders, I am co-leading togehter wiht Dr. Plotkin (MGH, USA) the ClinGen-NIH International expert panel of variant curation for these group of diseases (NF-SWN VCEP) and also coordinating the international consortium EURONET-NF to improve the molecular testing of this group of disorders.

    Finally, in order to generate a non-perishale NF2 cellular model to test the different therapeutics approaches developed in the laboratory, we have generated induced pluripotent cells (iPSC) harboring the germline and the somatic variant (NF2(-/-))(Catasús et al, in revision) as well as we collaborated to generate NF1 iPSC (PMID: 35172160, 30713041).

    In the last 5 years, 4 of which as an associate principal investigator at the Germans Trias i Pujol Research Institute (IGTP), I have achieved funding to develop different lines of research and lead the aforementioned consortia through competitive projects at regional, national and international level and from different national and international patient associations for a total value of more than €2,300,000. We participate in the ISCII programs "Data Science Program IMPaCT-Data, call 2021," and "iPHARMGx", call 2022. In addition, I got funding for hire a PhD Student, Núria Catasús, who defended her Thesis on May 2022 and I am on charge of formation on genetics of clinical residents at HUGTP.

    We have also disseminated this work and other scientific achievements through news on the research institute's website, scientific dissemination conferences held at our center, as well as regular collaborations with patient associations, mainly the Association of Patients with Neurofibromatosis (AANF) and the Children's Tumour Foundation (CTF) in the conferences they organize.

  • Elisabeth Castellanos Pérez

    Elisabeth Castellanos Pérez

    Elisabeth Castellanos co-leads together with Scott Plotkin (Massachusetts General Hospital, USA) the Neurofibromatoses and Schwannomatosis Variant Curation Expert Panel (NF-SWN VCEP) at ClinGen-NIH, aimed at establishing clinical guidelines for classifying genetic variants of these diseases. The panel was funded by the National Institutes of Health (NIH) with a U24 grant. Castellanos also coordinates the international consortium EURONET-NF, which has the objective of improving diagnostic molecular testing for this group of disorders. She collaborates closely with Children's Tumor Foundation (CTF) and was invited to serve as a session co-chair at the CTF 2023 NF Conference in Scottsdale, USA, to update on the advances of the NF-SWN VCEP and also to the 2024 NF Global Conference to chair a gene therapy session. In 2023, Castellanos renewed her P-FIS grant and also got a Sara Borrell fellowship for the 2024-2026 period. Finally, she is collaborating with Plotkin to develop new genetic therapies for neurofibromatosis type 2.

    Contact: Ecastellanosp.germanstrias(ELIMINAR)@gencat.cat
    ORCID: 0000-0002-8133-5325

Research lines

Management of phakomatoses patients

Improving the management of phakomatoses patients considering not only clinical diagnosis but also emotional, social, religious and physical dimensions that could impact patients with these rare diseases.

Development and implementation of new genomic techniques for genetic diagnosis of hereditary diseases

Increasing the cost-effectiveness of genetic testing and our knowledge of the genetic basis of some hereditary diseases (mostly phakomatoses and hereditary renal diseases). The group is focusing research on developing new genomic techniques, both at RNA and DNA levels, to analyse both germline and somatic variants.

Personalised medicine for neurofibromatoses

Developing personalised medicine for neurofibromatoses and schwannomatosis patients, which include the discovery of new prognostic biomarkers, understanding the role of patient's genomic alterations in the development of disease-associated lesions and the implementation of different gene therapy strategies as a potential treatment for this group of diseases.

Genetic susceptibility to illness

Developing strategies to evaluate genetic individual susceptibility to illness. This will allow for the implementation of personalised and precision medicine in different areas of the Can Ruti campus.

Active projects

EURONET- NF: European Network for improved molecular diagnostics of the NeuroFibromatoses - schwannomatoses and related disorders

PI: Elisabeth Castellanos
Funding agency: European Joint Program for Rare Diseases (EJP -RD) a través de "Proyectos de colaboración internacional" del Instituto de Salud Carlos III (AC22/00033)
Agency code: EJPRD22-084
Duration: 01/06/2023 - 31/05/2026

Developing NF2 iPSC-cell models for the use of antisense oligonucleotides as a personalized therapy for Neurofibromatosis Type 2 patients

PI: Elisabeth Castellanos
Funding agency: Children's Tumor Foundation
Agency code: CTF-2022-05-005
Duration: 01/02/2023 - 31/01/2024

Suppression of NF1 Nonsense Mutations by RNA-guided RNA Pseudouridylation

PI: Elisabeth Castellanos, Yi Tao, Conxi Lazaro, Pedro Marais
Funding agency: Gilbert Family Foundation
Duration: 01/01/2022 - 31/12/2024

Plataforma de medicina de precisió, una eina necessària per la transformació del procés assistencial

PI: Ignacio Blanco
Funding agency: HUGTP
Duration: 01/01/2023 - 31/12/2026

Desarrollo de una estrategia de medicina personalizada para la NF2-SWN: mejora del diagnóstico genético, y evaluación de terapias génicas a nivel de RNA en un modelo de iPSCs de schwannomas

PI: Elisabeth Castellanos
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: PI23/00412
Duration: 01/01/2024 - 31/12/2026

Mejora del diagnóstico genético del cáncer hereditario y enfermedades hereditarias con predisposición a desarrollar tumores

PI: Elisabeth Castellanos
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: CD23/00038
Duration: 01/01/2024 - 31/12/2026

Genomic epidemiology of SARS-CoV-2 in Catalonia: virological vigilance and control of outbreaks

PI: Marc Noguera Julián, Elisa Martró Català
Agency code: 1162/U/2021
Duration: 01/06/2021 - 31/05/2024

A patient centered research: awareness of patientsneeds, clinical phenotyping and molecular pathogenesis in Neurofibromatosis type 2

PI: Elisabeth Castellanos
Funding agency: Fundació La Marató de TV3
Agency code: P126/C/2020
Duration: 01/04/2021 - 31/03/2024

The human genetic and immunological determinants of the clinical manifestations of SARS-CoV-2 infection: Towards personalised medicine

PI: UNDINE Consortium; Collaborator: Ignacio Blanco
Funding agency: Horizon Europe
Duration: 01/09/2022 - 31/12/2026

Consolidation of WGS and RT-PCR activities for SARS-CoV-2 in Spain towards sustainable use and integration of enhanced infrastructure and processes in the RELECOV network

PI: Inmaculada Casas; Collaborator: Ignacio Blanco
Duration: 01/01/2023 - 31/12/2026

Proyecto iPHARMGx: Estudio colaborativo nacional para evaluar la efectividad y eficiencia de la implementación de biomarcadores farmacogenéticos mediante una estrategia de genotipado anticipado en el SNS

PI: Alberto M Borobia Perez
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: iPHARMGx
Duration: 01/01/2023 - 31/12/2025

Grups de Recerca Reconeguts per la Generalitat de Catalunya, GRC (Grup de Recerca Consolidat)

PI: Ignacio Blanco
Funding agency: Generalitat de Catalunya
Agency code: 2022 SGR 967
Duration: 01/01/2023 - 31/12/2025

Past projects

Desarrollo de una estrategia de medicina personalizada para la NF2: mejora del diagnóstico genético, la evaluación de la calidad de vida y generación de un modelo de schwannomas a partir de iPSCs

PI: Elisabeth Castellanos, Ignacio Blanco
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: PI20/00215
Start date: 01/01/2021
End date: 31/12/2023

NF Variant Curation Expert Panel (VCEP)

PI: Elisabeth Castellanos
Funding agency: National Institutes of Health (NIH) ClinGen Variant Curation Expert Panel (VCEP)
Start date: 27/12/2021
End date: 30/12/2023

Programa de Ciencia de Datos (IMPaCT-Data), Infraestructura de Medicina de Precisión asociada a la Ciencia y Tecnología (IMPaCT)

PI: Alfonso Valencia Herrera
Funding agency: Alliance for Education Solutions (AES)
Agency code: PI20/00215
Start date: 01/01/2021
End date: 31/12/2023

Scientific publications

Catasús N, Rosas I, Bonache S, Negro A, Torres-Martin M, Plana-Pla A, Salvador H, Serra E, Blanco I, Castellanos E. Antisense oligonucleotides targeting exon 11 are able to partially rescue the NF2-related schwannomatosis phenotype in vitroMol Ther Nucleic Acids. 2022 Dec 13;30:493-505. DOI: 10.1016/j.omtn.2022.10.026.

Garcia B, Catasus N, Ros A, Rosas I, Negro A, Guerrero-Murillo M, Valero AM, Duat-Rodriguez A, Becerra JL, Bonache S, Lázaro Garcia C, Comas C, Bielsa I, Serra E, Hernández-Chico C, Martin Y, Castellanos E, Blanco I. Neurofibromatosis type 1 families with first-degree relatives harbouring distinct NF1 pathogenic variants. Genetic counselling and familial diagnosis: what should be offered?J Med Genet. 2022 Oct;59(10):1017-1023. DOI: 10.1136/jmedgenet-2021-108301.

Catasús N, Garcia B, Galván-Femenía I, Plana A, Negro A, Rosas I, Ros A, Amilibia E, Becerra JL, Hostalot C, Rocaribas F, Bielsa I, Lazaro Garcia C, de Cid R, Serra E, Blanco I, Castellanos E. Revisiting the UK Genetic Severity Score for NF2: a proposal for the addition of a functional genetic componentJ Med Genet. 2022 Jul;59(7):678-686. DOI: 10.1136/jmedgenet-2020-107548.

Castellanos E, Rosas I, Negro A, Gel B, Alibés A, Baena N, Pineda M, Pi G, Pintos G, Salvador H, Lázaro C, Blanco I, Vilageliu L, Brems H, Grinberg D, Legius E, Serra E. Mutational spectrum by phenotype: panel-based NGS testing of patients with clinical suspicion of RASopathy and children with multiple café-au-lait maculesClin Genet. 2020 Feb;97(2):264-275. DOI: 10.1111/cge.13649

Castellanos E, Plana A, Carrato C, Carrió M, Rosas I, Amilibia E, Roca-Ribas F, Hostalot C, Castillo A, Ros A, Quer A, Becerra JL, Salvador H, Lázaro C, Blanco I, Serra E, Bielsa I. Early Genetic Diagnosis of Neurofibromatosis Type 2 From Skin Plaque Plexiform Schwannomas in ChildhoodJAMA Dermatol. 2018 Mar 1;154(3):341-346. DOI: 10.1001/jamadermatol.2017.5464.

publications of the group

These are five highlighted publications by the group. A complete list of publications by the group members will soon be available on this page.

Additional information

Collaborative Networks

  • CSUR de Facomatosis ICO-HGTP-IGTP. Dr. Blanco is the coordinator or Spanish Reference Center.
  • European Network of Reference Centers (ERN) GENTURIS (syndromes with predisposition to rare tumors).
  • NF-EURONET: European network to improve genetic testing for Neurofibromatosis, Schwannomatosis and related syndromes.
  • Neurofibromatosis and Schwannomatosis Variant Curation Expert Panel (NF_SWN VCEP): International network recognized by National Health Institute (NIH) - ClinGen program to stablish gene-specific ACMG/AMP classification criteria for these diseases
  • Grup de Recerca en Neurofibromatosis (GRNF) 2021 SGR 00967: Multidisciplinary Neurofibromatosis Research Group recognized by the Government of Catalonia.
  • XIGENICS: comprehensive genetics network of the Institut Català de la Salut to implement genomics medicine at ICS's hospitals.
  • Can Ruti COVID sequencing HUB: HGTP - IGTP- IRSICaixa network to characterize SARS-2-Covid variants detected in our population.
  • Children's Tumor Foundation Europe (CTF-Europe): The Children's Tumor Foundation Europe's mission is to drive research, expand knowledge, and advance care for the NF community.

National and international partners

  • Scott Plotkin, MD, PhD at Massachusetts General Hospital to participate in gene therapy approaches for NF2.
  • Dr Piotrowski at Medical University of Gdanskv: Schwannomas' characterization and discover new genes to induce these kind of tumors.
  • Dr Lázaro at Hereditary Cancer Program of Catalan Institute of Oncology (ICO) to improve genetic diagnostics tools and NF research, and common research projects
  • Dr Jordi Llorens, at Facultat de Medicina i Ciències de la Salut (UB), together with Otorhinolaryngology Service at HUGTiP to study the pathogenesis of vestibular Schwannomas and hearing loss.
  • The Barcelona Neurofibromatosis Group (BCN_NF Group). The group is composed by different groups that collaborate together in the field of the Neurofibromatoses: the group of Dr. Conxi Lázaro who initiated the first NF Group at mid '90s; the group of Dr. Serra (Hereditary Cancer Group at IGTP) with huge experience in study the contribution of somatic variants in the development of NF tumors and also in the development of iPSC-based models for study NFs; the group of Dr. Cleofé Romagosa (Department of Pathology, Vall d'Hebron Hospital) pathologist specialist in sarcomas and expert in tumors of the PNS associated to NFs, and our group.

Comittees and advisory boards

Dr Blanco is advisory board of:

  • Associación Espanyola de Afectats por la Neurofibromatosi (AENF)
  • Associació Catalana de Neurofibromatosi (AcNefi)
  • Member of the Advisory Council for Minority Diseases of Departament de Salut de la Generalitat de Catalunya
  • Member of the Advisory Council of the National Commission for Assisted Human Reproduction (CNRHA)
  • Member of the Advisory Committee of the Spanish Federation of Rare Diseases (FEDER)
  • Advisor to the Spanish Ministry of Health in the area of Genetics

Theses

Title: Refining prognosis capacity and implementing principles of personalized therapies for Neurofibromatosis type 2
Author: Núria Catasús Segura
University: Universitat de Barcelona
Date of defense: 31/05/2022
Qualification: Cum Laude

News

Can Ruti celebrates a Rare Disease Day symposium highlighting the importance of research to help patients

On Thursday 29 February, the Germans Trias Hospital hosted the 'International Rare Disease Day Symposium'. Health professionals and researchers from the Hospital and IGTP discussed their work in advancing the field of rare diseases. Representatives from patient associations of these diseases also participated.

- Research, Projects

IGTP will coordinate a European project to improve the diagnosis and treatment of neurofibromatoses

Researchers from the Clinical Genomics Group at Germans Trias i Pujol Research Institute (IGTP) and the Genetics Service at Germans Trias i Pujol Hospital (HUGTiP) will coordinate the project EURONET-NF, which aims to improve genetic diagnosis for patients with neurofibromatoses and schwannomatosis (NF-SWN). The project, which involves 6 countries, has been awarded around €1.6 million in funding by the European Union for the next 3 years.Researchers from the Clinical Genomics Group at Germans Trias i Pujol Research Institute (IGTP) and the Genetics Service at Germans Trias i Pujol Hospital (HUGTiP) will coordinate the project EURONET-NF, which aims to improve genetic diagnosis for patients with neurofibromatoses and schwannomatosis (NF-SWN). The project, which involves 6 countries, has been awarded around €1.6 million in funding by the European Union for the next 3 years.

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