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IDIBAPS Rosselló, 149-153 08036 Barcelona

Editorial board

IDIBAPS Scientific Coordination Office

Art direction & graphic design

Marc Montalà www.marcmontala.com

Cover photo

© Irene Portolés

© IDIBAPS 2019 http://creativecommons.org/licenses/by-nc-sa/4.0/

ANNUAL

SCIENTIFIC REPORT

2018

INDEX

08 Foreword IDIBAPS

Director’s foreword About IDIBAPS Staff Research and innovation outputs Funding Institutional projects Scientific facilities Training Communication and public engagement News

56 Area 1

Biological aggression and response mechanisms

94 Area 2

Respiratory, cardiovascular and renal pathobiology and bioengineering

152 Area 3

Liver, digestive system and metabolism

218 Area 4

Clinical and experimental neuroscience

276 Area 5

Oncology and haematology

332 Transversal research groups

343

Team and group leaders index

ANNUAL

SCIENTIFIC REPORT

2018

FOREWORD IDIBAPS

© Patricia Solé

Director’s foreword

It is a great privilege and satisfaction to present in this 2018 Annual Report the activities and outstanding achievements of all the people working at IDIBAPS. Our scientific contributions are improving the understanding of the diseases we study and are changing the way we practice medicine. Our commitment to society stimulates us to spread this knowledge and these values to citizens of all ages.

From the institutional perspective, I would like to highlight the work to culminate our new strategic plan (2018-2022), which was discussed by a broad representation of the research and management communities. An analysis of the current situation of biomedical research and the social and scientific challenges that we all face have led us to define the strategic objectives and actions that will serve as a roadmap for addressing the complex situation in which we work. Major effort will be dedicated to consolidating and improving excellence in translational research, attracting and retaining talent, particularly with the crucial task of generational renewal and the need to promote the clinician scientist career. We need to reinforce innovation and technology translation to attain the highest impact in clinical practice and optimize the resources to achieve the desired objectives. Next year will be crucial for the institutional fusion of IDIBAPS and Fundació Clínic per a la Recerca Biomèdica (SUMA project), which should facilitate research in the Clínic Barcelona Campus.

This year, the Board of Governors accepted the nomination of Prof José María Mato as new President of the Scientific Advisory Board (SAB), replacing Prof Jesús Ávila, who remains as member of the SAB. We welcome Prof Amparo Cano, Full Professor of the Autonomous University of Madrid and researcher at the Institute of Biomedical Research “Alberto Sols”, and Dr Pura Muñoz, ICREA researcher at Pompeu Fabra University, as new members of the SAB,replacing Dr Guadalupe García-Tsa, Roberto Grozman, Bartolome Celli and Miguel Ángel Pozo. We are extremely grateful to all of them for their contributions to the success of IDIBAPS. The SAB is instrumental in guaranteeing the high standards in the scientific goals of the Institute.

This year, the Direction and Administration of IDIBAPS also made an extra effort to provide all the key performance Indicators (KPIs) required by the Instituto de Salud Carlos III Health Institute (ISCIII) to renew our accreditation as . In addition, we compiled all the documents requested by Fundación Científica de la Asociación Española Contra el Cáncer (FC-AECC) to obtain the new accreditation as a recognized center in Cancer Research.

The major strength of IDIBAPS continues to be the intense and excellent scientific production of its researchers, who in 2018 have maintained the high level reached in previous years. Of more than 1,100 original articles published, almost 350 (31%) were in first-decile journals and 170 (16%) in top journals (impact factor over 10). Our researchers also published 314 reviews and editorial articles, which underscores the high level of international leadership of our researchers. These excellent contributions encompass a broad spectrum of activities, from novel discoveries that are changing treatment standards to basic studies that improve understanding of the diseases in question. It would be difficult to summarize the tremendous amount of contributions, but some examples worthy of mention include the seminal contributions in the treatment of hepatocellular carcinoma, nosocomial pneumonia, cardiac arrhythmias, and the use of stem cells for the treatment of chronic inflammatory bowel disease. They have also provided important novel information on the evolution of diseases such as autoimmune encephalitis and hepatitis C. From a more basic perspective, our scientists have developed animal models for understanding liver fibrosis and treatment of cirrhosis, and have elucidated the genome-wide epigenomic modifications that shape the development of chronic lymphocytic leukemia. I should also mention the 39 international clinical guidelines, in which our researchers have participated, setting the standards for diagnostic procedures and therapeutic management of a variety of diseases–clear proof of the institutional spirit and commitment to translate research into clinical practice.

To sustain this production activity, IDIBAPS researchers have raised a significant amount of national and international funds, with more than 200 new projects from competitive and private sources. Indeed, IDIBAPS appears to be one of the national institutions with a better success rate in the ISCIII and H2020 programs. In 2018, two groups from IDIBAPS obtained a prestigious ERC Synergy grant in collaboration with two groups from CNAG-CRG to participate in the international project of the Human

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Cell Atlas and study the chronic lymphocytic leukemia at a single cell level. Three groups obtained the highly competitive grants from the La Caixa Health program, two groups participate in major European consortiums funded by the FC-AECC, together with charities from the UK (CRUK) and Italy (AIRC) to study hepatocellular carcinoma and early manifestations of hematological disorders, and one group obtained a PO1 grant from the National Institutes of Health of the USA.

A special extraordinary achievement that deserves our deepest gratitude is the commitment and generosity of more than 1,600 donors raising more than one million euros, which has made it possible to initiate the immunotherapy program with the innovative CAR-T cell strategies in the project that we have named the ARI-project, after the lovely person who inspired all of us in this endeavor and who we all miss.

None of all this would have been possible without the commitment of our researchers. In 2018, we welcomed two new junior group leaders, Patricia Pérez-Galán as head of the group Microenvironment in lymphoma pathogenesis and therapy and Virginia Amador as head of the group Functional characterization of oncogenic mechanisms in lymphomagenesis. Our Junior Group Leader Iñaki Martín-Subero was also awarded an ICREA professor position. We should all be proud of the recognition of Dr Àlvar Agustí as the 2018 Clinical Biomedical Research awardee of the Lilly Foundation and of the inclusion of 13 of our researchers among the 1% most cited investigators according to Clarivate Analytics.

IDIBAPS is firmly committed to promoting the education of the young scientific community. In 2018, 96 students defended their theses. We have organized 41 institutional seminars and a special mention goes to our Stepping-Stone training program, which seeks to provide young researchers at IDIBAPS with the non-scientific tools and skills that are key to the development of their careers. One of the major difficulties we have continued to face in 2018 is limited institutional funding for renewing and improving our support infrastructure. Nevertheless, IDIBAPS core facilities are making a tremendous effort to help our scientists reach their objectives. The activity of our five core facilities has increased significantly, providing almost 600 services. In 2018, the Biobank, the KTT and the Clinical Trials Unit, were recognized by the ISCIII as key participants in the respective national networks, Red Nacional de Biobancos, ITEMAS and SCREN. Of particular importance was the grant obtained from the Spanish Ministry of Science, Innovation and Universities to renew our informatics infrastructure. This support will allow us to meet the needs of our groups and expand the power of the many projects developed in our institution on the generation and analysis of biomedical big data.

Science needs to reach and permeate our society. We have developed new initiatives to reinforce our commitment in this regard. In 2018, we organized 48 activities that reached 2,131 people of all ages, from 4 years old in the Science Summer Camps and programs for young students who want to follow a scientific career, to the most elderly attending the talks at the Urgell Civic Center. It is notable that some of these activities received competitive funding from Barcelona City Council. We also began construction of the new website, which will improve the visibility of our researchers and of the institution. This new website will be linked to the new website of Hospital Clínic de Barcelona and the Portal Clínic, to reinforce collaboration between the two institutions.

We are well prepared to face the challenges that 2019 will bring us. Of particular importance is the continuing implementation of our Strategic Plan in a context of social change and economical constraint that, conditions that, we must acknowledge, are jeopardizing the high levels of scientific achievement not only of IDIBAPS but of the entire scientific community in our country. Our commitment as an institution and as individual researchers is unquestionably pushing science forward. Our greatest reward is to experience for ourselves how this work improves the life of our patients. IDIBAPS will continue to be an excellent benchmark center in this endeavor.

Elías Campo

Director

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About IDIBAPS

Additionally, 3 transversal groups perform research in Primary Care, Nursing, Pharmacology and Clinical Trials.

The Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) is a biomedical research institute of excellence. It combines clinical and basic research in order to accelerate the translation of the knowledge to the benefit of the patients. IDIBAPS is a CERCA (Research Centers of Catalonia) center and was first accredited as Instituto de Investigación Sanitaria (Instituto de Salud Carlos III) in 2009.

Scientific breakthroughs are never the result of chance. They are the fruit of long-term commitments that involve not only researchers, but also society as a whole.

IDIBAPS is a consortium that has made such a commitment, to encourage translational research, innovation and technological progress in the field of biomedicine, through different programmes addressing diseases with a high prevalence, morbidity and mortality in our society.
Founded in 1996, it is a public consortium formed by the Generalitat de Catalunya, Hospital Clínic de Barcelona, School of Medicine and Health Sciences of the University of Barcelona and, as an associated partner, the CSIC’s Barcelona Biomedical Research Institute.
The data presented in this Annual Scientific Report details the ever-growing scientific achievements made by IDIBAPS investigators and their capacity for attracting public and private funding. This enormous potential for capturing resources and their translation into applied results for clinical practice constitute the best guarantee for securing the future of the Institute and its impact on society and industry.
The Fundació Clínic per a la Recerca Biomèdica (FCRB) is a key institution to understand the functioning of IDIBAPS as a whole. It is a research foundation that provides researchers with administrative and management support. The IDIBAPS research community is composed of more than 1,500 people, grouped into 107 groups organized across 5 different areas of knowledge.

AREA 1

Biological aggression and response mechanisms

AREA 2

Respiratory, cardiovascular and renal pathobiology and bioengineering

AREA 3

Liver, digestive system and metabolism

AREA 4

Clinical and experimental neuroscience

AREA 5

Oncology and haematology

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FOREWORD IDIBAPS

Organisation chart

IDIBAPS requires a solid administrative infrastructure to support the state of the art research developed by its researchers.

IDIBAPS works together with the Fundació Clínic per a la Recerca Biomèdica (FCRB) to ensure efficiency and quality in the services offered to its research staff, in particular, in the areas of research project management and administration.

Marga Nadal, PhD

Director of Strategy

Elías Campo, MD PhD

Director of IDIBAPS and of FCRB

Rosa Vilavella

General Manager

Arantxa Fernández

Secretary

Gemma Pedrola

Secretary

Laura Lopera

Secretary [email protected] T.+34 93 227 18 30 CEK, mezzanine floor [email protected] T. +34 93 312 94 11 CEK, mezzanine floor [email protected] T. +34 93 227 18 42 CEK, mezzanine floor

Gemma Llaverías

Head of the Scientific Coordination Office

Marta Fernández

Head of the Human Resources Office

Sònia Meléndez

Head of the Accounting and Finance Office

Elisenda Vendrell

Head of the KTT Office

Ernest Costa

Head of the TIC Office

Daniel Arbós

Head of the Communication Office

Juan Suero

Head of the Purchasing

Gemma Pascual

Head of the Institutional Actions Office and General Services Office

Sandra Piquer

Coordinator of IDIBAPS laboratories

Guillem Masdeu

Head of the Legal Office

Aina Rodríguez

Head of IDIBAPS core facilities and Biobank coordinator

RESEARCH MANAGEMENT OFFICE

Sandra Pérez

Head of the Pre-Award Office for National Grants

Juan Abolafia

Head of the Pre-Award Office for International Grants

Judit Martínez

Head of the Post-award Grants Office

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Governance and structure

Governance is exercised through the following boards and committees:

THE SCIENTIFIC ADVISORY BOARD

Jesús San Miguel

Hospital Clínico de Salamanca

THE BOARD OF GOVERNORS
External leading scientists chosen by the Board of Governors, compose this board to advise IDIBAPS on the different scientific issues affecting its activities. These leading scientists have in-depth knowledge of the Spanish, European and/or American R+D+I systems as they hold positions in prestigious research institutions.
Conformed by representatives of the different institutions of the consortium, supervises IDIBAPS actions, budget and results. Its mission is to take scientific decisions in consultation with the Scientific Advisory Board, and to evaluate the implementation of the strategic plan.

Francisco Sánchez-Madrid

Hospital La Princesa, Madrid

Eugenio Santos

Centro de Investigación del Cáncer (CIC), Salamanca

Antonio Vidal-Puig

School of Clinical Medicine, University of Cambridge, UK

CHAIRMAN

Joan Gómez Pallarés

CHAIRMAN

General Director, Direcció General de Recerca, Departament d’ Empresa i Coneixement. Generalitat de Catalunya

José María Mato

CIC bioGUNE, Bilbao

BOARD MEMBERS

THE STEERING COMMITTEE

VICE-CHAIRMAN

Jesús Ávila

Centro de Biología Molecular Severo Ochoa (CBM), Madrid

Josep Maria Campistol

General Manager, Hospital Clínic de Barcelona

Which is responsible for the supervision of the progress achieved by the five IDIBAPS research areas, the recruitment of new scientists within the framework of different research programmes, and the evaluation of IDIBAPS training

Fernando Arenzana-Seisdedos

Institut Pasteur, Shangai, China

BOARD MEMBERS

Albert Barberà

General Director, Direcció General de Recerca I Innovació en Salut, Departament de Salut, Generalitat de Catalunya

Amparo Cano

Instituto de Investigaciones Biomédicas "Alberto Sols", CSIC-UAM, Madrid

programmes.

CHAIRMAN

Elías Campo

Director

Domènec Espriu

Research Vice-Dean, Universitat de Barcelona

Francisco Fernández Avilés

Hospital Gregorio Marañón, Madrid

MEMBERS

Lluís Calvo

Institutional Coordinator, Consejo Superior de Investigaciones Científicas (CSIC) in Catalonia

Ramon Gomis

IDIBAPS, Barcelona

Neus Agell

Vice-Dean of School of Medicine and Health Sciences

Universitat de Barcelona

José López Barneo

Instituto de Biomedicina de Sevilla (IBiS)

Francesc Cardellach

Dean of the School of Medicine, Universitat de Barcelona

Cristina Fillat

Group Leader

Carlos López Otín

Universidad de Oviedo

Gene therapy and cancer

Elías Campo

Director, IDIBAPS

• Carlos Macaya
• Joan Carles García-Pagán

Hospital Clínico San Carlos, Madrid

Antoni Castells

Medical Director, Hospital Clínic de Barcelona
Research Deputy Director (HCB)

Óscar Marín

King's College London, UK

Josep Maria Llovet

Group Leader

Translational research in hepatic oncology

Roser Cortés

Director, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC)

Federico Mayor

Centro de Biología Molecular Severo Ochoa, Madrid

Anna Planas

Coordinator of the IDIBAPS Research Area 4

SECRETARY

Lluís Rovira

Director, CERCA

Pura Muñoz

ICREA, Universitat Pompeu Fabra

Rosa Vilavella

General Manager

Angel Pellicer

SECRETARY

NYU School of Medicine, New York, US

Marga Nadal

Strategy Director

Ciril Rozman

Hospital Clínic de Barcelona, Universitat de Barcelona

13

FOREWORD IDIBAPS

GUEST MEMBERS

THE INTERNAL ADVISORY COMMITTEE

The Clinical Research Ethics Committee (Comitè d’Ètica d’Investigació amb Medicaments - CEIm) of the HCB

[email protected]

Montserrat Batlle

Works Committee President

IDIBAPS researchers representing all research areas advise the IDIBAPS director to implement the strategic decisions taken by the Board of Governors.

Jaume Bosch

Researcher

Hepatic hemodynamics and portal hypertension

The Animal Experimentation Ethics Committee (Comitè d’Ètica d’Experimentació Animal - CEEA) of the UB

CHAIRMAN

Francesc Cardellach

Dean of the School of Medicine

Universitat de Barcelona

Elías Campo

Director

Biosafety Committee (CBS)

STEERING COMMITTEE REPRESENTATIVES

Josep Maria Llovet

Group Leader

[email protected]

Fàtima Crispi

Researcher

Fetal and perinatal medicine

Core Facilities Committees

[email protected]

Translational research in hepatic oncology

Roser Cortés

Director

Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC)

Joan Carles García-Pagán

Research Deputy Director

Hospital Clínic de Barcelona

Mentoring Committee Training Committee

[email protected]

INSTITUTIONAL REPRESENTATIVES

Joan Cid

Physicians’ Representatives

Hospital Clínic de Barcelona

Josep M. Gatell

National Coordinator of the RETIC on AIDS

Clinicians and Research Committee Ombuds Committee

Anna Novials Francesca Pons

Francesc Graus

Cellex building representative

Guadalupe Mengod

Deputy Director

Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC)

Marc Roda Joan Serratosa [email protected]

Anna Novials

Group Leader

Pathogenesis and prevention of diabetes