Raya Group

STEM CELL POTENCY

Reprogramming the potency of somatic cells to accelerate stem cell-based regeneration

We investigate the mechanisms by which some animal species can regenerate their hearts. This knowledge informs clinically translatable strategies to improve heart repair in patients
Angel Raya
Coordinator, Regenerative Medicine Program of IDIBELL
Director of P-CMRC
araya@idibell.cat

Lab focus

During embryo development, the potency of the zygote is deployed through coordinated and stereotypical changes in cell behaviors and processes of tissue patterning, ultimately resulting in the formation of an entire, highly complex organism in a relatively short period of time. Throughout this process, the developmental potency of individual cells, i.e. their ability to give rise to cells of a different type than their own, is progressively lost, so that somatic cells in adult individuals retain very limited potency (such as in rare adult stem cells) or show no potency at all.

Our laboratory is interested in understanding the mechanisms that govern the degree of potency of human somatic cells, and how it can be experimentally increased for conditions where doing so may be of biomedical relevance. Specifically, the context in which we investigate these issues is mainly centered on the paradigm of cardiac regeneration/repair. Overall, our research takes advantage of a variety of experimental paradigms (zebrafish heart regeneration, human iPSC generation and differentiation), approached from a multi-disciplinary perspective, ranging from bioengineering approaches to 3D stem cell differentiation to single-cell genetic lineage tracing analyses and genetic manipulation of human cells, aimed at tackling important current issues in biology and biomedicine, such as the mechanisms that control the establishment and maintenance of developmental potency, the initiation and progression of the regenerative process, and the differentiation and functional maturation of human cardiomyocytes, and the development of genuinely human models of human disease.

Why it matters

Heart-related diseases are the main cause of mortality in the world, with ischemic heart disease being the single most frequent condition accounting for the death toll. This results from the very limited ability of the mammalian heart to regenerate on its own, and underscores the pressing biomedical need to finding ways for potentiating this ability (heart regeneration) and/or providing new cardiac cells to replace the lost or damaged ones (heart repair).

Keywords

Heart regeneration, Induced reprogramming, Disease modeling, Cardiac tissue engineering, Stem cell differentiation

Publications

Saludas L, Garbayo E, Mazo M, Pelacho B, Abizanda G, Iglesias Garcia O, Raya A, Prosper F, Blanco-Prieto MJ. (2019) Long-term engraftment of human cardiomyocytes combined with biodegradable microparticles induces heart repair. J Pharmacol Exp Ther 370(3):761-771. Epub 2019, Feb 6.
Uroz M, Garcia-Puig A, Tekeli I, Elosegui-Artola A, Albertazzi L, Roca-Cusachs P, Raya A, Trepat X. (2019) Traction forces at the cytokinetic ring regulate cell division and polyploidy in the migrating zebrafish epicardium. Nat Mater 18(9):1015-1023. Epub 2019, Jun 3.
Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L. (2019) Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases. J Clin Invest 129(10):4539-4549. Epub 2019, Sep 16.
Benzoni P, Campostrini G, Landi S, Bertini V, Marchina E, Iascone M, Ahlberg G, Olesen MS, Crescini E, Mora C, Bisleri G, Muneretto C, Ronca R, Presta M, Poliani PL, Piovani G, Verardi R, Pasquale ED, Consiglio A, Raya A, Torre E, Lodrini AM, Milanesi R, Rocchetti M, Baruscotti M, DiFrancesco D, Memo M, Barbuti A, Dell’Era P. (2019) Human iPSC modeling of a familial form of atrial fibrillation reveals a gain of function of If and ICaL in patient-derived cardiomyocytes. Cardiovasc Res Epub 2019, Aug 28.
Castaño J, Aranda S, Bueno C, Calero-Nieto FJ, Mejia-Ramirez E, Mosquera JL, Blanco E, Wang X, Prieto C, Zabaleta L, Mereu E, Rovira M, Jiménez-Delgado S, Matson DR, Heyn H, Bresnick EH, Göttgens B, Di Croce L, Menendez P, Raya A and Giorgetti A. (2019) GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm. Stem Cell Rep 13(3):515-529. Epub 2019, Aug 8.
Members
Current Members
Léa Pourchet
Post Doc
Daniel Uribe
Post Doc
Yvonne Richaud
Senior Research Assistant
Jorge Castillo
Post Doc
Jagoda Litowczenko-Cybulska
Post Doc
Cristina García
Research Assistant
Karine Tadevosyan
PhD student
Demetria Kyriacou
PhD student
Laura Casado
PhD student
Yannis Lazis
PhD student
Alba Morillas
Research Assistant
Lorenzo Masseroni
ERASMUS Master student
Luca Ruvo
Erasmus Master student
Maria van Dongen
Assistant to Director
Gaia Galluzzi
Erasmus Master student
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Angel Raya
ICREA Research Professor Coordinator, Regenerative Medicine Program of IDIBELL
Director of P-CMRC

araya@idibell.cat

Prof. Angel Raya holds an MD and a PhD from the University of Valencia. He pursued postdoctoral training at the Instituto de Investigaciones Citológicas (currently, Centro de Investigación Príncipe Felipe) in Valencia, from 1995 to 2000. He then was a Research Associate (2000-2004) and a Senior Research Associate (2004-2006) at the Gene Expression Laboratory of the Salk Institute for Biological Studies, La Jolla, CA (USA).

He returned to Spain in 2006 as an ICREA Research Professor. He was CMRB´s Scientific Coordinator until 2009, when he joined the Institute for Bioengineering of Catalonia (IBEC) as group leader of the Control of Stem Cell Potency Group. In 2014 he was appointed Director at CMRB.

Research in Prof. Raya’s group aims to understand the tissue, cellular and molecular mechanisms that determine the regenerative response in certain species of vertebrates, as well as the genetic and epigenetic mechanisms that control cellular reprogramming. This phenomenon provides a link between the traditional study of epimorphic regeneration and the induced pluripotency strategies of regenerative medicine.

Léa Pourchet
Post Doc
lpourchet@idibell.cat

Dr. Léa Pourchet obtained a double degree in 2012 as engineer with a research Master speciality in innovative materials at ITECH (Institut Textile Et Chimique) and Ecole Centrale de Lyon, in France. She started to work as research engineering at ICBMS (Institut de Chimie et de Biochimie Moléculaire et Supramoléculaire) for polymer development applied to 3D printing. She also participated in the 3D.FAB plateform creation specialized in 3D printing for healthcare.

Between 2015 and 2018, she performed her doctorate in the biotechnological field, under the supervision of Dr. Christophe Marquette at the same laboratory. Her studies was focus on the bioink development for 3D bioprinting with formulation studies and tissue characterization. This work was achieved in a collaborative environment and oriented at three problematics: skin 3D bioprinting with the dermis and its maturation towards a total skin, cartilage 3D bioprinting with mesenchymal stem cells bioprinted and the vascularization incorporation thanks to the use of endothelial cells and a perfusable tissue with a dynamic culture approach in a bioreactor.

Dr. Léa Pourchet joined the Center of Regenerative Medicine in Barcelona CMR[B] in September 2019 as a postdoctoral researcher at Dr. Angel Raya lab focusing in the complex cardiac tissue engineering thanks to 3D bioprinting using iPSCs.

Daniel Uribe
Post Doc
duribe@idibell.cat

Daniel Uribe received his bachelor’s degree in Biochemistry from in the Austral University of Chile (UACH) in 2015. During this time, Daniel studied the effect of hypoxia on the expression and activity of drug resistance transporters of the ATP-binding cassette family in glioblastoma cells.

In 2020, Daniel obtained his PhD degree from in the UACH, where he studied the role of adenosine signaling on the regulation of stemness in Glioblastoma Stem-like Cells (GSCs) under hypoxic conditions. In addition, he characterized Proneural and Mesenchymal subtypes of GSCs obtained from patients, and evaluated the activation status of adenosine signaling in both subpopulations.

In parallel, Daniel worked on a project related to the clinical monitoring of gallbladder cancer (GBC) in collaboration with the Valdivia Hospital and the Institute of Immunology and Immunotherapy of the University of Chile. In this project, Daniel analyzed the presence of chemoresistance markers in GBC for the preparation of clinical software with prognostic and predictive potential.

In February 2022, Daniel joined Dr. Ángel Raya’s group as a postdoctoral researcher under the Marie Skłodowska-Curie action, focusing on studying hypoxia as a method to promote cardiac regeneration. As part of his objectives, Daniel studies the effects of hypoxia on energy metabolism and extracellular matrix composition in iPSC-derived cardiomyocytes and in zebrafish cardiac regeneration models.

Yvonne Richaud
Senior Research Assistant
irichaud@idibell.cat

Yvonne Richaud obtained her BSc. in Biochemistry by the Universidad Veracruzana (Mexico) in 1990. Since 1991 to 2007 she worked as a research staff member at the Laboratory of Immunology and Rheumatology from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirán (Mexico City). Under the direction of Drs. D. Alarcón Segovia and L. Llorente, she participated in several projects focused on the study of cytokines and B-cell hyperactivity of rheumatic autoimmune diseases, particularly systemic lupus erythematosus. Important collaborations of her work have been performed with the research group of Professors D. Emilie and P. Galanaud (INSERM-U131, Clamart, France).

In 2007, Yvonne came to Barcelona and joined the CMR[B] as a research technician under the direction of Dr. Ángel Raya, particularly in the field of cell reprograming.

Then, from 2009 to 2015, she has been working at the Institute for Bioengineering of Catalonia (IBEC) in Dr. Raya’s research group Control of Stem Cell Potency as a senior technician participating in several projects of disease modelling through induced pluripotent stem cells (iPSC).

On January 2016, she came back to the CMR[B] and, since then, she has carried on her work in cell reprogramming and disease modelling.

Jorge Castillo
Post Doc
jcastillo@idibell.cat

Jorge Castillo received his bachelor degree in biological sciences at National Autonomous University of Mexico (UNAM) in 2008. During this time he studied the hormonal bases that regulate the onset of paternal behavior in rodents.

From 2008 to 2012 Jorge studied his master’s degree in Biochemical Sciences at the Institute of Cellular Physiology (UNAM) where he worked with the molecular bases that regulate the storage and silencing of maternal RNAs during the formation and inheritance of the germ line, using zebrafish as a model study organism.

Then, in 2018 Jorge obtained his Ph.D. in Biomedical Sciences at the Biotechnology Institute (UNAM). In his doctoral thesis he focused on studying the molecular mechanisms that regulate the heart development, specifically he found, using CRISPR-Cas9 system, that the SWI/SNF chromatin-remodeling complex subunit BAF57, plays an essential role during the zebrafish heart development. During this period Jorge gained solid experience about the study of the heart development and the epigenetic mechanisms involved in this process.

In November 2019 Dr. Castillo joined Dr. Angel Raya’s group as a postdoctoral researcher, focusing on studying the role of the extracellular matrix during the cardiac regeneration processes in zebrafish.

Jagoda Litowczenko-Cybulska
Post Doc
jlitowczenko@idibell.cat

Dr. Jagoda Litowczenko-Cybulska received her PhD in Biological Sciences in 2020 from the Adam Mickiewicz University in Poznan, Poland, for studies on biomedical applications of nanotechnology carried out at the Faculty of Biology and at the NanoBioMedical Center (NBMC). Results obtained during her PhD studies allowed Dr. Litowczenko-Cybulska to receive her first grant related to study of polymeric/carbon nanostructures scaffolds with specific surface topography for neural stem cells growth and differentiation in 2017. After her PhD defence, she joined NBCM firstly as a Research Associate, Senior Specialist and finally as an Assistant Professor working in the interdisciplinary field of materials engineering, where she obtained two more scientific grants focusing on the development of polymeric tubular scaffolds by 3D printing technology in order to increase the regeneration of peripheral nerves after injuries. In 2022, Dr. Jagoda Litowczenko-Cybulska was awarded the prestigious START prize from the Foundation for Polish Science, for the most talented young researchers in Poland.

In September 2022, Jagoda joined Dr. Ángel Raya’s group as a postdoctoral researcher under the Marie Skłodowska-Curie Individual Fellowship (MSCA-IF), where she works on the development of cell-laden 3D printed vascular grafts which will contribute to the understanding of the subject of vascular tissue engineering.

Cristina García
Research Assistant
cgarcía@idibell.cat

Cristina García studied a Higher Technical Certificate in Clinical Diagnosis laboratory techniques at the Roger de Llúria IFP between 2010 and 2012. During her studies she did an internship at the units of microbiology, blood bank & emergencies at the Moisès Broggi Hospital, as well as at the Control of Stem Cell Potency lab at the Institute for Bioengineering of Catalonia (IBEC), under the supervision of Dr. Ángel Raya.

Once she obtained her B category diploma on Laboratory Animal Research, she started working as a technician responsible of zebrafish facilities maintenance and she was also carrying out the generation and care of transgenic lines. Cristina also played the role of assistant in molecular biology at the laboratory of Dr. Ángel Raya, where she had been doing her internship some time before. During this period, she acquired a great experience in both zebrafish care and laboratory techniques.

In 2015 she moved to the CMR[B] doing the same functions than before, also with the Ángel Raya’s team. In 2016 she has attended a course on the genetic basis of complex diseases at Aetel, thus increasing her knowledge in this field.

Karine Tadevosyan
PhD Student
ktadevosyan@idibell.cat

Karine Tadevosyan obtained her specialist degree (2007-2013) in medical biochemistry at the Department of Medical Biochemistry and Biotechnology of Russian-Armenian (Slavonic) University, Yerevan, Republic of Armenia.

In 2010-2012 she worked as an assistant at the Laboratory of Biochemistry and Immunopathology of the Center of Medical Genetics and Primary Health Care, Yerevan, Republic of Armenia. Karine was involved in the project related to investigation of immunohistochemical and genetic approaches in the diagnosis of breast cancer. The main purpose was the identification of the most relevant technics for diagnostics of Her2/neu receptor status among FISH (Fluorescent in situ hybridization), CISH (Chromogenic in situ hybridization) and immunohistochemistry, for appropriate hormone therapy.

In 2012-2017 Karine worked as a junior researcher at the Laboratory of Human Genomics and Immunomics of National Academy of Sciences of Republic of Armenia. Under supervision of Dr. Elina Arakelova and Dr. Anna Boyajyan she performed her diploma thesis (2012-2013) related to the impact of amino acids of Shiff basis on the adaptogenic properties of the organism in ionizing radiation. The study was focused on investigation of the influence of L-histidine-isonicotinilaldehyde and Cu-L-histidineisonicotinilaldehyde on molecular-level changes in the immune and antioxidant systems of the animal organism in the conditions of ionized radiation.

In 2013-2017 Karine studied the genetic mutations of JNK/AP-1 signaling pathway in ischemic stroke. The main goal of project was the evaluation of the association of functional-genetic variants of the members of JNK/AP-1 signaling pathway with the risk of IS.

In 2016-2017 Karine worked as a physician-virologist at the Virology Laboratory of National Center of Diseases Control and Prevention, Ministry of Health, Yerevan, Republic of Armenia. During this period, she participated in workshops focused on the virus isolation procedures (maintenance of cell cultures and harvesting of isolates), biorisk management and international shipping of infectious substances.

In June 2017 Karine joined the Center of Regenerative Medicine in Barcelona (CMRB) as a laboratory technician, focusing on the generation of human iPS-derived cardiac tissues for regenerative medicine purposes.

Demetria Kyriacou
PhD student
dkyriacou@idibell.cat

Demetria Kyriacou obtained her undergraduate degree in Biology from the University of Nottingham, UK in July 2020. After that, she continued her studies and obtained her Master’s degree in Prenatal Genetics and Fetal Medicine from University College London (UCL) in October 2021. For her MSc thesis, she focused on the role of mesenchymal to epithelial transition pathway during chemical reprogramming of human amniotic fluid stem cells (hAFSCs) to pluripotent stem cells, under the supervision of Dr. Pascale V Guillot.

Currently, Demetria is working on her PhD project focused on characterizing the early events driving carcinogenesis in Constitutional Mismatch Repair Deficiency (CMMRD) syndrome using iPSC-neural progenitors under the direction of Dr. Ángel Raya and Dr. Marta Pineda.

Laura Casado
PhD student
lcasadom@idibell.cat

Laura Casado obtained her bachelor’s degree in Biomedical Sciences from the Universitat Autònoma de Barcelona in 2017. After finishing, she spent three months working as an intern, thanks to the grant Oportunidad al Talento (ONCE), in the “Cellular plasticity and disease” research group at the Institute for Research in Biomedicine (IRB) Barcelona.

In 2018, she finished her Master’s degree in Regenerative Biomedicine from the University of Granada. Her research was focused on the study of the expression of androgen receptor splice variants 7 and 9 during the development of prostate cancer resistances in the “Gene regulation, Stem cells and Development” research group at the Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO).

Currently, Laura is working on her PhD Project focused on cardiac tissue engineering using 3D bioprinting under the direction of Dr. Ángel Raya at the Regenerative Medicine Program of IDIBELL.

Yannis Lazis
PhD Student
ilazis@idibell.cat

Yannis Lazis obtained his Integrated Master’s degree (2019) in Biological Applications & Technology from the University of Ioannina, Greece. The core of his studies was directed into Biomolecular Sciences & Biotechnology and during this time, he joined Dr. Kouklis lab at the Institute of Molecular Biology & Biotechnology as an intern, obtaining experience on the differentiation of mESCs into mesoendodermal fate, as well as, on the characterization of VE-cadherin antibodies in different tissues.

He joined the Center of Regenerative Medicine in Barcelona (CMR[B]) in 2018 to work on his Master thesis. His research was focused on the modeling of hypertrophic cardiomyopathy using the iPS technology and the CRISPR/Cas9 system.

Currently, Yannis is working on his PhD project focused on the heart regeneration process using zebrafish as an animal model, under the direction of Dr. Ángel Raya.

Alba Morillas
Research Assistant
amorillas@idibell.cat

Alba Morillas studied a Higher Technical Certificate in Clinical Diagnosis laboratory techniques at the Miquel Martí i Pol IES between 2013 and 2015. During her studies she did an internship at the units of Biochemistry and Immunology at the Bellvige Universitary Hospital.

Once completed the specialization, she worked at the Bellvige Universitary Hospital in departments of Special Biochemistry Hormones and Molecular Biology. During this period, she acquired a great experience in the techniques applied in molecular biology.

Since February 2018, she is a Specialist Technician of the Molecular Biology Platform at CMRB. She carries out technical supporting tasks for the researchers of the center, collaborating in different projects and research lines.

Lorenzo Masseroni
ERASMUS Master student
lmasseroni@idibell.cat

Lorenzo Masseroni obtained his Bachelor’s degree in Medical Biotechnology, at the University of Milan in 2019. He carried out his Bachelor thesis in Prof. Landsberger’s lab at the University of San Raffaele, analysing anatomic and functional anomalies that characterize CDKL5 mouse model through magnetic resonance imaging. In 2020, he enrolled in his Master’s degree in Biology applied to medical research at the University of Milan.

Lorenzo joined Dr. Ángel Raya’s group in October 2021 under the framework of Erasmus+. The main research interest of his master thesis is focused on understanding the role of RNA-Methyl transferase Mettl3 in apoptosis in human iPS cells. At the same time he is involved in projects related to zebrafish heart regeneration.

Luca Ruvo
ERASMUS Master student
lruvo@idibell.cat

Luca Ruvo obtained his Bachelor’s degree in Cellular and Molecular Biotechnology, at the University of Teramo in 2019. After an Erasmus+ project in Andalucía where he spent a semester studying in the University of Granada, he carried out his Bachelor thesis in the modulation of inflammatory processes through the intestinal microbiota attending the internship in the Microbiology Laboratory of the University of Teramo. He enrolled in his Master’s degree in Molecular and Cellular Biology at the University of Bologna.

He joined Dr. Ángel Raya’s group in March 2022 winning an Erasmus+ traineeship grant for one year. His Master’s thesis project focuses on the maintenance and differentiation of iPSCs for the development of biomimetic platforms for drug discovery (Heart-on-a-chip).

Gaia Galluzzi
ERASMUS Master student
ggalluzzi@idibell.cat

Galluzzi obtained her Bachelor’s degree in Biology Sciences at Università degli Studi di Milano in 2019 and mastered in Genetics and Molecular Biology in 2021 at La Sapienza Università di Roma. From 2020 to 2021 she worked on her master thesis project at Mendel Institute in Rome focusing on cell reprogramming of several iPSC lines and on the molecular characterization of an inheritant Parkison’s mutation under the supervision of Dr. Jessica Rosati.

She joined Raya’s group as a postgraduated trainee with the Erasmus+ programme and she is currently working on cardiac regeneration through 3D bioprinting using iPSCs’ derived cardiomyocytes with Léa Pourchet.

Undergraduate students
Marta Lorente
Marta Miret
Mario Barilani
Marta Farres Mendez
Isil Tekeli
Bahaa Arefai
Anna Garcia-Puig
Rubén Escibá
Cybil Nelson
Sara Tamagno
Patricia Marques
Isabel Ramos
Laia Gregori
Ioannis Papadopoulos
Queralt Anglada
Dalel Saidi
Arnau Biosca
Carola Fernandez
Qi Zhu
Jonathan De Smedt
Sebasthian Santiago
Alessia Urzi
Leonard Gable
Elisa Hahn
Ipek Aktan
Eunyeong Kim
Omur Besbinar
Iannis Lazis
Gaia Galluzzi
Graduate students
Eduard Sleep
Ignasi Rodriguez-Piza
Adriana Sanchez-Danes
Alba Mateos
Annarita Oranger
Marcel Orpí
Isaac Canals
Emanuelle Celauro
Clara Sanjurjo
Isil Tekeli
Claudia di Guglielmo
Juan Crespo Santiago
Juan Luis Vázquez
Marcel Orpí
Sabrina Turturro
Maria Valls-Margarit
Carles Calatayud
Zoe Boyer
Anna Garcia-Puig
Rubén Escribá
Postdoctoral Researchers
Núria Montserrat
Sergio Mora-Castilla
Vlad Pekarik
Alexandre da Cruz
Adriana Rodríguez-Marí
Marianna Vitaloni
Ruben Peco
America Martinez Calleja
Julian Pulecio
Sylvia Bedford
Samuel Ojosnegros
Ina Berniakovich
Anna Seriola
Mario Notari
Meritxell Rovira
Fernando Gutiérrez
Cristina Prat
Research assistants
Alberto Garcia Martinez
Lluis Martorell
Senda Jimenez
Karine Tadevosyan