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
Headshot of Angel Raya
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
Headshot of Virginia Nieto
Virginia Nieto
Post Doc
Headshot of Daniel Uribe
Daniel Uribe
Post Doc
Headshot of Yvonne Richaud
Yvonne Richaud
Senior Research Assistant
Headshot of Jorge Castillo
Jorge Castillo
Post Doc
Headshot of Taqwa Qasem
Taqwa Qasem
PhD student
Headshot of Cristina García
Cristina García
Research Assistant
Arnau Boix
Post Doc
Headshot of Yuan Yang
Yuan Yang
PhD student
Headshot of Laura Casado
Laura Casado
PhD student
Headshot of Edgar Lorenzo
Edgar Lorenzo
Research Technician
Headshot of Alba Morillas
Alba Morillas
Research Assistant
Headshot of Senda Jiménez-Delgado
Senda Jiménez-Delgado
Staff scientist
Headshot of Karine Tadevosyan
Karine Tadevosyan
Visiting Scientist
Headshot of Maria van Dongen
Maria van Dongen
Assistant to Director

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.

Headshot of Virginia Nieto
Virginia Nieto
Post Doc
Virginia Nieto Romero obtained a BSc degree in Biotechnology from University of León in 2013, a MSc degree from Complutense University of Madrid in 2014, and a PhD degree from Autonomous University of Madrid in 2021, for work done at the Cell Technology Division, Biomedical Innovation Unit (CIEMAT-CIBERER-IIS/FJD, Madrid, Spain), under the supervision of Drs. María García-Bravo and José Carlos Segovia. During her PhD studies, Virginia developed different gene editing strategies in combination with a protocol for direct reprogramming toward hepatic cells to generate locus-specific gene corrected induced-hepatocytes from patient fibroblasts as an alternative cell source for liver cell replacement therapy for the treatment of Primary Hyperoxaluria type1 (PH1), a rare inheritance liver disorder.
Dr. Virginia Nieto-Romero joined Ángel Raya’s laboratory in IDIBELL in October 2023 as a postdoctoral researcher working on skeletal muscle differentiation of pluripotent stem cells.

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.

Headshot of Taqwa Qasem
Taqwa Qasem
PhD Student
Taqwa Qasem obtained her Bachelor’s degree (2017) in Medical Laboratory Sciences from Jordan University of Science and Technology (JUST), Jordan, carrying out undergraduate studies on the medical diagnosis of vampire disease. She pursued a Master’s degree in Chemistry at Eastern Mediterranean University (EMU), North Cyprus-Turkey from 2018-2020 studying the application of bio-polymers in medical research, in particular the impact of Alginate-Gelatin Ratios and Lithium on SK-Hep1 Cell Proliferation Encapsulated in Bio-Polymeric Microspheres.
Taqwa worked from 2020-2022 as Research Assistant in the Faculty of Medicine at Yarmouk University, Jordan, being involved in COVID-19 research.
In March 2024, Taqwa joined Angel Raya’s group at IDIBELL to carry out her PhD on the topic ‘Modeling hypertrophic cardiomyopathy using iPSC-based advanced culture systems’.

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.

Arnau Boix
Post Doc
Dr. Arnau Boix received his bachelor’s degree in biotechnology from the Autonomous University of Barcelona (UAB) in 2016, where he undertook an internship at the Centre for Animal Biotechnology and Gene Therapy (CBATEG). He followed his studies obtaining a master’s degree in advanced biotechnology at the UAB School of Engineering in 2017, specializing in industrial biotechnology.
In 2022 Arnau obtained his PhD in Biotechnology at the UAB School of Engineering, conducting his thesis at the Cellular and Bioprocess Engineering Research Group (GECIB) under the direction of Prof. Dr. Francesc Gòdia. He demonstrated that the Spike protein from SARS-CoV-2 can be incorporated to Gag-VLPs, with the aim to generate potential vaccine candidates. His doctoral thesis focused on the production, purification and characterization of these particles, while evaluating the effect that different Spike mutations have on VLP functionalization and immunogenic potential. In parallel, Arnau generated and characterized different stable cell lines to produce Gag-VLPs, using random integration and CRISPR-Cas9 technology as well as optimizing the production bioprocess. In 2018 he performed an international doctor research stay at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, where he developed a RMCE-competent stable cell line by means of lentiviral transduction. From 2018 to 2021 Arnau also served as a lecturer at UAB.
In September 2023 Dr. Boix joined Dr. Ángel Raya’s group at P-CMR[C] as a postdoctoral researcher, focusing on cell culture scale up and bioprocess operations.

Yuan Yang
PhD student
yuyang@idibell.cat

Yuan Yang completed her master’s degree in basic medicine at the School of Basic Medicine, China Three Gorges University in Hubei, China, from 2018 to 2021. Throughout her master’s studies, she dedicated her research to investigating the mechanisms behind the male reproductive toxicity induced by two common environmental pollutants, Perfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS). Notably, she made a significant discovery during her research, highlighting the efficacy of icariin, a flavonoid derived from Epimedium, a Traditional Chinese medicine, in reducing PFOS-induced testicular toxicity.

Following the completion of her master’s degree, Yuan worked as a research assistant between 2021 and 2022 in Dr. Joe Z Zhang’s group at the Shenzhen Bay Laboratory in Shenzhen, China. During her time there, she actively participated in workshops that focused on utilizing the CRISPR/Cas9 technique to generate genome-edited hiPSC (human induced pluripotent stem cell) lines. The aim of these workshops was to elucidate the underlying mechanisms of fibrosis in hypertrophic cardiomyopathy (HCM).

In May 2023, Yuan Yang began her journey as a joint Ph.D. student in the joint Ph.D. program of the Shenzhen Bay Laboratory (SZBL) and The Institute of Biomedical Research of Bellvitge (IDIBELL), at the Program for Clinical Translation of Regenerative Medicine in Catalonia (P-CMR[C]), under the guidance and supervision of two esteemed researchers, Dr. Ángel Raya and Dr. Joe Z Zhang.

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.

Headshot of Edgar Lorenzo
Edgar Lorenzo
Research Technician
Edgar Lorenzo obtained his Bachelor’s degree in Biomedical Engineering from the Universitat de Girona in June 2023. He conducted his Bachelor’s thesis on skeletal muscle tissue engineering using 3D bioprinting at P-CMR[C], while also pursuing an internship to establish a primary skeletal muscle cell culture.
In July 2023, he joined P-CMR[C] as a Research Technician in Dr. Angel Raya’s group to continue his work on muscle cells isolation, expansion and differentiation.

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.

Headshot of Senda Jiménez-Delgado
Senda Jiménez-Delgado
Staff scientist
Senda Jiménez-Delgado obtained her PhD degree in Biology from the Universitat de Barcelona in 2008, for her work on the Evo-Devo field, studying somitogenesis during the embryonic development of the cephalochordate amphioxus.
She joined the CRM[B] in 2009 as a research assistant Dr. Ángel Raya’s group. Until 2018, she was involved in a variety of projects related to cell reprogramming and cardiomyocytes differentiation, as well as in the study of heart regeneration in the zebrafish.
From 2018 to 2023, she was worked in Verena Ruprecht’s group at CRG as a lab manager and setting up molecular techniques such as CRISPR/Cas9 and CRISPR/Cas13 to generate KO, KI and KD in zebrafish to study different molecular processes related with mechanobiology during early embryogenesis.
In September 2023, she joined P-CMR[C] program as a Staff Scientist in Ángel Raya’s group, where she is a lab manager and senior specialist in molecular biology and zebrafish research.

Karine Tadevosyan
Visiting Scientist
ktadevosyan@idibell.cat

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

From 2010 to 2012, she worked as an assistant at the Laboratory of Biochemistry and Immunopathology at the Center of Medical Genetics and Primary Health Care in Yerevan. From 2012 to 2017, Karine was a junior researcher at the Laboratory of Human Genomics and Immunomics at the National Academy of Sciences of Armenia. Under the supervision of Dr. Elina Arakelova and Dr. Anna Boyajyan, she conducted her diploma thesis (2012-2013), studying the impact of Schiff base amino acids on adaptogenic properties in response to ionizing radiation. From 2013 to 2017, she focused on researching genetic mutations in the JNK/AP-1 signaling pathway related to ischemic stroke.

In 2016-2017, Karine worked as a physician-virologist at the Virology Laboratory of the National Center for Disease Control and Prevention, Ministry of Health, Yerevan, Armenia.

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

From 2020 to 2024, Karine pursued her PhD under the supervision of Dr. Angel Raya, concentrating on developing a heart-on-a-chip platform for cardiac physiology and drug toxicity testing.

In September 2024, Karine joined the Biomedical Applications Group at the National Center of Microelectronics (CSIC) in Barcelona as a postdoctoral researcher. She is currently advancing the heart-on-a-chip platform as part of the HETERCHIP project. Karine is also a visiting scientist in Dr. Raya’s group, collaborating on the validation of the heart-on-a-chip platform using iPSC-derived cells.

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
Lorenzo Masseroni
Luca Ruvo
Yanlin Yang
Yuliya Yuryeva
Josep Maria Jordà
Marianna Paladini
Yannick Richter
Aurora Ferrari
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
Demetria Kyriacou
Xuan Li
Karine Tadevosyan
Yannis Lazis
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
Léa Pourchet
Jagoda Litowczenko-Cybulska
Fernanda Fredericksen
Research assistants
Alberto Garcia Martinez
Lluis Martorell
Senda Jimenez