The Moretti group uses pluripotent stem cell derived cardiac organoids to study mechanisms of human heart diseases and dissect principles of human cardiac development for the design of novel therapeutic strategies for heart repair and regeneration.
Our laboratory is interested in the development of the human heart and the mechanisms of cardiac diseases and regeneration, with the ultimate aim to develop innovative therapies for patients with cardiovascular disorders. To address this, we harness the potential of human pluripotent stem cells to differentiate into various cardiac cell types in vitro and have developed advanced 2D and 3D culture systems that we combine with cutting-edge technologies such as single-cell RNA sequencing, CRISPR/Cas9 gene editing, bioprinting, and sophisticated imaging techniques.
By using induced pluripotent stem cells (iPSCs) from disease patients, we have pioneered the modeling of inherited cardiac diseases in 2D muscle cells and demonstrated their unique value for informing drug design and diagnostics in a personalized fashion.
Recently, we have succeeded in generating the first heart organoid from human pluripotent stem cells showing the co-development of ventricular myocardium and epicardium, which we named epicardioid. The epicardium - the outer layer of the heart - plays key roles during cardiac development and regeneration, acting as the source of multiple cell types and important signalling factors. Epicardioids recapitulate the cellular complexity, organization, and function of the heart at high degree. We therefore plan to use them to address open questions in human heart morphogenesis, investigate more complex heart diseases like congenital malformations, and discover new paths for human epicardium-mediated heart repair. Moreover, we aim at optimizing the epicardioid model to mirror the cellular makeup and architecture of the heart with even superior fidelity.
The Moretti lab has strong collaborations with research groups at Klinikum rechts der Isar der TUM, German Heart Center Munich, TUM Center for Functional Protein Assemblies, TUM Institute for Biomedical Engineering, Helmholtz Munich, LMU and Yale University. The main lab location is at the Klinikum rechts der Isar der TUM, Department of Internal Medicine I, Regenerative medicine of Cardiovascular Diseases.
- Prof. Dr. Alessandra Moretti
Chair of Regenerative Medicine of Cardiovascular Diseases, group leader - Dr. Christiane Schmautz
Scientific coordinator - Dr. Tatjana Dorn
Senior scientist (developmental biology, lineage decision) - Dr. Monika Nowak-Imialek
Veterinarian scientist (porcine expanded pluripotent stem cells & human-pig chimeras) - Dr. Alexander Göedel
Physician scientist (bioinformatic data analysis) - Dr. Christine Poch
Physician scientist (3D tissue engineering & functional imaging) - Sophie Zengerle
PhD student (organoids and modeling of congenital heart disease) - Sinem Sürmeli
PhD student (CRISPR-based genome editing) - Luis Felipe Monge Mora
PhD student (cardiac organiods and injury models) - Tobias Ellinger
PhD student (cardiac organiods and imaging) - Eleonore Baier
MD student (3D tissue engineering and disease modeling) - Marco Crovella
Technician (animals and histology) - Christina Scherb
Technician (molecular biology) - Birgit Campbell
Technician (cell culture and iPSC generation)
Epicardioid single-cell genomics uncover principles of human epicardium biology in heart development and disease. Meier AB, Zawada D, De Angelis MT, Martens LD, Santamaria G, Zengerle S, Nowak-Imialek M, Kornherr J, Zhang F, Tian Q, Wolf CM, Kupatt C, Sahara M, Lipp P, Theis FJ, Gagneur J, Goedel A, Laugwitz KL, Dorn T, Moretti A. Nature Biotechnology (2023)
Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools. Zawada D*, Kornherr J*, Meier AB*, Santamaria G*, Dorn T, Nowak-Imialek M, Ortmann D, Zhang F, Lachmann M, Dreßen M, Ortiz M, Mascetti VL, Harmer SC, Nobles M, Tinker A, De Angelis MT, Pedersen RA, Grote P, Laugwitz KL§, Moretti A§, Goedel A§. Nature Communications (2023) *equal contribution, §corresponding authors
Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors. Poch CM*, Foo KS*, De Angelis MT*, Jennbacken K*, Santamaria G*, Bähr A*, Wang QD, Reiter F, Hornaschewitz N, Zawada D, Bozoglu T, My I, Meier A, Dorn T, Hege S, Lehtinen ML, Long Tsoi Y, Hovdal D, Hyllner J, Schwarz S, Sudhop S, Jurisch V, Sini M, Fellows MD, Cummings M, Clarke J, Baptista R, Eroglu E, Wolf E, Klymiuk N, Lu K, Tomasi R, Dendorfer A, Gaspari M, Parrotta E, Cuda G, Krane M, Sinnecker D, Hoppmann P, Kupatt C§, Fritsche-Danielson R§, Moretti A§, Chien KR§, Laugwitz KL§. Nature Cell Biology (2022) *equal contribution, §corresponding authors
Sequential Defects in Cardiac Lineage Commitment and Maturation Cause Hypoplastic Left Heart Syndrome. Krane M*, Dreßen M*, Santamaria G*, My I*, Schneider CM*, Dorn T*, Laue S*, Mastantuono E, Berutti R, Rawat H, Gilsbach R, Schneider P, Lahm H, Schwarz S, Doppler SA, Paige S, Puluca N, Doll S, Neb I, Brade T, Zhang Z, Abou-Ajram C, Northoff B, Holdt LM, Sudhop S, Sahara M, Goedel A, Dendorfer A, Tjong FVY, Rijlaarsdam ME, Cleuziou J, Lang N, Kupatt C, Bezzina C, Lange R, Bowles NE, Mann M, Gelb BD, Crotti L, Hein L, Meitinger T, Wu S, Sinnecker D, Gruber PJ§, Laugwitz KL§, Moretti A§. Circulation (2021) *equal contribution, §corresponding authors
Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy. Moretti A§, Fonteyne L, Giesert F, Hoppmann P, Meier AB, Bozoglu T, Baehr A, Schneider CM, Sinnecker D, Klett K, Fröhlich T, Rahman FA, Haufe T, Sun S, Jurisch V, Kessler B, Hinkel R, Dirschinger R, Martens E, Jilek C, Graf A, Krebs S, Santamaria G, Kurome M, Zakhartchenko V, Campbell B, Voelse K, Wolf A, Ziegler T, Reichert S, Lee S, Flenkenthaler F, Dorn T, Jeremias I, Blum H, Dendorfer A, Schnieke A, Krause S, Walter MC, Klymiuk N, Laugwitz KL, Wolf E, Wurst W§, Kupatt C§. Nature Medicine (2020) §corresponding authors
Interplay of cell-cell contacts and RhoA/MRTF-A signaling regulates cardiomyocyte identity. Dorn T, Kornherr J, Parrotta EI, Zawada D, Ayetey H, Santamaria G, Iop L, Mastantuono E, Sinnecker D, Goedel A, Dirschinger RJ, My I, Laue S, Bozoglu T, Baarlink C, Ziegler T, Graf E, Hinkel R, Cuda G, Kääb S, Grace AA, Grosse R, Kupatt C, Meitinger T, Smith AG, Laugwitz KL§, Moretti A§. EMBO J. (2018) §corresponding authors
Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy. Gramlich M*§, Pane LS*, Zhou Q*, Chen Z, Murgia M, Schötterl S, Goedel A, Metzger K, Brade T, Parrotta E, Schaller M, Gerull B, Thierfelder L, Aartsma-Rus A, Labeit S, Atherton JJ, McGaughran J, Harvey RP, Sinnecker D, Mann M, Laugwitz KL, Gawaz MP, Moretti A§. EMBO Molecular Medicine (2015) *equal contribution, §corresponding authors
Isogenic human pluripotent stem cell pairs reveal the role of a KCNH2 mutation in long-QT syndrome. Bellin M§, Casini S, Davis RP, D'Aniello C, Haas J, Ward-van Oostwaard D, Tertoolen LGJ, Jung CB, Elliott DA, Welling A, Laugwitz KL, Moretti A§, Mummery CL. EMBO J. (2013) §corresponding authors
Patient-specific induced pluripotent stem cell models for long-QT syndrome. Moretti A, Bellin M, Welling A, Jung CB, Lam JT, Bott-Flügel L, Dorn T, Gödel A, Höhnke C, Hofmann F, Seyfarth M, Sinnecker D, Schömig A, Laugwitz K-L. New England Journal of Medicine (2010)
Multipotent embryonic Isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Moretti A*, Caron L*, Nakano A*, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR. Cell (2006) *equal contribution
Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Laugwitz K-L*, Moretti A*, Lam J, Gruber P, Yinhong Chen, Woodard S, Lin L-Z, Cai C-L, Lu M, Reth M, Platoshyn O, Yuan J, Evans S§, Chien KR§. Nature (2005) *equal contribution, §corresponding authors
Full publication list: PubMed, Google Scholar
European Research Council (ERC), ERC Advanced Grants BIOCARD & EPICURE
European Health and Digital Executive Agency, HORIZON-HLTH-DISEASE Grant GEREMY
German Research Foundation (DFG), Transregional Research Unit 152 & 267
Federal Ministry of Education and Research (BMBF), C-NATM Cluster
German Centre for Cardiovascular Research (DZHK), Munich Heart Alliance
Innovation Fund of the German Centres for Health Research (DZG)
Prof. Dr. Alessandra Moretti
Chair of Regenerative Medicine in Cardiovascular Diseases
amoretti(at)mytum.de
Lab address:
Klinikum rechts der Isar
Technische Universität München
Klinik und Poliklinik für Innere Medizin I
Ismaninger Straße 22
81675 Munich
Germany