Regenerative Medicine of Cardiovascular Diseases
(Deutsch: Lehrstuhl für Regenerative Medizin kardiovaskulärer Erkrankungen)
Regenerative therapies, either by transplantation of stem cells or stem cell-derived differentiated cells into the defective organ or by promoting endogenous regenerative processes, are an important goal of cardiovascular research. However, to successfully translate these concepts into patient care, several fundamental research questions have to be answered, and many problems have to be solved. One core activity of this group is to address such questions with state-of-the-art methods.
Research
Cardiovascular disorders account today for about 30% of deaths world wide. An urgent need in cardiovascular medicine is to develop novel therapeutic tools and approaches to restore proper function of diseased hearts and to regenerate cardiac muscle after injury. Latest discoveries and advanced knowledge in the fields of stem cell biology, developmental cardiology, and genome editing hold great promise for achieving this goal.
Methods
- Generation, culture and differentiation of human pluripotent stem cells
- Genetic modification (CRISPR/Cas system)
- Optical physiological characterization of cardiomyocytes (Calcium imaging, membrane potential imaging, second messenger imaging)
- Three-dimensional culture of iPS-derived cardiomyocytes enabling measurements of contractility and intracellular calcium
- Gene expression analysis (RNAseq, single-cell RNAseq)
- Molecular cloning, routine molecular biology methods
- Western blot, immune fluorescence, co-immuneprecipitation
- Cell injection into murine embryos (in utero and ex utero)
- Prof. Dr. Alessandra Moretti
Chair of Regenerative Medicine of Cardiovascular Diseases, group leader - Dr. Tatjana Dorn
Senior scientist (developmental biology, lineage decision) - Dr. Daniel Sinnecker
Senior scientist (cardiac disease modelling, physiology) - Jessica Haas
Postdoc - Maria Teresa De Angelis
PhD, postdoc - Gianluca Santamaria
PhD, postdoc - Dr. Ralf Dirschinger
Physician scientist - Dr. Johannes von Burstin
Physician scientist - Dr. Mark Lachmann
Physician scientist - Dr. med. univ. Christine Schneider
Physician scientist - Dorota Zawada
PhD student - Fangfang Zhang
PhD student - Anna Meier
PhD student - Christina Scherb
Technician - Birgit Campbell
Technician
Scientific Projects:
We regularly offer projects for diploma, PhD and M.D. students.
Third-Party Funding:
- European Research Council
- German Research Foundation
- German Centre for Cardiovascular Research, Munich Heart
Alliance
- Else Kröner-Fresenius Foundation
Original work
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. (2018) Interplay of cell-cell contacts and RhoA/MRTF-A signaling regulates cardiomyocyte identity. EMBO J 37:pii: e98133.
Chen Z, Xian W, Bellin M, Dorn T, Tian Q, Goedel A, Dreizehnter L, Schneider CM, Ward-van Oostwaard D, Ng JK, Hinkel R, Pane LS, Mummery CL, Lipp P, Moretti A, Laugwitz KL, Sinnecker D. (2017) Subtype-specific promoter-driven action potential imaging for precise disease modelling and drug testing in hiPSC-derived cardiomyocytes. Eur Heart J 38:292-301.
Rocchetti M, Sala L, Dreizehnter L, Crotti L, Sinnecker D, Mura M, Pane LS, Altomare C, Torre E, Mostacciuolo G, Severi S, Porta A, De Ferrari GM, George AL Jr, Schwartz PJ, Gnecchi M, Moretti A, Zaza A. (2017) Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes. Cardiovasc Res 113:531-541.
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. (2015) Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy. EMBO Mol Med 7:562-76.
Dorn T, Goedel A, Lam JT, Haas J, Tian Q, Herrmann F, Bundschu K, Dobreva G, Schiemann M, Dirschinger R, Guo Y, Kühl SJ, Sinnecker D, Lipp P, Laugwitz KL, Kühl M, Moretti A. (2015). Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity. Stem Cells 33(4):1113-29.
Jung CB, Moretti A, Schnitzler MM, Iop L, Storch U, Bellin M, Dorn T, Ruppenthal S, Pfeiffer S, Goedel A, Dirschinger RJ, Seyfarth M, Lam JT, Sinnecker D, Gudermann T, Lipp P & Laugwitz K-L (2012). Dantrolene rescues arrhythmogenic RYR2 defect in a patient-specific stem cell model of catecholaminergic polymorphic ventricular tachycardia. EMBO Mol. Med. 3:180-191.
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 (2010). Patient-specific induced pluripotent stem cell models for long-QT syndrome. N. Engl. J. Med. 363: 1397-409.
Qyang Y, Martin-Puig S, Chiravuri M, Chen S, Xu H, Bu L, Jiang X, Lin L, Granger A, Moretti A, Caron L, Wu X, Clarke J, Taketo MM, Laugwitz K-L, Moon RT, Gruber P, Evans SM, Ding S & Chien KR (2007). The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/β-catenin pathway. Cell Stem Cell 1: 1-15.
Moretti A, Caron, L, Nakano, A, Lam, JT, Chen, Y, Qyang, Y, Sasaki, M, Yunfu, S, Evans, S, Laugwitz, K-L & Chien KR (2006). Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127: 1151-1166.
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 (2005). Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433: 647-653.
Book chapters, Reviews and Editorials
Sinnecker D, Moretti A. (2018) Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Towards Personalized Therapeutic Strategies? In: Dierk Thomas, Carol Ann Remme (Eds.) Channelopathies in Heart Disease. Springer International Publishing, ISBN 978-3-319-77811-2.
Sinnecker D, Laugwitz KL, Moretti A. (2014) Induced pluripotent stem cell-derived cardiomyocytes for drug development and toxicity testing. Pharmacol Ther 143:246-52.
Moretti A, Laugwitz KL, Dorn T, Sinnecker D, Mummery C. (2013) Pluripotent stem cell models of human heart disease. Cold Spring Harb Perspect Med 3. pii: a014027.
Evans SM, Moretti A & Laugwitz KL (2010). MicroRNAs in a cardiac loop: progenitor or myocyte? Dev. Cell 19: 787-8.
Laugwitz K-L, Moretti A, Nakano A & Chien KR (2008). Islet-1 Cardiovascular Progenitors: A single source for heart lineages? Development 135: 193-205.
Chien KR, Moretti A & Laugwitz K-L (2004). ES cells to the Rescue. Science 306: 239-240.
Prof. Dr.
Alessandra Moretti
Lehrstuhl für Regenerative Medizin kardiovaskulärer Erkrankungen, Gruppenleitung
Telefon 089 4140 2350
E-Mail