We investigate disease-associated genes and epigenetic modulators in the genomic, transcriptomic and proteomic context. We have identified the transcription factor CITED2 as a human disease gene and characterized the chromatin factor DPF3, the first protein shown to bind histone acetylation and methylation marks via its PHD domain.
Moreover, we study transcription networks underlying heart development and showed the interplay between multiple cardiac transcription factors and histone modifications. Finally, we demonstrated the polygenic origin of Tetralogy of Fallot by introducing a novel computational approach to identify disease-related genes.
Our long-term goal is to combine knowledge of molecular etiologies and mechanisms to improve preventive and therapeutic opportunities for patients with congenital heart diseases.
Experimental and Clinical Research Center
Cardiovascular Genetics/AG Prof. Sperling
Lindenberger Weg 80
Phone +49 30 450 540122 (secretary)
Secretary office hours: Monday, Tuesday and Thursday 8:00 a.m. - 2:00 p.m (CET)
The office of Silke Sperling and her secretary as well as the bioinformatics group are located on the 2nd floor of building 46. The laboratories are located in the basement of building 50.
Prof. Dr. Silke Rickert-Sperling
- Full-professor for Cardiovascular Genetics at the Charité - Universitätsmedizin Berlin
- Coopted professor at the Faculty of Biology, Chemistry and Pharmacy of the Freie Universität Berlin
Phone: +49 30 450 540123
Prof. Dr. Silke Rickert-Sperling holds a doctoral degree in cardiac physiology and studied medicine from 1991 up to her full medical license in 1997. During her education she went from Berlin to New York, San Diego, Chicago, and Rochester. Afterwards she worked as a MD at the German Heart Center of Berlin.
In 1999, she began her postdoctoral research at the department of Prof. Dr. Lehrach at the Max Planck Institute for molecular genetics and there she became head of the research group “Cardiovascular Genetics” in 2001. She holds a habilitation in molecular biology and bioinformatics. In 2011, she was honored with a Heisenberg-Professorship and became full-professor for Cardiovascular Genetics at the Medical Faculty of the Charité in Berlin. She is coopted professor at the Faculty of Biology, Chemistry and Pharmacy of the Freie Universität Berlin. She leads an interdisciplinary research group (molecular biology and bioinformatics) at the ECRC. As guest scientist, she continues to collaborate with the Max Planck Institute for molecular genetics.
Her research activities focus on understanding the molecular basis of human cardiovascular disorders in particular congenital heart malformations and cardiac dysfunction. Using systems biology approaches, she studies cardiac (dys)development and muscle maturation in human and mice. She investigates a broader range of disease-associated genes and epigenetic modulators in the genomic, transcriptomic and proteomic context. She hopes to combine knowledge of molecular etiologies and mechanisms to eventually improve preventive and therapeutic opportunities for patients.
She is principal investigator and co-coordinator of various European efforts (HeartRepair, CardioGeNet, and CardioNeT) and principal investigator of the Berlin Institute of Health (BIH). She was board member of the European Society of Human Genetics and is Fellow of the European Society of Cardiology (ESC) as well as board member of the ESC Working Group on Development, Anatomy and Pathology.
Privately, she is married to Dr. Andreas M. Rickert and has two daughters.
Phone: +49 30 450 540122
Fax: +49 30 450 540159
Technical assistant in the lab
Phone: +49 30 450 540168
Technical assistant in the lab
Phone: +49 30 450 540168
Dr. Marcel Grunert
Research Scientist in Bioinformatics with focus on high-throughput genomics and systems biology
Phone: +49 30 450 540153
Dr. Georg (Geo) Vogler
Research scientist in our group and in the (Sanford Burnham Prebys Medical Discovery Institute in La Jolla, CA, USA)
Dr. Emilie Plantié
Postdoctoral Researcher in Genetics and Developmental Biology
Phone: +49 30 450 540135
PhD student in Bioinformatics
Phone: +49 30 450 540154
PhD student in Biology
Phone: +49 30 450 540135
PhD student in Biology
Phone: +49 30 450 540149
Students (Dipl, MA, BA, Asst)
Master student in Bioinformatics
Prof. Dr. Rolf Bodmer
- Einstein BIH Visiting Fellow
- Professor and Program Director of the Development and Aging Program in the Neuroscience, Aging and Stem Cell Research Center at the Sanford Burnham Prebys Medical Discovery Institute (La Jolla, CA, USA)
|Dr. Huanhuan Cui||PhD (2011-2016), Postdoc (2016-2017)|
|Andreas Perrot||Research assistant (2012-2016); ECRC/Charité|
|Sophia Schönhals||PhD student (2013-2016); Malvern Instruments|
|Katja Birker||Trainee (2016), PhD student in Bodmer lab|
|Sadaf Vahdat||Guest PhD student (2016); Technion - Israel Institute of Technology|
|Jasmina Czery||BSc student (2016)|
|Dr. Katherina Bellmann||PhD (2011-2015)|
|Dr. Vikas Bansal||PhD (2011-2015)|
|Dr. Cornelia Dorn||Student assistant (2008), Dipl student (2009), PhD (2010-2015), Postdoc (2015); Sanofi|
|Katharina Stenin||PhD student (2014-2015); Metanomics|
|Dr. Elena Cano Rincon||Postdoc (2014-2015); Max Delbrück Center for Molecular Medicine (MDC)|
|Ashley Cooper||Research assistant (2015); The Lancet|
|Gizem Spriewald||BSc student (2015)|
|Michael Mücke||Trainee (2014); Max Delbrück Center for Molecular Medicine (MDC)|
|Dr. Sandra Schmitz||Postdoc (2012-2013); Max Planck Institute for Molecular Genetics|
|Nicole Zehetner||Trainee (2012)|
|Andrea Behm||Technical assistant (2012); ECRC/Charité|
|Dr. Siegrun Mebus||Associated Clinical Researcher; surgery in Eichwalde|
|Barbara Gibas||Secretary (until 2012)|
|Dr. Jenny Schlesinger||Student assistant (2005-2007), Dipl student (2007-2008), PhD (2008-2011), Postdoc (2012); Charité|
|Dr. Markus Schüler||Student assistant (2005-2006), MSc student (2006), PhD (2007-2011), Postdoc (2012); eBay mobile.de|
|Sascha Werner||Trainee (2011)|
|Susanne Thomsen||Technical assistant (2011)|
|Ilona Dunkel||Technical assistant (2002-2011); Max Planck Institute for Molecular Genetics|
|Lucas Rudiger||PhD student (2009-2010); Max Delbrück Center for Molecular Medicine (MDC)|
|Michalina Mankowska||Dipl student (2009-2010)|
|Dr. Qin Zhang||PhD (2008-2010); DKFZ|
|Jörn Bethune||Trainee (2009)|
|Julia Kofent||PhD student (2009); Max Delbrück Center for Molecular Medicine (MDC)|
|Dr. Martje Tönjes||PhD (2006-2009), Postdoc (2009); DKFZ|
|Dr. Andreja Brodarac||Postdoc (2008-2009)|
|Dr. Martin Lange||PhD (2003-2008); Bayer AG|
|Dr. Jenny J. Fischer||PhD (2004-2008); Metanomics (BASF)|
|Katharina Rost||PhD student (2007-2008)|
|Dr. Alan Matthew Punnoose||Postdoc (2006-2007)|
|Katja Stirl||Dipl student (2006-2007)|
|Tammo Krüger||Computer scientist (2006-2007)|
|Dr. Christina Grimm||Postdoc (2002-2006)|
|Philip Tomann||Dipl student (2006)|
|Dr. Steanie Hammer||Postdoc (2004-2006)|
|Kathrin Stoßberg||Guest (2005-2006)|
|Raffaello Galli||Computer scientist (2004-2005)|
|Dr. Bogac Kaynak||PhD (2001-2005)|
|Christoph Müller-Vahl||Trainee (2005-2006)|
|Dirk Paul||Trainee (2005)|
|Antje Purmann||BSc student (2005)|
|Silke Grabow||Dipl student (2004-2005)|
|Dr. Dominik Seelow||PhD student (2000-2004); Charité|
|FH-Prof. Dr. Katrin Bach||Dipl student (2003-2004); Management Center Innsbruck|
|Jan-Hinnerk Vogel||MSc student (2003-2004)|
|Dr. Andreas Rickert||Postdoc (2003); PHINEO|
|Dr. Martin Hillebrand||Postdoc (2003)|
|Denis Bauer||Trainee (2002)|
|Katrin Bach||Trainee (2002)|
|Daniel Rawer||Trainee (2002)|
|Anja Angelov||Trainee (2000,2001-2002)|
|Dr. Frank Wittchen||PhD student (2000)|
|Tim Herrmann||Trainee (2000)|
|Dr. Olaf Bender||Postdoc (1999-2000); KKS Charité|
|Dr. Nidar Asfar||MD student (1998-1999); surgery in Berlin|
Single Nucleotide Variations in Tetralogy of Fallot
Congenital heart diseases (CHD) are the most common birth defect in human and affect nearly 1% of all newborns. They are a heterogeneous group of disorders ranging from minor alterations to complex malformations requiring multiple surgeries. The majority of CHDs are probably caused by a combination of multiple genetic, epigenetic and environmental factors.
The identification of disease-related genes has been a great challenge and is complicated by the fact that every healthy human carries hundreds of probably damaging genomic variations that seem to be tolerated in the individual context.
We aimed to unravel the complex genetics of Tetralogy of Fallot (TOF), the most common cyanotic form of CHD, and to develop novel methods for the identification of disease-related genes. Focusing on single nucleotide variations, we developed the novel concept of the gene mutation frequency (GMF), which considers all deleterious variations in a gene and can determine over-mutated genes in a patient cohort in comparison to control individuals.
This provided strong evidence for the polygenic origin of TOF and identified 16 significantly over-mutated genes affected by combinations of deleterious private and rare mutations. The genes interact in a molecular network and show sustained expression in the adult heart, which might help to understand differences in long-term clinical outcomes of TOF patients.
A detailed description of the GMF approach can be found here.
Copy Number Variations in Tetralogy of Fallot
We developed a novel method to identify copy number variations (CNVs) based on outlier detection applicable to small cohorts, which is of particular interest for the discovery of individual CNVs within families, de novo CNVs in trios and/or small cohorts of specific phenotypes like rare diseases.
In both HapMap control samples and TOF cases, our method is superior to the tool CoNIFER, such that it identifies more true positive CNVs. Finally, we found four copy number gains affecting important cardiac regulators in the TOF patients.
Cardiac and skeletal muscle development is a finely tuned process that requires a precise control of gene expression, which is regulated by the interplay of transcription factors, histone modifications and chromatin remodeling complexes.
Studying murine cardiomyocytes, we could show the interdependency of key cardiac transcription factors (Gata4, Mef2a, Nkx2.5, and Srf), activating histone modifications (H3ac, H4ac, H3K4me2, and H3K4me3) and microRNA expression. However, it is widely unknown which impact the exact position of histone marks (relative to the transcription start site) has on cardiac and skeletal muscle gene expression.
To elucidate this question, we determined the genomic binding profiles of three histone marks as well as the RNA expression in murine myoblasts and differentiated myotubes. Computational analysis and integration of the data showed that a position-dependent profile of histone modifications marks muscle tissue specific genes, which will hopefully enhance our understanding of muscle maturation.
Together with the Einstein BIH Visiting Fellow Prof. Dr. Bodmer (SBMRI in La Jolla, CA, USA) we established a gene discovery program in the Drosophila model to test and validate genes and pathways, which we found associated with congenital heart disease (CHD) in our patient genomic screens. In particular, we focus on genes potentially causative for Tetralogy of Fallot (TOF, Grunert et al. 2014 and 2016).
Congenital heart diseases are the most common defect present in almost 1% of all human births, which in adults often results in undefined cardiac insufficiencies and arrhythmia long-term. Despite its prevalence and impact on society, our ability to identify the etiology of most CHD cases is limited. There is a great unmet need to understand the genetic mechanisms leading to developmental defects to counter the long-term clinical threats.
By using CHD patient genomic information, we aim to identify relevant novel genes that lead to CHD pathogenesis. We hope to achieve this by modeling patient-derived genetic aberrations and potentially damaging variants in the genetically versatile Drosophila model with a heart of remarkably conserved properties and controls. The significance of this project lies in the efficient discovery of new CHD genes, their polygenic interactions, mechanisms of action and placement in interlinked pathways – in vivo. The discoveries should ultimately be for the benefit of personalized patient care.
Information for Students
We always offer a number of different bachelor and master thesis in our lab and in the bioinformatics group. If you are a student of biology / biochemistry / biotechnology / bioinformatics and interested, please contact us.
We also offer medical students to perform a doctoral thesis in the laboratory. At least one semester free time without lectures and courses (Freisemester) is a prerequisite.
If you are looking for a PhD student position or a postdoc position, applications are always welcome.