NOV 17, 2016 03:00 AM PST

Genetic variability of ps-iPSC and related blood and fibroblasts - somatic mutations

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  • Professor, Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, Germany
      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 an 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 co-opted 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 contexts. 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 a board member of the European Society of Human Genetics and is Fellow of the European Society of Cardiology (ESC) as well as a board member of the ESC Working Group on Development, Anatomy and Pathology.


    The generation of induced pluripotent stem cells (iPSCs) from adult easily accessible somatic tissues was introduced ten years ago. This technology has revolutionized our opportunities to study human disorders including complex genetics and develop novel therapeutic concepts for regenerative medicine. By differentiating iPSCs to different cell types and stages, we can gain insights into developmental and disease driving molecular networks. Yet, a discussed question of the iPSC model system is the extent to which they retain residual phenotypes from their precursor, which impacts on the study of transcription networks. Moreover, it is open to which degree somatic mutations impact on functional studies of human genetic disorders when patient-specific iPSCs are applied. Here, we will tackle this question in the course of studying healthy and diseased siblings with Tetralogy of Fallot, a frequent congenital heart defect of multigenic origin. Routine genetic screenings are mainly based on genetic material derived from either whole blood or cheek swap sampling. ps-iPSCs are typically derived from dermal fibroblast (skin biopsies) or whole blood derived immortalized lymphoplastoid cell lines (LCLs). We will discuss whole genome frequency and impact of somatic acquired mutations on gene expression and functional studies of complex genetic disorders using ps-iPSCs.

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