Institut für Neurophysiologie
AG Dr. Leo Kurian
We investigate how cellular identities are programmed and reprogrammed during development. During embryonic development, pluripotent stem cells acquire defined progenitor identities culminating in the generation of terminally differentiated cell types. This process is orchestrated by the precise temporal regulation of genes that program developmental decisions until lineages become segregated and cellular identities are ﬁxed. Of the many factors that influence cell fate, long non-coding RNAs (lncRNAs) are emerging as important regulators in development and differentiation. This newly discovered class of non-coding RNA is believed to be critical to orchestrating key molecular events in development on the transcriptional, epigenetic, and post-transcriptional levels. Our mission is to gain a deeper understanding of the functional impact and molecular mechanisms of lineage-specific lncRNAs on cardiac development and regeneration. Using both whole-organism (zebrafish) and human stem cell model systems we intend to gain molecular insights into the developing heart.
AG Dr. Filomain Nguemo
Nguemo´s scientific work aims at better understanding of the networks controlling cell specification (e.g. cardiomyocytes) and improving the physiological understanding of the developing and diseased heart. His major research work includes the usage of electrophysiology techniques to characterize the change of cardiac function and the modulation by drugs, measuring Ca2+ homeostasis and transients of single cardiac cells and signalling pathways involved in heart failure and arrhythmogenesis. His work also focuses on pharmacological screening for the cardiac action of drugs based on large-scale testing using embryonic stem (ES), induced pluripotent(iPS) cell-derived cardiomyocytes and myocardial slices (e. g. from human origin), which provide a single, human-based model to access electrophysiological, biochemical and viability cytotoxic endpoints under acute and longer-term exposures.
Expertise and facilities:
- Stem cells biology and their differentiation to the cardiac and vascular lineages
- Biology of heart development and cardiac disease
- Electrophysiology of cardiac cells and neurons by patch clamp, voltage sensitive dyes, impedance as well as microelectrode arrays (MEAs) and their use in drug safety testing.
- Calcium handling and electrical activity in cardiac cells and neurons
- State of the art cell culture laboratories, slicing techniques, cell imaging, electrophysiology (Patch-clamp, impedance assays, microelectrode arrays and fluorescence imaging)
- Stem cells differentiation and maturation protocols
AG Dr. rer .medic. Kurt Pfannkuche
The focus of the research group is cardiac cell replacement therapy & cardiac tissue engineering. The group leader Kurt Pfannkuche, born 1976 in Germany, studied biology with a focus on ecology, genetics, animal physiology and pharmacology at the University of Cologne. His scientific career started in the laboratory of the renowned immunologist Klaus Rajewsky with a project on genetically engineered cell-permeable Cre-recombinase. He continued his scientific work at the Institute for Neurophysiology at the University of Cologne specializing in the cardiac development of stem cells. http://www.cardiac-tissue-engineering.eu/
AG Prof. Dr. Agapios Sachinidis
My actual and future research efforts will be focused on the molecular genetics and genomics of embryonic stem cells (ESCs), inducible pluripotent stem (iPS) cells, cells of cardiovascular system (stem cell cardiovascular genomics). Specifically, we are focusing on the following research areas: 1) the functional analysis of transcripts of unknown functions applying “gain of function” and “loss of function” molecular biology methodologies in transgenic ESCs and iPS cells as well as in transgenic zebrafish models 2) the selective differentiation of ESCs and iPS cells using different small molecules to different the cells into specific somatic cell types including neurons and cells of the cardiovascular system 3) monitoring developmental and cardiovascular toxicity gene signatures and pathways using reporter line technologies and 4) mimicking adaptation/toxicity processes in cardiovascular cell types applying “gain” and “loss” of function methodologies.
AG Dr. Dr. Tomo Šarić
Pluripotent stem cell-derivatives hold a great promise for tissue regeneration, human in vitro disease modelling and drug testing. The major goal of projects in Saric group is to differentiate pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), into their tissue-specific derivatives, such as cardiomyocytes and neural cells, and explore their potential for tissue repair and modeling of human diseases.
In the first research area, we use animal models of myocardial infarction to determine the ability of iPSC-derived cardiomyocytes to replace cells damaged in the infarct area. For this purpose, we employ various non-invasive in vivo imaging methods to monitor the fate of transplanted cells and test novel approaches to enhance their integration in the infracted heart. In a similar project, we are studying the ability of human iPSC-derived neural stem cells in combination with various supportive treatment modalities to repair traumatically injured brain in a rat model of this disease. Since the immune system is one of major determinants affecting the survival of transplanted cells, we also investigate immunological properties of ESC and iPSC-derivatives both in vitro and in vivo. Knowledge gained in these studies will help develop approaches to prevent cell rejection and improve their therapeutic effect.
In addition to our focus on tissue repair, we also work on establishing human iPSC-based in vitro models of inherited heart diseases, such as arrhythmias and cardiomyopathies. Methods used range from cell and molecular biology to gene editing and tissue engineering. The goal is to increase our understanding of the disease pathophysiology and establish cell-based assays for development of novel more potent drugs for these incurable diseases. To this end, the group is involved as one of the iPSC-Centers in generation of human disease-specific induced pluripotent stem cells (iPSCs) for the “European Bank of induced Pluripotent Stem Cells (EBiSC,https://www.ebisc.org/)”, which is a collaborative project jointly funded by the European Union and the Innovative Medicines Initiative. Cell lines generated in this project are developed under highly standardized conditions and are made available to all researchers worldwide in hope to facilitate use of these cell-based models for research of human diseases and development of better therapies for patients affected by them.
AG Prof. Dr. Toni Schneider
Channelopathies (Ionenkanal-Krankheiten) are caused by defects either in an ion conducting or an associated auxiliary subunit of the channel, or by interacting partners. We are focused on structure and function of a voltage-dependent Ca2+-channel containing the Cav2.3 E-type subunit, the formerly called “pharmacoresistant” (R-type) calcium channel. Its gene inactivation in mice has given us access to its physiological function which is related to the cardiac, the endocrine and the neuronal system.
Protein interaction partners of the voltage-gated Ca2+-channel proteins have been detected. They connect ion channel activity with cellular functions helping us to explore molecular mechanisms of channelopathies related to arrhythmia, hormone release dysfunction, and neuronal disorders like epilepsy.