In humans, ~30% of the developing embryos terminate before implantation, and about 25% fail during the transition from gastrulation to organogenesis when cell fate and identity are set. The failure to specify cell fate and identity in a timely and robust manner results in developmental abnormalities and diseases. For example, 1 out of 100 children are born with congenital cardiac diseases, for the majority of which the causes are unknown. The Kurian lab investigates the regulatory principles that govern cell fate and identity during human cardiac development, homeostasis, and pathomechanisms of cardiac aging.
The heart is the first organ to form and function during embryogenesis. The development of the heart is carefully choreographed by a series of precisely controlled cell fate decisions, which enables cardiac morphogenesis. A systematic understanding of molecular regulation of cardiac fate and identity is essential not only to understand the principles of self-organization of the human heart but also to develop therapeutic interventions for congenital and adult-onset cardiac disease. Our current understanding of the molecular regulation of cell fate and identity is mainly based on morphogen-mediated signal transduction, epigenetic, and transcriptional mechanisms. However, RNA is the primary language of communication from the genome, and it is distinctly regulated at each stage of its life cycle. We are only beginning to understand the RNA regulatory principles that govern cell fate decisions and cellular identity. Our lab is focused on understanding the RNA-centric processes (controlled by RNA binding proteins, non-coding RNAs, and regulatory motifs embedded in primary transcripts and mRNAs) and their regulatory logic that program cardiac cell fate and identity during human embryogenesis. In parallel, we study how the breakdown of RNA regulatory processes causes congenital and age-associated cardiac diseases. In close collaboration with the industry, we are developing personalized, non-immunogenic RNA therapeutics for congenital cardiac diseases.
Our long-term mission is to gain a systems-level understanding of the RNA regulatory principles that shape the self-organization and homeostasis of tissue and organs in humans in order to develop therapeutic solutions for tissue/ organ regeneration
The key questions we address are:
We employ pluripotent stem cells and cell fate engineering (2D differentiation and organoid models) in combination with systems biology and genome editing approaches to reconstruct and investigate human cardiac development and disease.
Prof. Eric Van Nostrand, Baylor College of Medicine, USA
Prof. Michael Petrascheck, Scripps Research Institute, USA
Prof. Leos Shivaya Valasek, Czech Academy of Sciences, Czech Republic
Dr. Sasha Mendjan, Institute of Molecular Biotechnology, Vienna, Austria
Prof. Argyris Papantonis, University of Gottingen, DE
Prof. Malte Gather & Prof. Marcel Schubert, Humboldt Centre for Nano- and Biophotonics, University of Cologne
Prof. Christian Frezza, CECAD, Cologne
Prof. Dr. Aleksandra Trifunovic, CECAD, Cologne
Prof. Dr. Miguel A. Alejandre Alcázar, Faculty of Medicine, University of Cologne
Dr. Ina Huppertz, MPI-AGE, Cologne
Loss of transcriptional control has been proposed as a causal link to cardiac ageing. We discovered that DHS is a key molecular driver of age-associated cardiac episodes in humans by mediating the loss of transcriptional control.
A temporal decline in the functional and molecular integrity of an organism defines its ageing process. While multiple hallmarks of ageing have recently been enumerated, our understanding of their functional, molecular and temporal hierarchy remains incomplete.
The significance of these hallmarks in the ageing process vary in a tissue/ cell type specific manner. Considering the physiological differences between organs, it is conceivable that their susceptibility to these distinct triggers of ageing can differ. Therefore, it is important to delineate those mechanisms that influence the ageing process of specific organs to better understand organismal ageing. We investigate evolutionarily conserved mechanisms that leads to aging of the heart.
We envision to
Laboratory for Developmental and Regenerative RNA Biology - Dr. Leo Kurian
Center for Molecular Medicine Cologne | Institute for Neurophysiology | CMMC Research Building
CMMC - PI - A 07
CMMC - PI - assoc. JRG 01
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Center for Molecular Medicine Cologne | Institute for Neurophysiology | CMMC Research Building
Robert-Koch-Str. 21
50931 Cologne
Deniz Bartsch, PostDoc
Kalamkar Kaustubh, PhD student
Nachiket Pathek, PhD student
Mattias König, PhD student
Christoph Walter, Master student
Andre Müller, Master student
Ayben Kakıcı, Bachelor student
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Prof. Dr. med. Thomas Benzing
Chair of the CMMC
