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RhoGTPasen und Tumorincasion: Mechanismen und Netzwerke

Name und Adresse:

Prof. Dr. Reza Ahmadian, Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

Schwerpunkt 1:

Basic molecular and cellular principles

Titel des Forschungsprojektes:

Perspectives of RAS and RHO signaling in human diseases


Extensive research on RAS- and RHO-like proteins over the past 30 years has led to numerous insights into their cellular functions in the context of various human cancers. However, the involvement of these proteins is not only implicated in human malignancies but also in a class of developmental disorders, known as RASopathies, which constitute a family of rare diseases affecting development and growth. These disorders include Noonan syndrome and an increasing number of clinically related conditions sharing dysregulation of RAS signaling as common pathogenetic mechanism. Major features include growth retardation, congenital heart disease, hypertrophic cardiomyopathy, cognitive deficits, facial dysmorphism, learning difficulties, skeletal and hematologic anomalies, and variable predisposition to certain malignancies. Despite great advances in our understanding of the molecular and cellular mechanisms, the large number of uncharacterized proteins of the RAS and RHO families as well as their regulators and effectors along with the complexity of the signaling pathways indicate that much remains to be learnt. Goals of our research are to explore further the molecular bases of these disorders through understanding the molecular link between dysregulated signaling and the pathogenesis of the disorder, guiding future work directed to a mechanism-based identification of novel targets for therapeutic interventions, and validating compounds to restore appropriate RAS signaling extent as a new approach for the development of therapeutic interventions to ameliorate evolutive complications of these diseases.