Prof. Dr. med. Monika U. G. v. Düring Research overview

 The integral membrane protein stomatin

- its role in organogenesis, haemolytic anemia and tumorigenesis.

Stomatin is a 32 kDa integral and lipid raft associated membrane protein that was first characterized in human red blood cells. Experimental data support the hypothesis that stomatin might play a fundamental role in the control of the surface expression of membrane proteins. Attention was drawn to this protein by its deficiency in the red blood cell membrane in the dominantly-inherited haemolytic anemia, hereditary stomatocytosis, in which the red cell membrane shows a leak to the monovalent cations Na+ and K+. The typical mouth-shaped (stoma) phenotype of the pathological red cells coined the name of the affected protein „stomatin“. Most patients have a low-grade anemia punctuated by recurrent episodes of more severe anemia (e.g. haemolytic crisis) and jaundice. Beside the classical form we recently characterized a further subtype the cryohydrocytosis.

Hematology. Up to now no mutation was found in the stomatin gene. The deficiency of stomatin in the red cell membrane is presumably the result of a mutation in another gene encoding interacting partner proteins. Therefore the hereditary stomatocytosis is an excellent clinical example reflecting the complex interaction of cellular proteins.

Developmental biology. Our experimental results revealed that stomatin is widely distributed in human tissues. Stomatin is early expressed during human ontogenesis and plays an important role in organ development and maturation. There is clinical evidence that under certain conditions the deficiency of stomatin in the red cell membrane can be associated with a failure of organ development.

Oncology. We found quantitative and qualitative changes in the cellular distribution pattern of stomatin-immunoreactivity in adenocarcinomas of lung and colon. The characteristic pattern of stomatin-immunoreactivity in the tumor tissue might reflect the interaction of the tumor with the adjacent tissue components.

Aim of our research: In our collaborative approach we intend to elucidate the role of stomatin in normal cells and under pathological conditions with a particular focus on morphological, physiological, developmental and molecular biological aspects.

Collaborators:

GordonStewart
University College London, UK
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Steve Parsons/David Anstee
International Blood Group Reference Laboratory,
Bristol, UK
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Achille Iolascon
Dipartimento di Biomedicina dell´Età Evolutiva
Università degli studi di Bari, ItalyK
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K.-M. Müller
Institut für Pathologie,
Ruhr-Universität Bochum
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G. Knöpfle
Zentrum für Pathologie,
Universität Bonn
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U. Gembruch
Abteilung für Pränatale Diagnostik und Therapie,
Universität Bonn
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