General research interest
Soft Tissue Calcification
Abnormal mineralization in the middle sized arteries and in other soft tissues can be due to mutations in the ABCC6 gene encoding an ABC transporter or in the ectonucleotide pyrophosphatase ENPP1 gene. Mutations in either gene can cause pseudoxanthoma elasticum (PXE, OMIM 264800) or generalized arterial calcification of infancy (GACI, OMIM 208000). The expression pattern of ENPP1 is wider than that of ABCC6, but both proteins are expressed in the liver at high levels and are localized to the basolateral plasma membrane of hepatocytes. Mendelian disorders are associated to these two genes. PXE is characterized by severe skin, eye and arterial manifestations, while the very rare GACI causes severe prenatal aortic calcification with a high mortality rate. GACI and PXE represent two extremes of clinical spectrum of calcification disorders. In spite of the intensive international collaborative research efforts in which our group plays an important role, currently there is no therapy for these conditions. These disorders serve as models for the understanding of the pathomechanism of arterial calcification for a wide range of distinct diseases including more frequent clinical phenotypes such as “acquired” macular degeneration, β-thalassemia, vascular calcification (sometimes leading to coronary artery disease or stroke), uremia, and other rare calcification disorders.
The focus of our research is to find and test future therapeutics for these rare diseases in preclinical mouse models.
Covalent modifications of the chromatin are called epigenetic modifications. These modifications regulate the activity of the different parts of our genome and participate thereby to gene expression and cellular differentiation. Tamás Arányi is a senior research fellow (assoc. professor), who started research by studying the transcriptional regulation of genes of high medical relevance, tyrosine hydroxylase and later ABCC6, both associated with various diseases. He became immediately interested in the role of epigenetic modifications and their role in the regulation of the target genes. He also set up some tools used since in epigenetic research. Tamas demonstrated the functional role of epigenetic modifications in the regulation of the studied genes.
His research focus progressively turned recently to the study of the dynamic nature of epigenetic modifications (mainly DNA methylation) and the role of environmental stress in altering global epigenetic landscape. These environmental factors, for example viral infection or nutritional challenges are part of our everyday life. The discovery of their influence on our epigenetic profiles will participate in understanding the molecular mechanisms of the long-term effects of the various environmental stress factors often accompanied by major clinical relevance like obesity, hypertension or cancer.
- Department of Cell and Molecular Biology, University of Hawai’ (USA)
- Department of Deramatology, Th. Jefferson University, Philadelphia (USA)
- PXE International, Bethesda (USA)
- The Netherlands Cancer Institute (Holland)
- Angers University Hospital, Angers (France)