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Molecular Medicine Partnership Unit |
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Team 3 |
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Iron homeostasis in health and disease
Factsheet [PDF]
Previous and current research
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| The iron cycle |
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Iron biology investigates how cells and organisms regulate their iron content, how tissues orchestrate
iron allocation and how dysregulated iron homeostasis leads to common haematological, metabolic
and neurodegenerative diseases.
One current research focus is on understanding the molecular mechanisms involved in hereditary
hemochromatosis [HH], one of the most common genetic disorders in the western world. The disease
is mainly caused by mutations in the HFE gene, which codes for a MHC class I-like molecule.
We previously demonstrated that HFE is required for appropriate hepatic expression of the iron hormone
and anti-microbial peptide hepcidin: expression of this negative regulator of duodenal iron
absorption and macrophage iron release is decreased and cannot be adjusted appropriately in
response to elevated hepatic iron levels and inflammatory stimuli in HFE-deficient mice and HH
patients. This links HFE to the immune system and to the anemia of chronic diseases [ACD], which
results in iron redistribution in response to inflammation, infection and malignancy.
To investigate whether HFE functions in hepatocytes or other cells communicating with them, we analyze
conditional knock-out mouse lines where HFE is deleted in duodenal enterocytes, macrophages
[incl. Kupffer cells] or hepatocytes. Analysis of systemic and cellular changes in iron parameters in
response to HFE deficiency will clarify the function of HFE in the different cell types tested.
In addition we assess signalling pathways involved in hepcidin regulation. We established a cellbased
assay that recapitulates HFE-dependent iron and/or LPS-mediated hepcidin regulation.
RNAi-based functional testing is used to validate and further dissect components of the regulatory
pathway.
Future projects and goals
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To understand the integration of signalling pathways involved in hepcidin regulation in response
to systemic signals like iron availability, hypoxia as well as inflammation and infection. |
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To understand molecular mechanisms and regulatory circuits to maintain physiological iron
homeostasis and its connection to the immune system applying genome-wide approaches. |
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To understand molecular mechanisms underlying frequent disorders of iron metabolism
including different |
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Based on our recent development of a novel microarray platform for genome-wide profiling of
mature miRNAs [miChip], we will investigate miRNA expression in different disease entities [in
cooperation with different partners], whereby a major focus will be on the analysis of the
different subtypes of childhood leukaemia. |
Members:
Prof. Dr. Matthias W. Hentze
Associate Director
European Molecular Biology Laboratory
Meyerhofstraße 1
69117 Heidelberg
Tel: +49 6221 387-8501 or 8502
Fax: +49 6221
387-8306
E-mail: matthias.hentze@embl.de
Group home page
Dr. Martina Muckenthaler
Head of Molecular Medicine
Department
of Pediatric Oncology, Haematology, Immunology and Pulmonology
Children's Hospital, University of Heidelberg
Im Neuenheimer Feld 153
69120 Heidelberg
Tel: +49 6221 566923
Fax: +49 6221 564559
E-mail: martina.muckenthaler@med.uni-heidelberg.de
Maria Vittoria Verga Falzacappa [PhD student]
Judit Kiss [PhD student]
Maria Carmen Sanchez-Fernandez [Postdoc]
Mingang Zhu [Postdoc]
Maja Vujic [Postdoc]
Mirco Castoldi [Postdoc]
Jens Stolte [research technician]
Stefanie Martinache [research technician]
Beata Glowacka [PhD student]
Link to Children's Hospital, University of Heidelberg |
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