Prof. Dr. Martina Muckenthaler
Head of Molecular Medicine, Center for Child and Adolescent Medicine
Div. Pediatric Oncology, Immunology, and Hematology
University Clinic Heidelberg
Im Neuenheimer Feld 350
D- 69120 Heidelberg
Every year millions of patients worldwide are affected by iron metabolism defects. Our knowledge about these diseases is still incomplete and the treatment strategy is often unclear. At one end of the spectrum is anemia, often caused by iron deficiency.
The Group "Muckenthaler", which belongs to the Department of Pediatric Oncology, Hematology, Immunology and Pulmonology (Prof. Kulozik) of the University Hospital Heidelberg, deals with diseases of iron metabolism and the underlying regulatory mechanisms.
We are particularly interested in the rare group of congenital anemias, for which we have been able to improve diagnostics and therapy in recent years. We identified genetic defects and investigate the resulting pathogenesis in cell and animal models. At the other end of the spectrum are common iron overload disorders, such as hereditary hemochromatosis. Here, the iron accumulation in various organs causes, among other things, liver damage, heart disease and impairments of the endocrine system. Since both iron deficiency and excess iron affect our health, we are interested in molecular mechanisms that regulate iron metabolism. Of particular interest is the iron-regulated hormone hepcidin and its "receptor", ferroportin, which is responsible for supplying the blood with iron. Since an excess of hepcidin is a cause of iron deficiency anemia and hepcidin deficiency leads to iron overload, the understanding of this regulatory system is the focus of our research.
1. Neves J, Leitz D, Kraut S, Brandenberger C, Agrawal R, Weissmann N, Muhlfeld C, Mall MA, Altamura S, Muckenthaler MU: Disruption of the hepcidin/ferroportin regulatory system causes pulmonary iron overload and restrictive lung disease. EBioMedicine 2017, 20:230-239
2.Mleczko-Sanecka K, da Silva AR, Call D, Neves J, Schmeer N, Damm G, Seehofer D, Muckenthaler MU: Imatinib and spironolactone suppress hepcidin expression. Haematologica 2017;102:1173-1184
3. Muckenthaler MU, Rivella S, Hentze MW, Galy B: A red carpet for iron metabolism. Cell 2017, 168:344-361
4. Vinchi F, Costa da Silva M, Ingoglia G, Petrillo S, Brinkman N, Zuercher A, Cerwenka A, Tolosano E, Muckenthaler MU: Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease. Blood. 2016, 28;127(4):473-86.
5. Guida C, Altamura S, Klein FA, Galy B, Boutros M, Ulmer AJ, Hentze MW, Muckenthaler MU: A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia. Blood 2015; 125(14):2265-75
6.ltamura S, Kessler R, Gröne HJ, Gretz N, Hentze MW, Galy B, Muckenthaler MU: Resistance of Ferroportin to Hepcidin Binding causes Exocrine Pancreatic Failure and Fatal Iron Overload. Cell Metab. 2014; 20(2):359-67