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Molecular Medicine Partnership Unit

The MMPU is a joint venture between the Medical Faculty of the University of Heidelberg and the European Molecular Biology Laboratory (EMBL).

Iron Homeostasis

Matthias W. Hentze and Martina Muckenthaler

Our research interest

As an essential nutrient and a potential toxin, iron poses an exquisite regulatory problem in biology and medicine. Disturbances of the delicate balancing systems for systemic and/or local iron homeostasis are emerging as underlying causes of common hematological, metabolic and neurodegenerative diseases.

Our research aims to understand the physiological control of cellular and systemic iron metabolism and its disturbances in human disease

Background

Iron is essential for fundamental metabolic processes in cells and organisms. Regulation of systemic iron homeostasis evolved to maintain a plasma iron concentration that secures adequate supplies while preventing organ iron overload.

The homeostatic system must react to signals from pathways that consume iron (e.g. the erythropoiesis) and send signals to cells that supply iron (e.g. duodenal enterocytes, which absorb iron from the diet; macrophages which recycle iron from senescent erythrocytes, and hepatocytes which are the major iron stores). The small hepatic peptide hormone hepcidin (Hamp, LEAP1) orchestrates these iron fluxes and controls the amount of available extracellular iron by interacting with the iron exporter ferroportin: binding of hepcidin induces ferroportin internalization and degradation, thus reducing the levels of iron in circulation.

Goals

Our work is based on modern “omics” analyses of cultured cells, animal models (mostly mouse) and clinical samples. Hypotheses generated in this way are then pursued for a more detailed understanding of regulatory mechanisms involved in iron homeostasis and the identification of novel regulators of iron metabolism. We then aim to translate new results into understanding human disease and to contribute to clinical patient management.

Specifically, our current and future work will focus on four themes:

  • The hepcidin/ferroportin regulatory system.
  • The role of iron in atherosclerosis.
  • Iron management in the central nervous system.
  • Iron in the tumor microenvironment.

Podcast
Members of our group participate in a new podcast series published weekly by Blood.
Blood Podcast on Apple Podcasts
Blood Podcast | Podcast on Spotify

Interdisciplinary science exhibition on the history and present of bloodletting
See here for more information.

Selected publications

Alterations of iron homeostasis as a potential druggable driver of long COVID.
Marques O, Muckenthaler MU.
Nat Immunol. 2024 Mar;25(3):387-389. doi: 10.1038/s41590-024-01759-3.PMID: 38429459

Iron homeostasis in mice: does liver lobe matter?
Colucci S, Carvalho Oliveira T, Muckenthaler MU, Marques O.
Am J Physiol Gastrointest Liver Physiol. 2023 Nov 1;325(5):G453-G457. doi: 10.1152/ajpgi.00085.2023. Epub 2023 Sep 5.PMID: 37667844

Mechanisms of controlling iron homeostasis.
Galy, B. Conrad, M., and Muckenthaler MU.
Nature Reviews in Cell and Molecular Biology (2023)

FKBP12 inhibits hepcidin expression by modulating BMP receptors interaction and ligand responsiveness in hepatocytes.
Pettinato M, Dulja A, Colucci S, Furiosi V, Fette F, Steinbicker AU, Muckenthaler MU, Nai A, Pagani A, Silvestri L.
Am J Hematol. 2023 Aug;98(8):1223-1235. doi: 10.1002/ajh.26961. Epub 2023 May 18.PMID: 37199280

Association Between Ferritin Levels and Altitude-Dependent Cardiorespiratory Fitness in Mountain Guides.
Pühringer R, Muckenthaler M, Burtscher M.
High Alt Med Biol. 2023 Jun;24(2):139-143. doi: 10.1089/ham.2023.0016. Epub 2023 May 3.PMID: 37134197

Repression of the iron exporter ferroportin may contribute to hepatocyte iron overload in individuals with type 2 diabetes.
Qiu R, Alikhanyan K, Volk N, Marques O, Mertens C, Agarvas AR, Singh S, Pepperkok R, Altamura S, Muckenthaler MU.
Mol Metab. 2022 Dec;66:101644. doi: 10.1016/j.molmet.2022.101644. Epub 2022 Nov 24.PMID: 36436807

The role of iron in chronic inflammatory diseases – from mechanisms to treatment options in Anemia of Inflammation.
Marques O, Weiss G, Muckenthaler MU.
Blood. 2022 Aug 22:blood.2021013472. doi: 10.1182/blood.2021013472. PMID: 35994752

Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction.
Muckenthaler L, Marques O, Colucci S, Kunz J, Fabrowski P, Bast T, Altamura S, Höchsmann B, Schrezenmeier H, Langlotz M, Richter-Pechanska P, Rausch T, Hofmeister-Mielke N, Gunkel N, Hentze MW, Kulozik AE, Muckenthaler MU.
Blood. 2022 Mar 3;139(9):1418-1422. doi: 10.1182/blood.2021013519. PMID: 34875027

The Macrophage Iron Signature in Health and Disease
Christina Mertens, Oriana Marques, Natalie K. Horvat, Manuela Simonetti, Martina U. Muckenthaler and Michaela Jung
Int. J. Mol. Sci.2021, 22(16), 8457

20 years of Hepcidin: How far we have come.
Colucci S, Marques O, Altamura S.
Semin Hematol. 2021 Jul;58(3):132-144. doi: 10.1053/j.seminhematol.2021.05.001. Epub 2021 Jun 12. PMID: 34389105

Core Cross-Linked Polymeric Micelles for Specific Iron Delivery: Inducing Sterile Inflammation in Macrophages.
Bauer TA, Horvat NK, Marques O, Chocarro S, Mertens C, Colucci S, Schmitt S, Carrella LM, Morsbach S, Koynov K, Fenaroli F, Blümler P, Jung M, Sotillo R, Hentze MW, Muckenthaler MU, Barz M.
Adv Healthc Mater. 2021 Jun 16:e2100385. doi: 10.1002/adhm.202100385. Online ahead of print. PMID: 34137217

Liver Sinusoidal Endothelial Cells Suppress Bone Morphogenetic Protein 2 Production in Response to TGFβ Pathway Activation.
Colucci S, Altamura S, Marques O, Dropmann A, Horvat NK, Müdder K, Hammad S, Dooley S, Muckenthaler MU.
Hepatology. 2021 May 13. doi: 10.1002/hep.31900. Online ahead of print. PMID: 33982327

The role of cellular iron deficiency in controlling iron export.
Link C, Knopf JD, Marques O, Lemberg MK, Muckenthaler MU.
Biochim Biophys Acta Gen Subj. 2021 Mar;1865(3):129829. doi: 10.1016/j.bbagen.2020.129829. Epub 2020 Dec 16. PMID: 33340587

Vasculo-toxic and pro-inflammatory action of unbound haemoglobin, haem and iron in transfusion-dependent patients with haemolytic anaemias.
Vinchi F, Sparla R, Passos ST, Sharma R, Vance SZ, Zreid HS, Juaidi H, Manwani D, Yazdanbakhsh K, Nandi V, Silva AMN, Agarvas AR, Fibach E, Belcher JD, Vercellotti GM, Ghoti H, Muckenthaler MU.
Br J Haematol. 2021 Mar 15. doi: 10.1111/bjh.17361. Online ahead of print. PMID: 33723861

Mild Attenuation of the Pulmonary Inflammatory Response in a Mouse Model of Hereditary Hemochromatosis Type 4.
Marques O, Neves J, Horvat NK, Altamura S, Muckenthaler MU.
Front Physiol. 2021 Jan 13;11:589351. doi: 10.3389/fphys.2020.589351. eCollection 2020. PMID: 33519502

Global analysis of RNA-binding protein dynamics by comparative and enhanced RNA interactome capture.
Perez-Perri JI, Noerenberg M, Kamel W, Lenz CE, Mohammed S, Hentze MW, Castello A.
Nat Protoc. 2021 Jan;16(1):27-60. doi: 10.1038/s41596-020-00404-1. Epub 2020 Nov 18.
PMID: 33208978

Iron deficiency.
Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW.
Lancet. 2021 Jan 16;397(10270):233-248. doi: 10.1016/S0140-6736(20)32594-0. Epub 2020 Dec 4. PMID: 33285139 Review.

Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies.
Cortese M, Lee JY, Cerikan B, Neufeldt CJ, Oorschot VMJ, Köhrer S, Hennies J, Schieber NL, Ronchi P, Mizzon G, Romero-Brey I, Santarella-Mellwig R, Schorb M, Boermel M, Mocaer K, Beckwith MS, Templin RM, Gross V, Pape C, Tischer C, Frankish J, Horvat NK, Laketa V, Stanifer M, Boulant S, Ruggieri A, Chatel-Chaix L, Schwab Y, Bartenschlager R.
Cell Host Microbe. 2020 Dec 9;28(6):853-866.e5. doi: 10.1016/j.chom.2020.11.003. Epub 2020 Nov 17. PMID: 33245857

HFE and ALK3 act in the same signaling pathway.
Traeger L, Schnittker J, Dogan DY, Oguama D, Kuhlmann T, Muckenthaler MU, Krijt J, Urzica EI, Steinbicker AU.
Free Radic Biol Med. 2020 Nov 20;160:501-505. doi: 10.1016/j.freeradbiomed.2020.08.023. Epub 2020 Aug 27. PMID: 32861780

Chromatin accessibility landscape of pediatric T-lymphoblastic leukemia and human T-cell precursors.
Erarslan-Uysal B, Kunz JB, Rausch T, Richter-Pechańska P, van Belzen IA, Frismantas V, Bornhauser B, Ordoñez-Rueada D, Paulsen M, Benes V, Stanulla M, Schrappe M, Cario G, Escherich G, Bakharevich K, Kirschner-Schwabe R, Eckert C, Loukanov T, Gorenflo M, Waszak SM, Bourquin JP, Muckenthaler MU, Korbel JO, Kulozik AE.
EMBO Mol Med. 2020 Sep 7;12(9):e12104. doi: 10.15252/emmm.202012104. Epub 2020 Aug 5. PMID: 32755029

Regulation of iron homeostasis: Lessons from mouse models.
Altamura S, Marques O, Colucci S, Mertens C, Alikhanyan K, Muckenthaler MU.
Mol Aspects Med. 2020 Aug 10:100872. doi: 10.1016/j.mam.2020.100872. Online ahead of print. PMID: 32792212

Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction.
Vinchi F, Porto G, Simmelbauer A, Altamura S, Passos ST, Garbowski M, Silva AMN, Spaich S, Seide SE, Sparla R, Hentze MW, Muckenthaler MU.
Eur Heart J. 2020 Jul 21;41(28):2681-2695. doi: 10.1093/eurheartj/ehz112. PMID: 30903157

Glutathione peroxidase 4 and vitamin E control reticulocyte maturation, stress erythropoiesis and iron homeostasis.
Altamura S, Vegi NM, Hoppe PS, Schroeder T, Aichler M, Walch A, Okreglicka K, Hültner L, Schneider M, Ladinig C, Kuklik-Roos C, Mysliwietz J, Janik D, Neff F, Rathkolb B, de Angelis MTH, Buske C, Silva ARD, Muedder K, Conrad M, Ganz T, Kopf M, Muckenthaler MU, Bornkamm GW.
Haematologica. 2020 Apr;105(4):937-950. doi: 10.3324/haematol.2018.212977. Epub 2019 Jun 27. PMID: 31248967

Iron-Related Parameters are Altered Between C57BL/6N and C57BL/6J Mus Musculus Wild-Type Substrains.
Marques O, Neves J, Horvat NK, Colucci S, Guida C, Muckenthaler MU.
Hemasphere. 2019 Oct 22;3(6):e304. doi: 10.1097/HS9.0000000000000304. eCollection 2019 Dec. PMID: 31976478

SLN124, a GalNAc-siRNA Conjugate Targeting TMPRSS6, Efficiently Prevents Iron Overload in Hereditary Haemochromatosis Type 1.
Altamura S, Schaeper U, Dames S, Löffler K, Eisermann M, Frauendorf C, Müdder K, Neves J, Muckenthaler MU.
Hemasphere. 2019 Oct 1;3(6):e301. doi: 10.1097/HS9.0000000000000301. eCollection 2019 Dec. PMID: 31976476

Iron accumulation in tumor-associated macrophages marks an improved overall survival in patients with lung adenocarcinoma.
Thielmann CM, Costa da Silva M, Muley T, Meister M, Herpel E, Muckenthaler MU.
Sci Rep. 2019 Aug 5;9(1):11326. doi: 10.1038/s41598-019-47833-x. PMID:31383898

The increase in hemoglobin concentration with altitude varies among human populations.
Gassmann M, Mairbäurl H, Livshits L, Seide S, Hackbusch M, Malczyk M, Kraut S, Gassmann NN, Weissmann N, Muckenthaler MU.
Ann N Y Acad Sci. 2019 Aug;1450(1):204-220. doi: 10.1111/nyas.14136. Epub 2019 Jun 30. PMID: 31257609

miR-148a regulates expression of the transferrin receptor 1 in hepatocellular carcinoma.
Babu KR, Muckenthaler MU.
Sci Rep. 2019 Feb 6;9(1):1518. doi: 10.1038/s41598-018-35947-7. PMID:30728365

Iron Homeostasis in the Lungs-A Balance between Health and Disease.
Neves J, Haider T, Gassmann M, Muckenthaler MU.
Pharmaceuticals (Basel). 2019 Jan 1;12(1). pii: E5. doi: 10.3390/ph12010005. Review. PMID:30609678

PDX models recapitulate the genetic and epigenetic landscape of pediatric T-cell leukemia.
Richter-Pechańska P, Kunz JB, Bornhauser B, von Knebel Doeberitz C, Rausch T, Erarslan-Uysal B, Assenov Y, Frismantas V, Marovca B, Waszak SM, Zimmermann M, Seemann J, Happich M, Stanulla M, Schrappe M, Cario G, Escherich G, Bakharevich K, Kirschner-Schwabe R, Eckert C, Muckenthaler MU, Korbel JO, Bourquin JP, Kulozik AE.
EMBO Mol Med. 2018 Dec;10(12). pii: e9443. doi: 10.15252/emmm.201809443. PMID:30389682

Transferrin receptor 2 is a potential novel therapeutic target for β-thalassemia: evidence from a murine model.
Artuso I, Lidonnici MR, Altamura S, Mandelli G, Pettinato M, Muckenthaler MU, Silvestri L, Ferrari G, Camaschella C, Nai A.
Blood. 2018 Nov 22;132(21):2286-2297. doi: 10.1182/blood-2018-05-852277. Epub 2018 Sep 12.PMID:30209118

ALK3 undergoes ligand-independent homodimerization and BMP-induced heterodimerization with ALK2.
Traeger L, Gallitz I, Sekhri R, Bäumer N, Kuhlmann T, Kemming C, Holtkamp M, Müller JC, Karst U, Canonne-Hergaux F, Muckenthaler MU, Bloch DB, Olschewski A, Bartnikas TB, Steinbicker AU.
Free Radic Biol Med. 2018 Sep 15;129:127-137. doi: 10.1016/j.freeradbiomed.2018.09.021. [Epub ahead of print] PMID:30227271

Dietary stearic acid regulates mitochondria in vivo in humans.
Senyilmaz-Tiebe D, Pfaff DH, Virtue S, Schwarz KV, Fleming T, Altamura S, Muckenthaler MU, Okun JG, Vidal-Puig A, Nawroth P, Teleman AA.
Nat Commun. 2018 Aug 7;9(1):3129. doi: 10.1038/s41467-018-05614-6.PMID:30087348

MAP3K7 is recurrently deleted in pediatric T-lymphoblastic leukemia and affects cell proliferation independently of NF-κB. Cordas Dos Santos DM, Eilers J, Sosa Vizcaino A, Orlova E, Zimmermann M, Stanulla M, Schrappe M, Börner K, Grimm D, Muckenthaler MU, Kulozik AE, Kunz JB.
BMC Cancer. 2018 Jun 18;18(1):663. doi: 10.1186/s12885-018-4525-0. PMID: 29914415

The hepcidin-ferroportin axis controls the iron content of Salmonella-containing vacuoles in macrophages.
Lim D, Kim KS, Jeong JH, Marques O, Kim HJ, Song M, Lee TH, Kim JI, Choi HS, Min JJ, Bumann D, Muckenthaler MU, Choy HE.
Nat Commun. 2018 May 29;9(1):2091. doi: 10.1038/s41467-018-04446-8. PMID: 29844422

Hepatic Smad7 overexpression causes severe iron overload in mice.
Lai D, Teng F, Hammad S, Werle J, Maas T, Teufel A, Muckenthaler MU, Dooley S, Vujić Spasić M.
Blood. 2018 Feb 1;131(5):581-585. doi: 10.1182/blood-2017-07-796797. Epub 2017 Dec 13. No
bstract available. PMID:29237592

Uncoupled iron homeostasis in type 2 diabetes mellitus.
Altamura S, Kopf S, Schmidt J, Müdder K, da Silva AR, Nawroth P, Muckenthaler MU.
J Mol Med (Berl). 2017 Dec;95(12):1387-1398. doi: 10.1007/s00109-017-1596-3. Epub 2017 Oct 3.PMID: 28971221

Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages.
Costa da Silva M, Breckwoldt MO, Vinchi F, Correia MP, Stojanovic A, Thielmann CM, Meister M, Muley T, Warth A, Platten M, Hentze MW, Cerwenka A, Muckenthaler MU.
Front Immunol. 2017 Nov 8;8:1479. doi: 10.3389/fimmu.2017.01479. eCollection 2017. PMID: 29167669

Hepcidin is regulated by promoter-associated histone acetylation and HDAC3.
Pasricha SR, Lim PJ, Duarte TL, Casu C, Oosterhuis D, Mleczko-Sanecka K, Suciu M, Da Silva AR, Al-Hourani K, Arezes J, McHugh K, Gooding S, Frost JN, Wray K, Santos A, Porto G, Repapi E, Gray N, Draper SJ, Ashley N, Soilleux E, Olinga P, Muckenthaler MU, Hughes JR, Rivella S, Milne TA, Armitage AE, Drakesmith H.
Nat Commun. 2017 Sep 1;8(1):403. doi: 10.1038/s41467-017-00500-z.PMID: 28864822

Low-iron diet and chelation therapy rescue severe atherosclerosis associated with high circulating iron levels
Francesca Vinchi, Richard Sparla, Andreas Simmelbauer, Sandro Altamura, Sebastian Speich, Bruno Galy, Matthias W. Hentze, Martina U. Muckenthaler
Atherosclerosis, Volume 263, August 2017, Pages e15-e16

Elevated systemic heme and iron levels as risk factor for vascular dysfunction and atherosclerosis: Evidence from a beta-thalassemia cohort study
Francesca Vinchi, Gregory M. Vercellotti, John D. Belcher, Richard Sparla, Eitan Fibach, Hala Zreid, Rushdy Rasras, Hussam Ghoti, Martina U. Muckenthaler, Eliezer A. Rachmilewitz
Atherosclerosis, August 2017, Volume 263, Pages e107–e108

No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells.
Steinkellner H, Singh HN, Muckenthaler MU, Goldenberg H, Moganty RR, Scheiber-Mojdehkar B, Sturm B.
Gene. 2017 Jul 20;621:5-11. doi: 10.1016/j.gene.2017.04.014. Epub 2017 Apr 12. PMID: 28412459

NOTCH1 mutation, TP53 alteration and myeloid antigen expression predict outcome heterogeneity in children with first relapse of T-cell acute lymphoblastic leukemia.
Hof J, Kox C, Groeneveld-Krentz S, Bandapalli OR, Karawajew L, Schedel K, Kunz JB, Eckert C, Ludwig WD, Ratei R, Rhein P, Henze G, Muckenthaler MU, Kulozik AE, von Stackelberg A, Kirschner-Schwabe R.
Haematologica. 2017 Jul;102(7):e249-e252. doi: 10.3324/haematol.2016.157792. Epub 2017 Mar 30.PMID:28360149

Imatinib and spironolactone suppress hepcidin expression.
Mleczko-Sanecka K, da Silva AR, Call D, Neves J, Schmeer N, Damm G, Seehofer D, Muckenthaler MU.
Haematologica. 2017 Jul;102(7):1173-1184. doi: 10.3324/haematol.2016.162917. Epub 2017 Apr 6.PMID:28385785

Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis.
Metzendorf C, Zeigerer A, Seifert S, Sparla R, Najafi B, Canonne-Hergaux F, Zerial M, Muckenthaler MU.
Sci Rep. 2017 Jun 22;7(1):4023. doi: 10.1038/s41598-017-02898-4.PMID:28642463

Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease.
Neves J, Leitz D, Kraut S, Brandenberger C, Agrawal R, Weissmann N, Mühlfeld C, Mall MA, Altamura S, Muckenthaler MU.
EBioMedicine. 2017 Jun;20:230-239. doi: 10.1016/j.ebiom.2017.04.036. Epub 2017 Apr 29.PMID:28499927

Cellular citrate levels establish a regulatory link between energy metabolism and the hepatic iron hormone hepcidin.
da Silva AR, Neves J, Mleczko-Sanecka K, Tandon A, Sauer SW, Hentze MW, Muckenthaler MU.
J Mol Med (Berl). 2017 Jun 5. doi: 10.1007/s00109-017-1551-3. PMID: 28585096

Cdk6 contributes to cytoskeletal stability in erythroid cells.
Uras IZ, Scheicher RM, Kollmann K, Glösmann M, Prchal-Murphy M, Tigan AS, Fux DA, Altamura S, Neves J, Muckenthaler MU, Bennett KL, Kubicek S, Hinds PW, von Lindern M, Sexl V.
Haematologica. 2017 Jun;102(6):995-1005. doi: 10.3324/haematol.2016.159947. Epub 2017 Mar 2.PMID:28255017

Dicarbonyls and Advanced Glycation End-Products in the Development of Diabetic Complications and Targets for Intervention.
Brings S, Fleming T, Freichel M, Muckenthaler MU, Herzig S, Nawroth PP.
Int J Mol Sci. 2017 May 5;18(5). pii: E984. doi: 10.3390/ijms18050984. Review.PMID:28475116

Pathophysiological consequences and benefits of HFE mutations: 20 years of research.
Hollerer I, Bachmann A, Muckenthaler MU.
Haematologica. 2017 May;102(5):809-817. doi: 10.3324/haematol.2016.160432. Epub 2017 Mar 9. Review.PMID:28280078

Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes – What We Know so Far and the Missing Links.
Groener JB, Oikonomou D, Cheko R, Kender Z, Zemva J, Kihm L, Muckenthaler M, Peters V, Fleming T, Kopf S, Nawroth PP.
Exp Clin Endocrinol Diabetes. 2017 Apr 13. doi: 10.1055/s-0043-106443.PMID:28407670

Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemia.
Richter-Pechańska P, Kunz JB, Hof J, Zimmermann M, Rausch T, Bandapalli OR, Orlova E, Scapinello G, Sagi JC, Stanulla M, Schrappe M, Cario G, Kirschner-Schwabe R, Eckert C, Benes V, Korbel JO, Muckenthaler MU, Kulozik AE.
Blood Cancer J. 2017 Feb 3;7(2):e523. doi: 10.1038/bcj.2017.3.
PMID: 28157215

A Red Carpet for Iron Metabolism.
Muckenthaler MU, Rivella S, Hentze MW, Galy B.
Cell. 2017 Jan 26;168(3):344-361. doi: 10.1016/j.cell.2016.12.034. Review. PMID: 28129536

Modelling Systemic Iron Regulation during Dietary Iron Overload and Acute Inflammation: Role of Hepcidin-Independent Mechanisms.
Enculescu M, Metzendorf C, Sparla R, Hahnel M, Bode J, Muckenthaler MU, Legewie S.
PLoS Comput Biol. 2017 Jan 9;13(1):e1005322. doi: 10.1371/journal.pcbi.1005322.
PMID: 28068331

Important publications 2016 and earlier

In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis.
Kirschbaum K, Sonner JK, Zeller MW, Deumelandt K, Bode J, Sharma R, Krüwel T, Fischer M, Hoffmann A, Costa da Silva M, Muckenthaler MU, Wick W, Tews B, Chen JW, Heiland S, Bendszus M, Platten M, Breckwoldt MO.
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13227-13232.
PMID: 27799546

Orphan nuclear receptor SHP regulates iron metabolism through inhibition of BMP6-mediated hepcidin expression.
Kim DK, Kim YH, Jung YS, Kim KS, Jeong JH, Lee YS, Yuk JM, Oh BC, Choy HE, Dooley S, Muckenthaler MU, Lee CH, Choi HS.
Sci Rep. 2016 Sep 30;6:34630. doi: 10.1038/srep34630.
PMID: 27688041

CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia.
Palmi C, Savino AM, Silvestri D, Bronzini I, Cario G, Paganin M, Buldini B, Galbiati M, Muckenthaler MU, Bugarin C, Mina PD, Nagel S, Barisone E, Casale F, Locatelli F, Nigro LL, Micalizzi C, Parasole R, Pession A, Putti MC, Santoro N, Testi AM, Ziino O, Kulozik AE, Zimmermann M, Schrappe M, Villa A, Gaipa G, Basso G, Biondi A, Valsecchi MG, Stanulla M, Conter V, Kronnie GT, Cazzaniga G.
Oncotarget. 2016 Jul 15. doi: 10.18632/oncotarget.10610.

Transforming Growth Factor β1 (TGF-β1) Activates Hepcidin mRNA Expression in Hepatocytes.
Chen S, Feng T, Vujić Spasić M, Altamura S, Breitkopf-Heinlein K, Altenöder J, Weiss TS, Dooley S, Muckenthaler MU.
J Biol Chem. 2016 Jun 17;291(25):13160-74. doi: 10.1074/jbc.M115.691543. Epub 2016 Apr 27.

miR-20a regulates expression of the iron exporter ferroportin in lung cancer.
Babu KR, Muckenthaler MU.
J Mol Med (Berl). 2016 Mar;94(3):347-59. doi: 10.1007/s00109-015-1362-3. Epub 2015 Nov 12

Mice with hepcidin-resistant ferroportin accumulate iron in the retina.
Theurl M, Song D, Clark E, Sterling J, Grieco S, Altamura S, Galy B, Hentze M, Muckenthaler MU, Dunaief JL.
FASEB J. 2016 Feb;30(2):813-23. doi: 10.1096/fj.15-276758. Epub 2015 Oct 27. PMID: 26506980

Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease.
Vinchi F, Costa da Silva M, Ingoglia G, Petrillo S, Brinkman N, Zuercher A, Cerwenka A, Tolosano E, Muckenthaler MU.
Blood. 2016 Jan 28;127(4):473-86. doi: 10.1182/blood-2015-08-663245. Epub 2015 Dec 16.

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation.
Jaekel N, Lieder K, Albrecht S, Leismann O, Hubert K, Bug G, Kröger N, Platzbecker U, Stadler M, de Haas K, Altamura S, Muckenthaler MU, Niederwieser D, Al-Ali HK.
Bone Marrow Transplant. 2016 Jan;51(1):89-95. doi: 10.1038/bmt.2015.204. Epub 2015 Sep 14.

Pediatric T-lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation.
Kunz JB, Rausch T, Bandapalli OR, Eilers J, Pechanska P, Schuessele S, Assenov Y, Stütz AM, Kirschner-Schwabe R, Hof J, Eckert C, von Stackelberg A, Schrappe M, Stanulla M, Koehler R, Avigad S, Elitzur S, Handgretinger R, Benes V, Weischenfeldt J, Korbel JO, Muckenthaler MU, Kulozik AE.
Haematologica. 2015 Aug 20. pii: haematol.2015.129692. PMID: 26294725

Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection.Nairz M, Ferring-Appel D, Casarrubea D, Sonnweber T, Viatte L, Schroll A, Haschka D, Fang FC, Hentze MW, Weiss G, Galy B.
Cell Host Microbe. 2015 Aug 12;18(2):254-61. doi: 10.1016/j.chom.2015.06.017. Epub 2015 Jul 16. PMID: 26190773

Elevated hepcidin serum level in response to inflammatory and iron signals in exercising athletes is independent of moderate supplementation with vitamin C and E.
Díaz V, Peinado AB, Barba-Moreno L, Altamura S, Butragueño J, González-Gross M, Alteheld B, Stehle P, Zapico AG, Muckenthaler MU, Gassmann M.
Physiol Rep. 2015 Aug;3(8). pii: e12475. doi: 10.14814/phy2.12475. PMID: 26243212

Adaptation of iron requirement to hypoxic conditions at high altitude.
Gassmann M, Muckenthaler MU.
J Appl Physiol (1985). 2015 Jul 16:jap.00248.2015. doi: 10.1152/japplphysiol.00248.2015. [Epub ahead of print] PMID: 26183475

Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo.
Costa M, Cruz E, Oliveira S, Benes V, Ivacevic T, Silva MJ, Vieira I, Dias F, Fonseca S, Gonçalves M, Lima M, Leitão C, Muckenthaler MU, Pinto J, Porto G.
PLoS One. 2015 Apr 16;10(4):e0124246. doi: 10.1371/journal.pone.0124246. eCollection 2015. PMID: 25880808

A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia.
Guida C, Altamura S, Klein FA, Galy B, Boutros M, Ulmer AJ, Hentze MW, Muckenthaler MU.
Blood. 2015 Apr 2;125(14):2265-75. doi: 10.1182/blood-2014-08-595256. Epub 2015 Feb 6.
PMID:25662334

Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome.
Lenzhofer M, Schroedl F, Trost A, Kaser-Eichberger A, Wiedemann H, Strohmaier C, Hohensinn M, Strasser M, Muckenthaler MU Grabner G, Aigner E, Reitsamer HA.
Optom Vis Sci. 2015 Apr;92(4 Suppl 1):S40-7. doi: 10.1097/OPX.0000000000000544. PMID:25756341

Iron regulatory protein 1 sustains mitochondrial iron loading and function in frataxin deficiency.
Martelli A, Schmucker S, Reutenauer L, Mathieu JR, Peyssonnaux C, Karim Z, Puy H, Galy B, Hentze MW, Puccio H.
Cell Metab. 2015 Feb 3;21(2):311-22. doi: 10.1016/j.cmet.2015.01.010.
PMID:25651183

How mutant HFE causes hereditary hemochromatosis.
Muckenthaler MU.
Blood. 2014 Aug 21;124(8):1212-3. doi: 10.1182/blood-2014-07-581744. PMID:25147378

Resistance of Ferroportin to Hepcidin Binding causes Exocrine Pancreatic Failure and Fatal Iron Overload.
Altamura S, Kessler R, Gröne HJ, Gretz N, Hentze MW, Galy B, Muckenthaler MU.
Cell Metab. 2014 Aug 5;20(2):359-67. doi: 10.1016

Novel activating mutations lacking cysteine in type I cytokine receptors in acute lymphoblastic leukemia.
Shochat C1, Tal N, Gryshkova V, Birger Y, Bandapalli OR, Cazzaniga G, Gershman N, Kulozik AE, Biondi A, Mansour MR, Twizere JC, Muckenthaler MU, Ben-Tal N, Constantinescu SN, Bercovich D, Izraeli S.
Blood. 2014 Jul 3;124(1):106-10

Atherogenesis and iron: from epidemiology to cellular level.
Vinchi F, Muckenthaler MU, Da Silva MC, Balla G, Balla J, Jeney V.
Front Pharmacol. 2014 May 5;5:94. doi: 10.3389/fphar.2014.00094. eCollection 2014. Review.

Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria
Chung J, Anderson SA, Gwynn B, Deck KM, Chen MJ, Langer NB, Shaw GC, Huston NC, Boyer LF, Datta S, Paradkar PN, Li L, Wei Z, Lambert AJ, Sahr K, Wittig JG, Chen W, Lu W, Galy B, Schlaeger TM, Hentze MW, Ward DM, Kaplan J, Eisenstein RS, Peters LL, Paw BH.
J Biol Chem. 2014 Mar 14;289(11):7835-43. doi: 10.1074/jbc.M114.547778. Epub 2014 Feb 7. Erratum in: J Biol Chem. 2014 May 16;289(20):13707. PMID:24509859

Unbiased RNAi screen for hepcidin regulators links hepcidin suppression to the proliferative Ras/RAF and the nutrient-dependent mTOR signaling pathways.
Mleczko-Sanecka, K., F. Roche, A.R. da Silva, D. Call, F. D’Allesio, A. Ragab, P.E. Lapinski, R. Ummanni, U. Korf, C. Oakes, G. Damm, L.A. D’Alessandro, U. Klingmüller, P.D. King, M. Boutros, M.W. Hentze and M.U. Muckenthaler. 
Blood. 2014 Mar 6;123(10):1574-85. doi: 10.1182/blood-2013-07-515957. Epub 2014 Jan 2.

Comparison of different IRT-PAP protocols to screen newborns for cystic fibrosis in three central European populations.
Sommerburg O, Krulisova V, Hammermann J, Lindner M, Stahl M, Muckenthaler M, Kohlmueller D, Happich M, Kulozik AE, Votava F, Balascakova M, Skalicka V, Stopsack M, Gahr M, Macek M Jr, Mall MA, Hoffmann GF.
J Cyst Fibros. 2014 Jan;13(1):15-23. doi: 10.1016/j.jcf.2013.06.003. Epub 2013 Jul 25.  

A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.
Casanovas G, Banerji A, d’Alessio F, Muckenthaler MU, Legewie S.
PLoS Comput Biol. 2014 Jan;10(1):e1003421. doi: 10.1371/journal.pcbi.1003421. Epub 2014 Jan 2.

The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse.
Bandapalli OR, Schuessele S, Kunz JB, Rausch T, Stütz AM, Tal N, Geron I, Gershman N, Izraeli S, Eilers J, Vaezipour N, Kirschner-Schwabe R, Hof J, von Stackelberg A, Schrappe M, Stanulla M, Zimmermann M, Koehler R, Avigad S, Handgretinger R, Frismantas V, Bourquin JP, Bornhauser B, Korbel JO, Muckenthaler MU, Kulozik AE.
Haematologica. 2014 Jun 27. pii: haematol.2014.104992.

High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol.
Cario G1, Rhein P, Mitlöhner R, Zimmermann M, Bandapalli OR, Romey R, Moericke A, Ludwig WD, Ratei R, Muckenthaler MU, Kulozik AE, Schrappe M, Stanulla M, Karawajew L.
Haematologica. 2014 Jan;99(1):103-10. doi: 10.3324/haematol.2013.090225. Epub 2013 Aug 2.

Pathologies at the nexus of blood coagulation and inflammation: thrombin in hemostasis, cancer and beyond.
Danckwardt, S., M.W. Hentze and A.E. Kulozik. 
J Mol Med (Berl). 2013 Nov;91(11):1257-71. doi: 10.1007/s00109-013-1074-5. Epub 2013 Aug 17.

The RNA-binding protein repertoire of embryonic stem cells.
Kwon, S.C., H. Yi, K. Eichelbaum, S. Föhr, B. Fischer, K.T. You, A. Castello, J. Krijgsveld, M.W. Hentze and V.N. Kim. 
Nature Struc. Mol Biol. 2013 Sep;20(9):1122-30. doi: 10.1038/nsmb.2638. Epub 2013 Aug 4.

Computerized image analysis of iron-stained macrophages.
Benesova K, Schaefer SM, Mall MA, Muckenthaler MU
Ann Hematol 2013 Sep;92(9):1195-9. doi: 10.1007/s00277-013-1740-2. Epub 2013 Apr 17

Mycn and hdac2 cooperate to repress mir-183 signaling in neuroblastoma
Lodrini M, Oehme I, Schroeder C, Milde T, Schier MC, Kopp-Schneider A, Schulte JH, Fischer M, De Preter K, Pattyn F, Castoldi M, Muckenthaler MU, Kulozik AE, Westermann F, Witt O, Deubzer HE
Nucleic Acids Res 2013 Jul; 41:6018-6033

Notch1 activation clinically antagonizes the unfavorable effect of pten inactivation in bfm-treated children with precursor t-cell acute lymphoblastic leukemia.
Bandapalli OR, Zimmermann M, Kox C, Stanulla M, Schrappe M, Ludwig WD, Koehler R, Muckenthaler MU, Kulozik AE
Haematologica 2013 Jun;98:928-936

Iron refractory iron deficiency anemia.
De Falco L, Sanchez M, Silvestri L, Kannengiesser C, Muckenthaler MU, Iolascon A, Gouya L, Camaschella C, Beaumont C
Haematologica 2013 Jun;98:845-853

Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in salmonella infection.
Nairz M, Schleicher U, Schroll A, Sonnweber T, Theurl I, Ludwiczek S, Talasz H, Brandacher G, Moser PL, Muckenthaler MU, Fang FC, Bogdan C, Weiss G
J Exp Med. 2013 May 6;210(5):855-73. doi: 10.1084/jem.20121946. Epub 2013 Apr 29

Iron regulatory proteins control a mucosal block to intestinal iron absorption.
Galy, B., D. Ferring-Appel, C. Becker, N. Gretz, H.-J. Gröne, K. Schümann and M.W. Hentze. 
Cell Rep. 2013 Mar 28;3(3):844-57. doi: 10.1016/j.celrep.2013.02.026. Epub 2013 Mar 21.

The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice
Casanovas G, Spasic MV, Casu C, Rivella S, Strelau J, Unsicker K, Muckenthaler MU
Haematologica. 2013 Mar;98(3):444-7. doi: 10.3324/haematol.2012.069807. Epub 2012 Sep 14

Novel mutations in the ferritin-l iron-responsive element that only mildly impair irp binding cause hereditary hyperferritinaemia cataract syndrome.
Luscieti S, Tolle G, Aranda J, Campos CB, Risse F, Moran E, Muckenthaler MU, Sanchez M
Orphanet J Rare Dis 2013 Feb 19;8:30

Smad6 and smad7 are co-regulated with hepcidin in mouse models of iron overload.
Vujic Spasic M, Sparla R, Mleczko-Sanecka K, Migas MC, Breitkopf-Heinlein K, Dooley S, Vaulont S, Fleming RE, Muckenthaler MU
Biochim Biophys Acta 2013 Jan;1832:76-84

Pegylated interferon-α induced hypoferremia is associated with the immediate response to treatment in hepatitis C.
Ryan JD, Altamura S, Devitt E, Mullins S, Lawless MW, Muckenthaler MU, Crowe J.
Hepatology. 2012 Aug;56(2):492-500. doi: 10.1002/hep.25666. Epub 2012 Jun 11

Hfe deficiency impairs pulmonary neutrophil recruitment in response to inflammation.
Benesova K, Vujić Spasić M, Schaefer SM, Stolte J, Baehr-Ivacevic T, Waldow K, Zhou Z, Klingmueller U, Benes V, Mall MA, Muckenthaler MU.
PLoS One. 2012;7(6):e39363. Epub 2012 Jun 21

The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation.
D’Alessio F, Hentze MW, Muckenthaler MU.
J Hepatol. 2012 Jun 21.

Regulation of iron homeostasis by microRNAs.
Castoldi M, Muckenthaler MU.
Cell Mol Life Sci. 2012 Jun 9.

Quantitative magnetic analysis reveals ferritin-like iron as the most predominant iron-containing species in the murine Hfe-haemochromatosis.
Gutiérrez L, Vujić Spasić M, Muckenthaler MU, Lázaro FJ.
Biochim Biophys Acta. 2012 Jul;1822(7):1147-53. Epub 2012 Mar 20.

Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by IRPs.
Sanchez, M., B. Galy, B. Schwanhaeusser, J. Blake, T. Bähr-Ivacevic, V. Benes, M. Selbach, M.U. Muckenthaler and M.W. Hentze.
Blood 118: e168-79, Nov 2011

Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II.
Casanovas G, Swinkels DW, Altamura S, Schwarz K, Laarakkers CM, Gross HJ, Wiesneth M, Heimpel H, Muckenthaler MU.
J Mol Med (Berl). 2011 Aug;89(8):811-6

The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice.
Castoldi M, Vujić Spasić M, Altamura S, Elmén J, Lindow M, Kiss J, Stolte J, Sparla R, D’Alessandro LA, Klingmüller U, Fleming RE, Longerich T, Gröne HJ, Benes V, Kauppinen S, Hentze MW, Muckenthaler MU.
J Clin Invest. 2011 Apr 1;121(4):1386-96

Systems analysis of iron metabolism: the network of iron pools and fluxes.
Lopes TJ, Luganskaja T, Vujić Spasić M, Hentze MW, Muckenthaler MU, Schümann K, Reich JG
BMC Syst Biol. 2010 Aug 13;4:112

Two to tango: regulation of mammalian iron metabolism.
Hentze, M.W., M.U. Muckenthaler, B. Galy and C. Camaschella
Cell 142, 24-38, 2010

The IronChip evaluation package: a package of perl modules for robust analysis of custom microarrays.
Vainshtein, Y., M. Sanchez, A. Brazma, M.W. Hentze, T. Dandekar and M.U. Muckenthaler
BMC Bioinf. 11, 112, 2010

SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression.
Mleczko-Sanecka, K., G. Casanovas, A. Ragab, K. Breitkopf, M. Boutros, S. Dooley, M.W. Hentze and M.U. Muckenthaler.
Blood 115, 2657-2665, 2010.

Bone morphogenetic protein (BMP)-responsive elements located in the proximal and distal hepcidin promoter are critical for its response to HJV/BMP/SMAD.
Casanovas G, Mleczko-Sanecka K, Altamura S, Hentze MW, Muckenthaler MU.
_J Mol Me_d. 2009 Feb; 87, 471-480

Hfe acts in hepatocytes to prevent hemochromatosis.
Maja Vujić Spasić, Judit Kiss, Thomas Herrmann, Bruno Galy, Stefanie Martinache, Jens Stolte, Hermann-Josef Gröne, Wolfgang Stremmel, Matthias W. Hentze and Martina U. Muckenthaler.
_Cell Metabolis_m 2008 Feb;7(2):173-8

Ca2+ channel blockers reverse iron overload by a novel mechanism via divalent metal transporter (DMT)-1.
Ludwiczek, S., I. Theurl, M. U. Muckenthaler, M. Jakab, S. Mair, M. Theurl, M. Paulmichl, M.W. Hentze, M. Ritter and G. Weiss.
Nature Medicine 2007 Apr;13(4):448-54

STAT-3 mediates hepatic hepcidin expression and its inflammatory stimulation.
Verga Falzacappa, M.V., Vujic Spasic, M., Hess, R., Stolte, J., Hentze, M.W. and Muckenthaler, M.U.
Blood 2007 Jan 1;109(1):353-8

Physiologic systemic iron metabolism in mice deficient for duodenal Hfe.
Vujic Spasic, M., Kiss, J., Herrmann, T., Hess, R., Stolte, J., Galy, B., Rathkolb, B., Wolf, E., Stremmel, W., Hentze, M.W. and Muckenthaler, M.U.
Blood 2007 May 15;109(10):4511-7. Epub 2007 Jan 30

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Matthias Hentze and Martina Muckenthaler
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