Babitt, Jodie, MD

Phone: 617-726-0429
Lab: Babitt, Jodie


My laboratory is focused on elucidating the molecular and cellular mechanisms involved in iron homeostasis. Our ultimate goal is to identify new treatment strategies for disorders of iron homeostasis, such as the anemia of chronic disease and the iron overload disorder hemochromatosis.

Based on its ability to donate and accept electrons, iron is essential for many biological reactions important for living organisms including oxygen transport, cellular respiration, and DNA synthesis. However, this same property makes excess iron toxic by generating free radicals that can damage lipid membranes, proteins, and nucleic acids leading to cell death. As a result, iron levels must be tightly regulated both on a cellular level and systemically.

We have recently discovered that the bone morphogenetic protein (BMP) signaling pathway plays an important role in systemic iron balance by modulating expression of the main iron regulatory hormone hepcidin. A soluble protein secreted by the liver, hepcidin works by blocking the iron channel ferroportin, preventing iron release into the bloodstream from dietary sources and from iron storage cells. Hepcidin expression is induced by inflammation, which is thought to be part of the host defense mechanism to fight infection and cancer by limiting iron availability. However, in chronic inflammatory states, this leads to a deficiency of iron available for red blood cell production, and this is thought be one mechanism underlying the anemia of chronic disease. In contrast, hepcidin deficiency, which causes excessive dietary iron absorption and progressive tissue iron deposition and dysfunction, appears to be the common pathogenic mechanism underlying the iron overload disorder hereditary hemochromatosis.

Our lab has recently shown that 1) mutations in either the BMP co-receptor hemojuvelin or BMP6 ligand each lead to hepcidin deficiency and severe hemochromatosis; 2) iron regulates BMP ligand expression and BMP signal transduction in the liver; and 3) modulation of the BMP signaling pathway in vivo regulates hepcidin expression and systemic iron balance. Our current focus is working to understand the molecular and cellular mechanisms by which body iron levels are sensed and how this signal is transduced to modulate hepcidin expression and maintain systemic iron balance. We are also testing BMP-hepcidin pathway modulators as new treatment strategies for anemia of chronic disease and hemochromatosis.


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Lim PJ, Duarte TL, Arezes J, Garcia-Santos D, Hamdi A, Pasricha SR, Armitage AE, Mehta H, Wideman S, Santos AG, Santos-Gonçalves A, Morovat A, Hughes JR, Soilleux E, Wang CY, Bayer AL, Klenerman P, Willberg CB, Hartley RC, Murphy MP, Babitt JL, Ponka P, Porto G, Drakesmith H
Nrf2 controls iron homeostasis in haemochromatosis and thalassaemia via Bmp6 and hepcidin.
Nat Metab. 2019;1(5):519-531 - PMID: 31276102 - PMCID: PMC6609153 - DOI: 10.1038/s42255-019-0063-6
Xiao X, Dev S, Canali S, Bayer A, Xu Y, Agarwal A, Wang CY, Babitt JL
Endothelial Bmp2 knockout exacerbates hemochromatosis in Hfe knockout mice but not Bmp6 knockout mice.
Hepatology. 2019;:ePub - PMID: 31778583 - DOI: 10.1002/hep.31048
Wang CY, Xiao X, Bayer A, Xu Y, Dev S, Canali S, Nair AV, Masia R, Babitt JL
Ablation of hepatocyte Smad1, Smad5 and Smad8 causes severe tissue iron loading and liver fibrosis in mice.
Hepatology. 2019;70(6):1986-2002 - PMID: 31127639 - PMCID: PMC6874904 - DOI: 10.1002/hep.30780
Babitt JL
Ironing out pulmonary arterial hypertension.
Proc Natl Acad Sci U S A. 2019;116(26):12604-12606 - PMID: 31171658 - PMCID: PMC6601273 - DOI: 10.1073/pnas.1908298116
Wang CY, Xu Y, Traeger L, Dogan DY, Xiao X, Steinbicker AU, Babitt JL
Erythroferrone lowers hepcidin by sequestering BMP2/6 heterodimer from binding to the BMP type I receptor ALK3.
Blood. 2019;:ePub - PMID: 31800957 - DOI: 10.1182/blood.2019002620
Leaf DE, Rajapurkar M, Lele SS, Mukhopadhyay B, Boerger EAS, Mc Causland FR, Eisenga MF, Singh K, Babitt JL, Kellum JA, Palevsky PM, Christov M, Waikar SS
Iron, Hepcidin, and Death in Human AKI.
J Am Soc Nephrol. 2019;30(3):493-504 - PMID: 30737269 - PMCID: PMC6405140 - DOI: 10.1681/ASN.2018100979
Babitt JL, Sitara D
Crosstalk between fibroblast growth factor 23, iron, erythropoietin, and inflammation in kidney disease.
Curr Opin Nephrol Hypertens. 2019;28(4):304-310 - PMID: 31145704 - PMCID: PMC6693648 - DOI: 10.1097/MNH.0000000000000514