My laboratory is focused on elucidating the molecular and cellular mechanisms involved in iron homeostasis.
Jodie L. Babitt, MD
Assistant Professor of Medicine
185 Cambridge Street, CPZN 8.218
Boston, MA 02114
Phone: (617) 643-3181
Fax: (617) 643-3182
My laboratory is focused on elucidating the molecular and cellular mechanisms involved in iron homeostatis. Our ultimate goal is to identify new treatment strategies for disorders of iron homeostatis, such as the anemia of chronic disease (including the anemia of chronic kidney disease) and the iron overload disorder homeostasis.
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 in 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 availablity. However, in chronic inflammatory states, this leads to a deficiency of iron available for red blood cell production, and this is thought to be one mechanism underlying the anemia of chronic disease, including the anemia of chronic kidney 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.
Babitt JL, Zhang Y, Samad TA, Xia Y, Tang J, Campagna JA, Schneyer AL, Woolf CJ, and Lin HY. Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor. J. Biol. Chem. 2005. 280(33) 29820-7.
Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, Campagna JA, Chung RT, Schneyer AL, Woolf CJ, Andrews NC, and Lin HY. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat. Genet. 2006. 38(5): 531-9.
Babitt JL, Huang FW, Xia Y, Sidis Y, Andrews NC, and Lin HY. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J. Clin. Invest. 2007. 117(7): 1933-9.
Andriopoulos B Jr, Corradini E, Xia Y, Faasse SA, Chen S, Grgurevic L, Knutson MD, Pietrangelo A, Vukicevic S, Lin HY, and Babitt JL. BMP 6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet. 2009. 41(4): 482-7.
Corradini E, Garuti C, Montosi G, Ventura P, Andriopoulos B Jr, Lin HY, Pietrangelo A, and Babitt JL. Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of hemochromatosis. Gastroenterology. 2009. 137(4): 1489-97.
Babitt JL and Lin HY. Molecular mechanisms of hepcidin regulation: implications for the anemia of chronic kidney disease. Am J Kidney Dis. 2009. In Press