Iron is an essential metal required for many cellular processes, including hemoglobin synthesis in red blood cells; excess iron, however, causes oxidative damage that can lead to organ failure. Our laboratory is interested in elucidating the molecular mechanisms that regulate systemic iron balance through genetic study of patients with iron disorders and through phenotypic characterization of genetically engineered mouse models.
By studying families with an unusual, inherited form of iron deficiency anemia, we have identified TMPRSS6, a transmembrane serine protease expressed in the liver, as an essential regulator of iron balance. Using genetically targeted mouse models, we have found that Tmprss6 acts to regulate iron balance by dampening bone morphogenetic protein (BMP) signaling pathway in the liver. We have also found that genetic loss of Tmprss6 can modify disease severity in mouse models of human iron overload disorders, suggesting Tmprss6 as a potential therapeutic target in these disorders.