Tracey A. Rouault, MD, Program Head
Researchers in the Program in Molecular Medicine seek to understand mechanisms of disease through analysis of mouse models and work on human patients. Abnormalities of metal homeostasis, including the role of iron misregulation in pathogenesis of neurodegeneration and refractory anemias, and the role of copper transport abnormalities in Menkes disease and related conditions, are under investigation.
Tracey Rouault's Section on Human Iron Metabolism studies mammalian iron metabolism by using mouse models and tissue culture. Rouault previously identified and characterized two major cytosolic iron regulatory proteins (IRPs). Targeted deletion of each IRP in mice revealed that misregulation of iron metabolism due to loss of IRP2 causes functional iron deficiency, erythropoietic protoporphyria, anemia, and neurodegeneration in animals. The Section also focuses on mammalian iron-sulfur cluster assembly, and its researchers have characterized numerous mammalian genes involved in iron-sulfur cluster synthesis, developing in vitro and in vivo methods to assess cluster biogenesis. Their discoveries may promote understanding and treatment of neurodegenerative diseases, especially Parkinson's disease and Friedreich ataxia, and hematologic disorders such as refractory anemias, and erythropoietic protoporphyria, and some rare myopathies.
Stephen Kaler's Section on Translational Neuroscience studies human disorders of copper transport, including Menkes disease, occipital horn syndrome, and distal motor neuropathy. Kaler previously defined the molecular basis for occipital horn syndrome and is principal investigator on the lead protocol in the United States for treatment of Menkes disease. Taking a translational research approach, we seek to identify and characterize under-appreciated cellular and genetic phenomena suggested by patients' phenotypes or their responses to treatment. We use yeast strains and mouse models to evaluate copper transport and test novel therapeutic approaches.