Metal imbalances in metabolic pathology 
 

There is tantalizing evidence that zinc, copper, iron, and cadmium homeostasis play a critical regulatory in a broad range of normal physiologic functions of multiple cell types, including pancreatic beta cells, hepatocytes, adipocytes, and cardiomyocytes. The three DBPs selected as initial test beds for mapping metal distributions and interactions in relation to metabolic function vary in terms of the metals under scrutiny (Cu, Zn, Fe, and Cd) and cell type. These projects include (a) the study of interplay between heavy metal contaminants, such as cadmium, and endogenous zinc, in regulating pancreatic beta cell function; (b) the potential relationship between Fe intake and development of Type 2 diabetes; and (c) the pathologies of heart failure associated with iron accumulation in cardiomyocytes and liver failure associated with abnormal copper accumulation in congenital disorders in copper homeostasis, such as in Menkes Disease and Wilson Disease. The technical challenges they pose relate to the ability of Resource imaging modalities to accurately measure tissue and cellular distribution of multiple metals (e.g. across length scales) and under an array of physiologic and pathologic conditions.