Faculty Research Brief: Dr. Ningning Zhao
Dr. Ningning Zhao has received training in human physiology, biochemistry, nutritional science, molecular biology and cell biology that he is now applying to the research of biomedical questions relevant to human diseases. The long-term goal of his research is to advance the understanding of disease mechanisms, identify therapeutic target genes, and improve the life quality of patients. His current research interests focus on metal transport proteins. Mutations and malfunctioning of membrane metal transporters is closely related to the initiation and the progression of an increasing number of human diseases, including hereditary hemochromatosis, cancer, and neurodegeneration. The Zhao laboratory is focused on advancing molecular mechanisms for the function and regulation of plasma membrane metal transporters. His most recent research program aims to investigate the mechanisms underlying the regulation of a newly identified metal transport protein, ZIP14, and to examine the function of ZIP14 in establishing metal homeostasis in the body.
ZIP14 possesses unique functions in mediating body metal homeostasis: it can transport zinc, iron, manganese, and cadmium; it mediates both transferrin-bound iron and non-transferrin-bound iron uptake into cells; it is the only metal importer identified to date that is upregulated by excess iron, suggesting that ZIP14 contributes to tissue iron loading under high iron conditions, such as hereditary hemochromatosis; mutations in ZIP14 result in early-onset neurodegeneration associated with brain manganese accumulation in humans. Despite the clear importance for human health, the precise role of ZIP14 in establishing body metal homeostasis remains unknown. Dr. Zhao’s research has identified a novel iron-dependent proteasome-mediated pathway for regulating the degradation of ZIP14. A critical next step will be to understand the detailed mechanism of this regulation. Data from his studies suggest that two novel topics are involved in the regulation of ZIP14: membrane dislocation and the tumor suppressor p53. His laboratory is conducting a more complete examination of the mechanisms underlying the regulation and the degradation process of ZIP14.