Dr. Byung-Eun Kim has been awarded a $1.39 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, NIH (NIDDK/NIH) for his R01 grant proposal entitled, “Systemic Copper Homeostasis Regulation in Mammals.”
Copper (Cu) is an essential trace element for normal growth and development. The dysregulation of Cu homeostasis causes severe human diseases that include Menkes disease, Wilsonʼs disease, myeloneuropathy, and cardiomyopathy. Cells have evolved sophisticated homeostatic mechanisms for the regulation of Cu acquisition and distribution, and organs communicate to ensure that Cu is distributed appropriately throughout the body, balancing cellular requirements.
All organismal Cu must pass through the intestine prior to distribution to other tissues. Therefore, cross-communication must take place among tissue types to ensure that Cu import and export from the intestine are coordinated with extra-intestinal tissue Cu requirements. In this project, Dr. Kim has proposed an inter-organ regulatory mechanism for Cu homeostasis, as the cardiac-specific knockout mouse of the high-affinity Cu importer, Ctr1 exhibited dramatically elevated levels of the ATP7A Cu efflux pump in the liver and intestine, suggesting the existence of an organismal level Cu sensing signal that communicates a cardiac Cu deficiency to the primary site of Cu storage and uptake organ.
The studies in this project aim to uncover cellular and inter-organ Cu homeostasis mediated by Cu transporters using a combination of mouse physiology and C. elegans genetics to allow better diagnosis and treatment of diseases caused by Cu imbalance.