Copper is an essential micronutrient for the normal growth and development of all aerobic organisms. Many key metabolic processes are copper-dependent, including oxidative respiration, neurotransmitter synthesis, connective tissue formation, free radical detoxification, iron homeostasis, and pigmentation. Intracellular copper levels must be tightly regulated, as a deficiency or excess of copper is deleterious to cellular function. The major goal of the lab’s research is to understand the mechanisms of copper uptake, distribution, utilization, recycling, export and regulation at the cellular and molecular level in cell culture and animal models.
Animal models of dietary or genetically imposed copper deficiency demonstrate severe cardiovascular malfunction. However, little is known about the mechanisms by which reductions in this essential metal ion lead to cardiovascular disease such as hypertrophic cardiomyopathy. The lab is interested in dissecting the precise roles for copper in mammalian copper deficiency-mediated cardiovascular abnormalities.
Recent studies suggest the possibility of a systemic copper homeostasis regulatory mechanism that allows the copper status of the heart to be communicated to tissues involved in copper uptake and storage. In collaboration with other research groups, the lab aims to decipher the mechanisms of systemic copper homeostasis between organs.
We are using C. elegans as a model to identify novel copper-regulated genes and pathways in worms that have similar roles in mammals. We conducted an RNAi screen of the human homologs identified by RNAseq for Cu-dependent growth phenotypes, and found a number of new genes required for normal growth and development of C. elegans under copper-deficient or copper-overloaded conditions. Our studies revealed that fine-tuned copper homeostasis regulation is required for normal growth in C. elegans. Currently, studies are underway for functional analysis of the top-listed candidate genes to identify novel components of the copper homeostasis at the organismal level in C. elegans.