Dr. Gitlin’s laboratory is interested in fundamental aspects of human nutrition. Copper is an essential nutrient that plays a critical role in the biochemistry of all aerobic organisms. Proteins exploit the unique redox nature of copper to undertake a series of facile electron transfer reactions required for cellular respiration, iron homeostasis, pigment formation, neurotransmitter production, peptide biogenesis, connective tissue biosynthesis, and antioxidant defense. The reactivity of copper in biological systems also accounts for the potential toxicity of this metal when cellular copper homeostasis is disturbed. For this reason, specific pathways have evolved for the trafficking and compartmentalization of copper within cells.

One goal of the lab’s studies is to understand the pathways of nutrient trafficking and metabolism at the cellular and molecular level. As a starting point, they have focused on the inherited disorders of copper metabolism in humans, defining the molecular genetics including two copper-transporting P-type ATPases and a novel family of proteins termed copper chaperones that deliver copper to specific targets within the cell. Elucidation of the structure and function of these proteins reveals a remarkable evolutionary conservation of the mechanisms of copper metabolism and provides a useful heuristic paradigm for understanding cellular nutrient metabolism.

Another goal is to understand the role of nutrition in early human development. The human disorder Menkes disease reveals a critical role for copper in early central nervous system development, and mice with a genetic deletion of the copper chaperone atox1 demonstrate an essential role for copper in perinatal development. Utilizing zebrafish as a model vertebrate organism and taking advantage of the tools of chemical genomics, Dr. Gitlin’s lab has developed pharamacologic methods to perturb copper homeostasis in the yolk sac and thus dissect the precise role of copper in vertebrate development and organogenesis. They are now placing these observations in a broader biological context through a critical analysis of many nutrients in early embryonic development and organogenesis in the zebrafish embryo.