The long term goal of the research conducted in my lab is to learn about the general principles that organisms use to acquire and metabolize the essential nutrients iron, manganese and copper. Since in eukaryotes, iron metabolism, for example, depends on the activity of copper-containing enzymes called ferroxidases, we examine the trafficking copper in cells as well. In addition, as divalent metal ions, manganese and ferrous iron share many of the same trafficking pathways. The first challenge for a cell is to scavenge these metals from the environment. This is true for a yeast cell in culture, for an epithelial cell in your intestine, an endothelial cell in the capillaries in the brain, or a neuron. The second challenge is to efficiently and correctly partition these metals in the cell for subsequent utilization and storage. Ultimately the cell or organism will have to regulate the accumulation of these metals and to ensure that they are not allowed to roam "free" since all three are toxic.
Yet all are essential micronutrients, as well. They are required in fundamental cellular processes such as cellular respiration in all organisms, and for vital physiologic functions such as oxygen transport in blood and muscle. The brain has a strong requirement for iron and copper to support the elevated energy metabolism needed to support neuronal function; manganese is essential to neurotransmitter synthesis. This essentiality is contrasted by cytotoxicity that results from their strong tendency to generate oxygen radicals which in turn destroy key cellular components. For example, iron uptake into the brain must be tightly regulated, a process we focus in our research. Failure of this regulation can result in a variety of brain pathologies particularly those that result in degeneration of neuronal function. We study in detail the role of the amyloid precursor protein and alpha-synuclein in iron and manganese trafficking and how these functions are related these proteins' roles in neurodegenerative disease.