The research in Dr. Svetlana Lutsenko's laboratory is focused on molecular mechanisms that regulate copper concentration in normal and diseased human cells. Copper is essential for human cell homeostasis. It is required for embryonic development and neuronal function, and disruption of copper transport in human cells result in severe multi-system disorders such as Menkes disease and Wilson's disease. To understand the molecular mechanisms of copper homeostasis in normal and diseased human cells we utilize multidisciplinary approach involving biochemical and biophysical studies of molecules involved in copper transport, cell biological studies of copper signaling, and analysis of copper-induced pathologies using Wilson's disease gene knock-out mice. Several projects are currently underway in the laboratory:

1. Characterization of the functional properties of the Wilson's disease protein (WNDP), a human copper-transporting ATPase ATP7B. We have developed a robust system for expression of WNDP in insect cells ([PubMed], [PDF]). More...

2. Another important direction in the laboratory is the investigation of copper delivery to WNDP mediated by human copper-chaperone chap. We demonstrated that chap acts as a regulator of catalytic activity of WNDP ([PubMed], [PDF]). More...

3. Copper signaling in human cells. This is a fairly recent area of our research, which was initiated following our discovery of the copper-dependent phosphorylation of WNDP by a kinase ([PubMed], [PDF]). In these studies, we seek to identify the kinase that phosphorylates WNDP, to understand the molecular mechanisms of copper-dependent phosphorylation and to isolate proteins that regulate WNDP. More...

4. The molecular and biochemical basis of the Wilson's disease pathology. For these studies we use a genetically engineered Wilson's disease gene knock-out mice ([PubMed], [PDF]), mRNA microarray analysis, and real-time PCR. More...

5. The role of copper in the brain. Neurological, development and behavior abnormalities are frequent symptoms of Menkes and Wilson's disease. To understand how copper is distributed in the brain and how changes in copper concentration lead to various human pathologies we map the specific location of the copper transporters using fluorescent in situ hybridization. More...