Research Summary
Dr. Lutsenko's research 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 results 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, Dr. Lutsenko and her research team 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.
Lab
The long-term goal of Dr. Lutsenko's laboratory is to provide a detailed understanding of human copper homeostasis in health and disease.
The group focuses on:
- Structure, function and regulation of human copper transporters. Scientists study the function and regulation of two copper-transporting ATPases, ATP7A and ATP7B, in different cell types. They use a combination of biochemical, biophysicalw and cell biological approaches to understand the copper transport mechanism, and to examine the effect of various mutations on the structure and activity of copper transporters.
- Copper chaperones. They are characterizing the functional interactions and the mechanism of copper transfer between the human copper chaperone Atox1 and the copper transporters ATP7A and ATP7B.
- Molecular mechanisms of Wilson’s disease. They utilize the genetically engineered Atp7b-/- mice to better understand (1) the molecular and cellular events that trigger the onset of Wilson’s disease pathology in different tissues, (2) the mechanism of disease progression and (3) the role of various metabolic pathways in determining the severity of the disease.
Lab Website: Svetlana Lutsenko Laboratory
Selected Publications
Gray LW, Peng F, Molloy SA, Pendyala VS, Muchenditsi A, Muzik O, Lee J, Kaplan JH, Lutsenko S. "Urinary copper elevation in a mouse model of Wilson's disease is a regulated process to specifically decrease the hepatic copper load." PLoS One. 2012;7(6):e38327. doi: 10.1371/journal.pone.0038327. Epub 2012 Jun 22.
Schushan M, Bhattacharjee A, Ben-Tal N, Lutsenko S. "A structural model of the copper ATPase ATP7B to facilitate analysis of Wilson disease-causing mutations and studies of the transport mechanism." Metallomics. 2012 Jul;4(7):669-78. doi: 10.1039/c2mt20025b. Epub 2012 Jun 13.
Hatori Y, Clasen S, Hasan NM, Barry AN, Lutsenko S. "Functional partnership of the copper export machinery and glutathione balance in human cells." J Biol Chem. 2012 Aug 3;287(32):26678-87. doi: 10.1074/jbc.M112.381178. Epub 2012 May 30.
Hasan NM, Gupta A, Polishchuk E, Yu CH, Polishchuk R, Dmitriev OY, Lutsenko S. "Molecular events initiating exit of a copper-transporting ATPase ATP7B from the trans-Golgi network." J Biol Chem. 2012 Oct 19;287(43):36041-50. doi: 10.1074/jbc.M112.370403. Epub 2012 Aug 16.
Gupta A, Bhattacharjee A, Dmitriev OY, Nokhrin S, Braiterman L, Hubbard AL, Lutsenko S. "Cellular copper levels determine the phenotype of the Arg875 variant of ATP7B/Wilson disease protein." Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5390-5. doi: 10.1073/pnas.1014959108. Epub 2011 Mar 15.
Burkhead JL, Gray LW, Lutsenko S. "Systems biology approach to Wilson's disease." Biometals. 2011 Jun;24(3):455-66. doi: 10.1007/s10534-011-9430-9. Epub 2011 Mar 5. Review.
Burkhead JL, Ralle M, Wilmarth P, David L, Lutsenko S. "Elevated copper remodels hepatic RNA processing machinery in the mouse model of Wilson's disease." J Mol Biol. 2011 Feb 11;406(1):44-58. doi: 10.1016/j.jmb.2010.12.001. Epub 2010 Dec 10.
