Svetlana Lutsenko Laboratory, Johns Hopkins University

Program Project Grant

The Program Project “Metal Ion Regulation in Human Cells” brings together efforts of several research laboratories to understand the molecular mechanisms of copper and iron homeostasis in human cells. Disruptions of metal homeostasis are being increasingly invoked as the basis for a number of neurodegenerative and other life-threatening diseases. The goal of this project is to dissect the mechanisms regulating metal concentration in human cells at the structural, biochemical, and cell biological levels and to provide this important information to biomedical community. This interdisciplinary program involves investigations of structure and metal-ion coordination for several physiologically important metalloproteins, understanding the molecular mechanisms of copper and iron transport in mammalian cells, and analysis of copper-mediated signaling in normal and diseased human cells. In addition to collaborative investigations, the PPG researchers participate in the “Metal and Membranes Journal Club” and have Seminar Series dedicated to recent advances in the area of human metal homeostasis. The Metal Ion Core facilitates the research of PPG investigators.

Molcules and processes studied

MEMBERS AND PROJECTS

PROJECT 1: STRUCTURAL BIOLOGY OF COPPER HOMEOSTASIS

PI: Vinzenz M. Unger, PhD

Professor

Northwestern University

http://www.ibis.northwestern.edu/faculty/unger.html

PROJECT 2: CHAPERONE – TARGET INTERACTIONS

PI: Ninian J. Blackburn, PhD

Oregon Health & Sciences University

Professor

http://www.ogi.edu/people/dsp_person.cfm?person_id=411D62AF-2A56-D16D-5CE242929E5203FA

PROJECT 3: COPPER ENTRY INTO HUMAN CELLS

PI: Jack H. Kaplan, PhD, FRS

Professor and Chair

University of Illinois in Chicago

http://www.uic.edu/com/bcmg/kaplan.html

PROJECT 4: REGULATORY ROLE OF COPPER IN HUMAN CELLS

PI: Svetlana Lutsenko, PhD

Professor

Johns Hopkins University

http://biolchem.bs.jhmi.edu/bcmb/Pages/faculty/faculty_detail.aspx?FID=345

PROJECT 5: PROTEINS REGULATING Cu-ATPases IN EPITHELIA
PI: Ann L Hubbard, PhD

Professor

Johns Hopkins University

http://cmm.jhu.edu/index.php?title=Ann_L._Hubbard

SUB-CONTRACT TO PROJECT: NMR STUDIES OF COPPER-HANDLING PROTEINS
PI: Oleg Y.Dmitriev

Associate Professor

University of Saskatoon

http://www.medicine.usask.ca/research/health-research-groups/molecular-design-research-group-1/group-members/oleg-dmitriev-1

METAL ION CORE

Lelita Braiterman, PhD (Director)

Abigael Muchenditsi, PhD (Research Associate)

Recent Collaborative Publications from PPG:

De Feo, CJ., Aller, SG., Siluvai, GS., Blackburn, NJ, and Unger, V. M. (2009) Three-Dimensional Structure Of The Human Copper Transporter hCtr1, PNAS 106, 4237-4242 PMID: 19240214
Kaplan JH, Lutsenko S. Copper Transport In Mammalian Cells: Special Care For A Metal With Special Needs (2009).J Biol Chem. 284(38):25461-5. PMID: 19602511
Barnes N, Bartee My, Braiterman L, Gupta A, Ustiyan V, Zuzel V, Kaplan JH, Hubbard AL, Lutsenko S. (2009) Cell-Specific Trafficking Suggests A New Role For Renal Atp7b In The Intracellular Copper Storage. Traffic 10(6):767-79. PMID: 19416479
Leshane ES, Shinde U, Walker JM, Barry AN, Blackburn NJ, Ralle M, Lutsenko S. (2010) J Biol Chem. 285(9):6327-36.PMID: 20032459
LutsenkoS, Bhattacharjee A, Hubbard AL (2010) Copper Handling Machinery of The Brain Metallomics (In Press)
Ralle M, Hustee D, Vogt S, Schirrmeister W, Burkhead JL, Capps TR, Gray L, Lai B, Maryon E, and Lutsenko S (2010) Wilson’s Disease At a Single Cell Level: Intracellular Copper Trafficking Activates Compartment-Specific Responses in Hepatocytes J. Biol. Chem (in press) http://www.ncbi.nlm.nih.gov/pubmed/20647314

Lutsenko Lab
Department of Physiology
Johns Hopkins University
725 N. Wolfe Street
203 Hunterian
Baltimore, MD 21205
(410) 614-4661 (tel)
(410) 955-0461 (fax)