Stephan Wilkens, PhD

Stephan Wilkens, PhD
Appointed 07/01/05
4237 Weiskotten Hall
766 Irving Ave.
Syracuse, NY 13210

315 464-8703

Current Appointments

Hospital Campus

  • Downtown

Research Programs and Affiliations

  • Biochemistry and Molecular Biology
  • Biomedical Sciences Program
  • Cancer Research Institute
  • Research Pillars

Education & Fellowships

  • Postdoctoral Fellow: University of Oregon, Institute of Molecular Biology
  • PhD: Freie University of Berlin, 1995

Research Interests

  • Structure and Mechanism of Membrane Bound Transport Proteins

Publications

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Research Abstract

Research in my laboratory is aimed at the structural characterization of a class of proteins called transport ATPases. Transport ATPases are membrane bound enzymes, which catalyze the active transport of inorganic and organic molecules across biological membranes, a process vital to all forms of life. Many transport ATPases are key players in some of the most devastating human diseases such as cancer and AIDS. If we want to be able to fight these diseases on a molecular level (for example by drug design) we have to first understand the structure and mechanism of the disease causing proteins. Currently, we are working on two members of the transport ATPase family, the vacuolar ATPase (V-ATPase) and P-glycoprotein (Pgp; also called multi drug resistance protein). We are using cryo electron microscopy and protein NMR spectroscopy as well as biochemical and molecular biological techniques to obtain structural information for these two and related proteins.

The vacuolar ATPase (V-ATPase) is a large multisubunit protein complex found in the endomembrane system of eukaryotic organisms where it functions to acidify a variety of intracellular compartments. The vacuolar ATPase is a rotary molecular motor: ATP hydrolysis taking place on the membrane extrinsic V1 domain is coupled to ion translocation across the membrane embedded V0 via rotation of a central stalk domain. We are trying to visualize the structural changes the enzyme is undergoing during catalysis and activity silencing by reversible dissociation.

P-glycoprotein (Pgp), a member of the ABC (ATP Binding Cassette) transporter family, is an enzyme found in the cell membrane of higher organisms where it is responsible for exporting organic molecules from the interior of the cell. In animals and human, Pgp plays an important role in excretion of and protection from environmental toxins; when expressed in cancerous cells, it can lead to failure of chemotherapy by preventing the anti cancer drugs from reaching their targets inside the cells. We are using crystallographic methods in order to investigate how ATP hydrolysis in the two nucleotide binding domains allows P-glycoprotein to flip a wide variety of structurally different drugs from the inner to the outer leaflet of the plasma membrane.

Selected References:

Zhang Z, Zheng Y, Mazon H, Milgrom E, Kitagawa N, Kish-Trier E, Heck AJ, Kane PM, Wilkens S. Structure of the yeast vacuolar ATPase. J Biol Chem. 2008 Dec 19;283(51):35983-95. Epub 2008 Oct 27.

Bhardwaj A, Walker-Kopp N, Wilkens S, Cingolani G. Foldon-guided self-assembly of ultra-stable protein fibers. Protein Sci. 2008 Sep;17(9):1475-85. Epub 2008 Jun 5.

Lee JY, Urbatsch IL, Senior AE, Wilkens S. Nucleotide-induced structural changes in P-glycoprotein observed by electron microscopy. J Biol Chem. 2008 Feb 29;283(9):5769-79. Epub 2007 Dec 19.

Kitagawa N, Mazon H, Heck AJ, Wilkens S. Stoichiometry of the peripheral stalk subunits E and G of yeast V1-ATPase determined by mass spectrometry. J Biol Chem. 2008 Feb 8;283(6):3329-37. Epub 2007 Nov 30.

Kish-Trier E, Briere LK, Dunn SD, Wilkens S. The stator complex of the A1A0-ATP synthase--structural characterization of the E and H subunits. J Mol Biol. 2008 Jan 18;375(3):673-85. Epub 2007 Nov 1.
Faculty Profile Shortcut: http://www.upstate.edu/faculty/wilkenss
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