Paul Schlesinger, M.D., Ph.D.
Associate Professor
Cell Biology and Physiology
Biochemistry Program
Molecular Cell Biology Program
Computational and Molecular Biophysics Program
BiomedRAP Program
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Office Phone: 314-362-2223
Lab Phone: 314-362-8702
Other Phone: 314-362-8703
FAX: 314-362-7463
Box: 8228
Lab Address: 401 McDonnell Medical Sciences Building
Email: pschlesinger@wustl.edu
Keywords: apoptosis; ion channel; biophysics; physiology; endocytosis
Short Research Description: Intracellular ion transport, chloride, protons, mitochondrial channels, phagosome, parasites. |
Research Abstract:
My research has focused on intracellular transport of ions, including protons, their influence on the physiology of cells. Over the years this has included the acidification of intracellular vesicles, chloroquine transport and resistant malaria parasites, intracellular mycobacteria, bone resorption, intracellular chloride channels, membrane channels and pores formed by Bcl-2 family proteins in apoptosis and the synthesis and characterization of synthetic channels. Currently we are actively studying the ion transport of bone resorption with a major emphasis on the expression of the proton pump and it regulation via intracellular chloride channels. In a second project we are characterizing the pore formation and cytchrome c transport by Bcl-2 family proteins in liposomes and mitochondria. They are primarily biophysical and biochemical studies on the mechanism of pore formation by these membrane proteins and in particular on the activiation of Bax the major proapoptotic regulator. The last project I will describe is the synthesis and characterization of synthetic ion channels. We are using this as a way to study and understand the chemical factors which contribute to ion channel transport through membranes. As we have developed these compounds, they are being applied to the study of cellular ion homeostasis and as reagents against bacteria and cells.
In addressing these questions, my laboratory has applied numerous techniques ranging from cell and molecular biology, biophysical chemistry, molecular modeling and electrophysiology. |
Selected Publications:
Soman NR, Baldwin S, Hu G, Marsh JM, Lanza GM, Heuser JE, Arbeit JM, Wickline SA and Schlesinger PH. Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth. J. Clin. Invest. 2009 119:2830-42.
Ivashyna O, Garcia-Saez AJ, Ries J, Christensen E, Schwille P, Schlesinger PH. Detergent-activated BAX Protein Is a Monomer. J. Biol. Chem. 2009 Sep4; 284(36): 23935-23946.
Olsen BN, Schleisnger PH and Baker HA. Perturbations of membrane structure by cholesterol and cholesterol derivatives are determined by sterol orientation. J. Am. Chem. Soc. 131:4854-4865.
Christenson E, Merlin S, Saito M, Schlesinger PH. Cholesterol Effects on Bax Pore Activation J. Mol. Biol. 2008 381:1168-1183.
Saito M, Korsmeyer SJ, Schlesinger PH. BAX dependent cytochrome-c transport reconstituted in pure liposomes. Nat Cell Biol 2000 2:553-555. |