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:
Leevy WM, Donato GM, Ferdani R, et al. Synthetic hydraphile channels of appropriate length kill Escherichia coli. J Am Chem Soc 2002 124:9022-9023.
Schlesinger PH, Ferdani R, Liu J, et al. SCMTR: A chloride-selective, membrane-anchored peptide channel that exhibits voltage gating. J Am Chem Soc 2002 124:1848-1849.
Saito M, Korsmeyer SJ, Schlesinger PH. BAX dependent cytochrome-c transport reconstituted in pure liposomes. Nat Cell Biol 2000 2:553-555.
Schlesinger PH, Blair HC, Teitelbaum SL, Edwards JC. The chloride channel of osteoclast ruffled borders: Molecular characterization and role in bone resorption. J Biol Chem 1997 272:18636-18643.
Mattsson JP, Schlesinger PH, Keeling DJ, et al. Isolation and reconstitution of a vacuolar-type proton pump of osteoclast membranes. J Biol Chem 1994 269:24979-24982.
Last Updated: 06/20/2007 |