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Paul
J. De Weer, M.D., Ph.D.
Professor, Dept of Physiology
School of Medicine
504 Goddard Building
(215) 898-0044 FAX: (215) 573-5851
email: deweer@mail.med.upenn.edu
Click here for selected publications since Dr. De Weer's arrival at Penn
RESEARCH INTERESTS
Biochemical and biophysical mechanisms, kinetics, thermodynamics, and structure
of the electrogenic sodium pump. RESEARCH TECHNIQUES
Intracellular perfusion/dialysis; voltage clamp and radioisotope flux measurement techniques; transient and steady-state kinetic techniques; mathematical/kinetic modeling.RESEARCH SUMMARY
Research in this laboratory is directed towards understanding the sodium pump or Na/K-ATPase, a ubiquitous integral membrane enzyme that carries out the active electrogenic translocation of Na+ and K+ ions across the plasma membrane of most animal cells, and which is the pharmacological target of cardiotonic steroids. Main interests are the kinetics, energetics, and voltage dependence of the multiple steps in the transport cycle. Part of the research uses giant nerve fibers from the squid, which are particularly well suited for such techniques as microinjection, internal perfusion, and voltage clamping. By exerting experimental control over electrical, biochemical, and ionic parameters, the investigator is able to study electrogenic ion transport in a way impossible to achieve in small cells. Parallel research is done on Na/K-ATPase purified from squid brain, and involves steady-state and rapid-kinetic analysis and modeling. The goal is to identify the multiple biochemical (phosphorylation; dephosphorylation; ligand binding, etc.) events that take place during active transport, and to correlate them with biophysical observables such as electrogenic currents, charge translocating transients, and isotope fluxes.
KEY WORDS:
Transport; sodium pump; kinetics
