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Roland
G. Kallen, M.D., Ph.D.
Professor, Dept of Biochemistry & Biophysics
913B Stellar-Chance Bldg.
422 Curie Blvd
Philadelphia, PA 19104-6059
Tel: 215-898-5184 Fax: 215-573-7058
E-mail: rgk@mail.med.upenn.edu (internet)
http://www.med.upenn.edu/bmbgrad/Faculty/Master_List/Kallen/kallen.html
/ins/faculty/kallen.htm
Click here for selected publications since Dr. Kallen's arrival at Penn
RESEARCH INTERESTS
Ion channel mediated transmembrane signal transduction. What do channels look like, how do they work in the presence and absence of modifiers and what regulates their expression of voltage-sensitive sodium channels in normal and pathologic states?RESEARCH TECHNIQUES
Recombinant DNA (DNA, RNA, protein blots, site-specific mutagenesis, purification and characterization of nucleic acids and proteins, exploitation of expression and overexpression systems, etc.); tissue culture (skeletal muscle and cardiac cells); cytochemistry involving antibody and nucleic acid probes; analysis of transgenic animals expressing abnormal channels; generation and expression of synthetic mRNAs in oocytes, and mammalian cells; voltage- and patch-clamp analysisRESEARCH SUMMARY
Skeletal muscle, brain and cardiac voltage-dependent sodium channels:
The electrical action potential responsible for muscle contraction involves the sodium channel and by employing molecular biological techniques we have cloned, sequenced and overexpressed cDNA clones for these ion channels. We have analyzed naturally occuring human mutations and constructed site-specific mutants. In addition we have cloned and investigated the promoter regions of the genes encoding these channels. The aim of these studies are two-fold: (a) to understand how the change in subtype patterns following birth and denervation affects organ function; (b) to study the biochemistry of the channels via structure-function correlations which will enable an understanding of which parts of the molecule are involved in various channel states (activated, inactivated, closed), sites of drug and toxin binding, and the topological arrangement of the channel in the membrane. These studies may help to understand why there are so many different channel subtypes and to determine the defects in sodium channels associated with human diseases such as familial hyperkalemic periodic paralysis and paramyotonia congenita, which we have shown to be linked to one sodium channel gene and for which we have developed a transgenic mouse model. This will enable pathophysiological studies and allow us to assess new therapeutic modalities. Finally, we are exploring the use of fluorescence resonance energy transfer measurements, which will give distance measurements between specifically labeled sites on the channel, created by recombinant DNA methods. This promises to provide a quantum jump in our comprehension of the detailed 3-D structure. This is a prerequisite for understanding how these important membrane proteins work.
KEY WORDS:
Structure; function; expression; ion channels
