ROLAND G. KALLEN, M.D., Ph.D.
Professor of Biochemistry and Biophysics
913B Stellar-Chance Building / 6059
T:(215) 898-5184, 898-8348
M.D. Columbia University College of Physicians and Surgeons (1960)
Ph.D. Brandeis University (1965)
DESCRIPTION OF RESEARCH INTERESTS:
Dr. Kallen's research deals with ion channel mediated transmembrane signal transduction. What do voltage-gated ion channels look like, how do they work in the presence and absence of modifiers and what regulates the expression of voltage-sensitive sodium channels in normal and pathologic states?
The electrical action potential responsible for muscle contraction involves the sodium channel and by employing molecular biological techniques, Dr. Kallen's lab has cloned, sequenced and overexpressed cDNA clones for these ion channels. The lab has analyzed naturally occurring human mutations and constructed site-specific mutants. In addition they have cloned and investigated the promoter regions of the genes encoding these channels. The aim of these studies are two-fold: (a) to understand the developmental regulation of the in vivo expression of channel subtypes at the transcriptional level and how the change in subtype patterns following birth and denervation is achieved; and (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. In addition, the lab has developed a mouse transgenic model of the human diseases referred to above for pathophysiological studies and to assess new therapeutic modalities.