A
goal of my research is to gain an understanding of the structure
and functioning of the cation transporter, Na+,K+-ATPase.
This enzyme serves as the receptor of cardiac glycosides (digitalis),
a class of drugs that are widely used to treat congestive heart
failure and some arrhythmias. Specifically we are working
to elucidate the molecular structure of the enzyme’s digitalis
binding site, the mechanism of drug binding and the conformational
changes undergone by the enzyme as the drug binds and inhibits
enzyme functioning. We are using enzyme kinetics, radioligand
binding, fluorescence spectroscopy, immunochemical and computer-aided
structure modeling techniques to achieve our goal. We are
also using anti-digitalis monoclonal antibodies (mAbs) as model
drug receptors in order to better understand how in general drug-binding
sites are constructed. These same antibodies are serving
as binding templates with which to isolate short peptides that
may mimic the structures of the cardiac glycosides. These mimics
should aid our understanding of drug-receptor interactions and
possibly serve as alternatives to the plant-derived cardiotonic
steroid compounds.
Further, in a collaborative effort with investigators from the
Dept. Psychiatry and bio-technology partners we have been able
to generate and have characterized several novel human sequence
monoclonal antibodies that binding either digoxin or cocaine.
The objective of this project is to develop these antibodies as
safe therapeutic agents for the treatment in patients of drug
overdose or drug abuse, respectively. Our research approach
to all of these studies employs a variety of experimental techniques.
Publications
