PRIMARY FACULTY

Saibal Dey, Ph.D.
Associate Professor
Biochemistry
 
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-3449
Fax: 301-295-1996
sdey@usuhs.mil
 
More about Dr. Dey's Research

The effectiveness of anti-microbial and anti-cancer chemotherapy largely depends on the ability of the therapeutic agents to reach their sites of action. Following administration, the fate of a drug molecule depends on how well it is absorbed from its site of administration, its distribution pattern, the extent and nature of its biotransformation, and on the efficiency by which it is excreted. Even when these obstacles are surpassed, the therapeutic potency of a drug could be profoundly affected by occurrence of intrinsic as well as acquired drug resistance in the target cells. Thus, strategic development of chemotherapeutic drugs has to continuously battle against poor bioavailability and occurrence of drug resistance. The role of the human multidrug transporter P-glycoprotein (Pgp) in both of these phenomena is rapidly unfolding. Functionally, Pgp is an ATP-dependent efflux pump for an inordinately wide range of structurally unrelated hydrophobic drugs including anti-cancer and anti-HIV agents.
 

 
In order to retain the therapeutic effectiveness of chemotherapeutic agents, a major effort is underway to selectively inhibit the function of Pgp in tumor cells as well as in certain normal tissues. Although random screening of natural products and synthetic libraries have shown some promise, a better understanding of the mechanism of Pgp-mediated drug transport is necessary for developing inhibitors with improved efficacy.

Research goals of my laboratory are directed towards 1) elucidation of the molecular mechanism involved in coupling of ATP hydrolysis to drug translocation by Pgp, 2) characterization of its functional regulation by pharmacological agents as well as endogenous molecules and 3) identification of novel therapeutic targets within the protein. We use a vaccinia virus mediated infection transfection protocol for generation of recombinant Pgp molecules and for their rapid biochemical characterization. Baculovirus-mediated expression, in insect cells, allows large-scale production of the protein. Purification and functional reconstitution of Pgp can be achieved by metal-chelate chromatography.

Selected Publications

Resources