Grant: Operating Grant

The P-glycoprotein drug pump is a critical defense mechanism because it is found at high levels in the lining of the intestine,in the kidney and liver, and at the blood-brain barrier where it functions to block entry or extrude toxins found in food or the environment from entering our body or brain. If you eat a food that contains a toxin (many plants produce toxins to protect themselves from being eaten), then P-glycoprotein in the intestine will prevent these toxins from being absorbed. If toxins do enter your bloodstream then P-glycoprotein expressed in the liver or kidney will extract these chemicals from the bloodstream so that they will be eliminated in the urine (kidney) or bile (liver).P-glycoprotein can cause problems in treatments for diseases such as cancer or brain diseases however, because it prevents therapeutic drugs from entering cancer cells or getting into the brain. The long-term goals of Dr. David Clarke's laboratory are to determine how P-glycoprotein is able to pump so many different kinds of drugs and to find out ways to turn it off during treatment of diseases. The ability to turn off this drug pump would improve the effectiveness of cancer chemotherapy, treatments for brain disorders as well as treatments for other diseases.