Grant: Operating Grant

The Multidrug Resistance Proteins (MRPs), which are the focus of our research, act as energy dependent molecular pumps that can prevent drugs from reaching their targets within cells. These proteins recognize a vast array of drugs that are used to treat cancer and other diseases. When they are present in various types of tumours, they have the potential to make the tumour resistant to many commonly used chemotherapeutic agents. These proteins are also present in normal tissues and they play an important role in protection against environmental toxins, as well as potentially harmful components in the diet. However, their presence at certain locations, such as in the barriers between the blood and the central nervous system, can serve as an obstacle that limits the effectiveness of drugs that need to cross these barriers to reach their targets, such as certain drugs that are used to treat various neurological disorders. Because of their important roles in normal physiology, as well as their potential as therapeutic targets in pathological conditions, it is essential that we understand the possible consequences of manipulating the way in which these proteins function. Our research aims at understanding how the MRPs recognize their "cargo" and how they transport it across biological membranes. This research will assist in the design of drugs that will allow controlled alteration of the activity of these transport proteins and provide a greater understanding of the potential consequences of inactivating them when treating diseases such as cancer.