UGT Enzymes In Chemotherapeutic Drug Metabolism: New Avenues To Improve Drug Response And Overcome Resistance
Funder
National Health and Medical Research Council
Funding Amount
$610,005.00
Summary
Tumours treated by chemotherapy often become resistant to the drugs, leading to relapse and reduced chance of survival. We will study one of the main pathways leading to drug resistance, which could lead to the development of new ways to overcome resistance and improve cancer treatment outcomes.
Over-expression Of Human Cytochrome P450 2J2 Activates Phase II Biotransformation Genes That Influence Anti-cancer Drug Efficacy
Funder
National Health and Medical Research Council
Funding Amount
$489,155.00
Summary
Increased expression of some enzymes in human tumours contributes to anticancer drug resistance. In many tumours the fatty acid epoxygenase cytochrome P450 2J2 (CYP2J2) is over-expressed. We have found that CYP2J2 activates the expression of phase II enzymes that eliminate anticancer drugs; this is mediated by fatty acid epoxides. In this project we will define the underlying mechanisms of these effects, which may lead to novel strategies to overcome anticancer drug resistance.
A Novel Metabolic Role For UDP Glycosyltransferase 8 (UGT8)
Funder
National Health and Medical Research Council
Funding Amount
$419,144.00
Summary
The UDP glycosyltransferases (UGTs) are a family of enzymes that remove drugs and toxins from the human body as well as control levels of naturally produced molecules such as bile acids and hormones. We found that a new member of this family called UGT8 processes bile acids in the kidney and intestine and can affect how bile acids act to regulate metabolism. Our studies uncover new roles for bile acids in liver, kidney and gut health and in metabolic disorders such as diabetes and obesity.
Regulation Of Drug Detoxifying UDP Glucuronosyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$590,945.00
Summary
Some organs in the body are particularly sensitive to fat-soluble chemicals taken in from the environment or present in food. They are also sensitive to hormones and other small molecule products of metabolism. Controlling the levels of these potentially toxic chemicals is essential in order to maintain the health of the organ. In this work we will investigate the regulation of detoxifying enzymes that protect these organs by inactivating and hastening the elimination of fat-soluble chemicals.