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.
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.
Characterization Of The Novel Drug And Xenobiotic Metabolizing UGT3A Enzyme Family
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
The elimination of chemicals made in the body or from environmental sources is essential for the maintenance of good health and the prevention of debilitating diseases. We have discovered two enzymes that use glucose and other sugars to detoxify fat-soluble chemicals. In this project we will study how these enzymes work and how they are regulated in the body. With this knowledge, we may be able to target the processes of drug and chemical detoxification to make them more efficient.
UDP Glucuronosyltransferases As Regulators Of Signaling Pathways Modulated By Chemical Ligands.
Funder
National Health and Medical Research Council
Funding Amount
$500,460.00
Summary
Cells respond to their surroundings by transferring information received at the cell surface to the nucleus leading to changes in gene expression. There are many signaling pathways which transfer this informatrion to the nucleus. Some of these pathways are controlled by small molecules, usually fat-soluble chemicals. As a family of enzymes, the UDP glucuronosyltransferases (UGT) have evolved to eliminate fat-soluble chemicals, we propose that UGTs play a pivotal role in regulating the concentrat ....Cells respond to their surroundings by transferring information received at the cell surface to the nucleus leading to changes in gene expression. There are many signaling pathways which transfer this informatrion to the nucleus. Some of these pathways are controlled by small molecules, usually fat-soluble chemicals. As a family of enzymes, the UDP glucuronosyltransferases (UGT) have evolved to eliminate fat-soluble chemicals, we propose that UGTs play a pivotal role in regulating the concentrations of fat-soluble chemicals involved in signaling, and thus are important in controlling gene expression. We intend to provide evidence for this novel role of UGTs in this project. This information will be used to alter the response of the cell to its environment. For example, to help protect the cell against environmental toxins, or to make a cancer cell more susceptible to a chemotherapeutic agent.Read moreRead less
Molecular Determinants Of UDP Glucuronosyltransferase 1A3 And 1A4 Expression
Funder
National Health and Medical Research Council
Funding Amount
$516,078.00
Summary
Enzymes in the liver and gastrointestinal tract have a crucial role in protecting against the toxic effects of fat-soluble chemicals. Two of these enzymes called UGT1A3 and UGT1A4 have a special role in protecting against drugs and toxins that contain nitrogen groups. The levels of these two enzymes in the liver and gut vary extensively between individuals. In this project we will determine how the levels of these enzymes are controlled and what is the cause of this variability between individua ....Enzymes in the liver and gastrointestinal tract have a crucial role in protecting against the toxic effects of fat-soluble chemicals. Two of these enzymes called UGT1A3 and UGT1A4 have a special role in protecting against drugs and toxins that contain nitrogen groups. The levels of these two enzymes in the liver and gut vary extensively between individuals. In this project we will determine how the levels of these enzymes are controlled and what is the cause of this variability between individuals. This will help us predict those individuals who are more at risk from the adverse effects of nitrogen-containing drugs and from the toxic effects of chemicals in the diet or the environment. This project will also help us develop methods to increase the levels of these protective enzymes and help reduce the effects of exposure to toxic chemicals.Read moreRead less
Investigating Novel Antibody Drug Conjugates For Treating Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$663,447.00
Summary
Chemotherapy is first-line treatment for advanced lung cancer patients. Most patients inevitably develop chemotherapy resistance. To increase chemotherapy effectiveness, we are developing a new antibody-based approach to target cancer cells that die because of chemotherapy. The antibody is armed with a very potent drug released specifically at the cancer to cause death of surrounding, chemotherapy-resistant cells. Killing these cells may reduce rebound cancer growth and cause an immune reaction.