Novel Cellular Trafficking Mechanisms For The Drug Influx Transporter, Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in indivi ....Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in individuals.Read moreRead less
TIR Signalling Pathway Pharmacogenomics And Opioid Response: Beyond The Mu Opioid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$246,396.00
Summary
This project will identify why some people respond poorly and others have toxic side effects to the major group of pain relieving medications, the opioids. The basis will be the genetics of the immune system and both acute postoperative and chronic cancer pain patients will be studied in this international pharmacogenetics project.
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.
Pharmacogenomics And Mechanistic Basis Of Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$677,220.00
Summary
Drug allergy causes physical harm, anxiety and may limit treatment options. We introduced personalised genetic testing to prevent one such drug hypersensitivity. Genetic information from patients who have had adverse drug reactions will be used to work out how drugs trigger severe allergic reactions and develop strategies to predict these reactions and design safer drugs. This research has relevance to our understanding of other inflammatory disease such as autoimmune disease and multiple sclero ....Drug allergy causes physical harm, anxiety and may limit treatment options. We introduced personalised genetic testing to prevent one such drug hypersensitivity. Genetic information from patients who have had adverse drug reactions will be used to work out how drugs trigger severe allergic reactions and develop strategies to predict these reactions and design safer drugs. This research has relevance to our understanding of other inflammatory disease such as autoimmune disease and multiple sclerosis.Read moreRead less
Medicines are not effective in all people and harmful effects from normal doses can cause suffering and even death. Ethnicity due to genetic factors can cause some medicines to be ineffective or toxic. There is little knowledge on drug genetics of Aboriginal people in contrast to Caucasians. We will study all the major drug genetic factors in groups of Aboriginal people and compare this to other ethnicities to inform physicians as to the optimal drug and dose to prescribe Aboriginal people.