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.
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.
PHARMACOGENETICS OF ANTIDEPRESSANT RESPONSE AND REMISSION: TOWARD GENOTYPE-GUIDED PRESCRIBING IN MAJOR DEPRESSIVE DISORDER
Funder
National Health and Medical Research Council
Funding Amount
$435,524.00
Summary
A “one-size fits all” approach to antidepressant pharmacotherapy in depression is suboptimal. Current technology and scientific data support the transition to a personalised approach to antidepressant pharmacotherapy. My research will (1) develop and test genetic based algorithms for their ability to predict antidepressant response and remission and (2) evaluate the clinical validity and utility of currently available algorithms in clinical practice.
Rapid point-of-care detection of genomic variations for personalised medicine. Selecting treatment based on a person’s genetic profile can improve drug safety and efficacy, but the application is hampered by the inconvenience, slow result turnaround and high cost of current lab-based tests. Full implementation of personalised medicine in clinical practice requires a point-of-care testing system. This project aims to overcome the challenges involved in developing such a system by validating novel ....Rapid point-of-care detection of genomic variations for personalised medicine. Selecting treatment based on a person’s genetic profile can improve drug safety and efficacy, but the application is hampered by the inconvenience, slow result turnaround and high cost of current lab-based tests. Full implementation of personalised medicine in clinical practice requires a point-of-care testing system. This project aims to overcome the challenges involved in developing such a system by validating novel rapid genotyping methods and developing ultrasensitive real-time DNA detection that will be integrated on a single chip platform to facilitate a small, low cost and reliable test device. The technology will be readily adaptable to areas where prompt access to genomic information is valuable, such as disease diagnosis and risk prediction.Read moreRead less
Can Decision Analytic Modelling Promote Clinical Translation Of Personalised Medicine Markers For Oncology Drugs?
Funder
National Health and Medical Research Council
Funding Amount
$69,893.00
Summary
Personalised medicine is an approach that has great potential to improve healthcare. There has been limited success to date, however, in utilising proposed tests in the clinical. It is proposed that use of mathematical models early in the development of personalised medicine tests will allow early understanding of the value that the test will have for patients and society. Such insight will help build a strong case to undertake the research required before personalised medicine can be more widel ....Personalised medicine is an approach that has great potential to improve healthcare. There has been limited success to date, however, in utilising proposed tests in the clinical. It is proposed that use of mathematical models early in the development of personalised medicine tests will allow early understanding of the value that the test will have for patients and society. Such insight will help build a strong case to undertake the research required before personalised medicine can be more widely used to improve treatment for cancer.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.
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