Dan Roden
Principal Investigator
Charles Hong
Co-Investigator
Bjorn Knollmann
Co-Investigator
Tao Yang
Co-Investigator
|
It is a given in clinical medicine that patients vary in their responses to drug therapy: lack of efficacy is common and serious adverse drug reactions (ADRs) remain a leading cause of morbidity and mortality. Several decades of work in pharmacogenomics have illuminated critical genetic pathways contributing to this variability. Prominent successes in the field have identified single common variants with large effect sizes for important drug outcomes, and some of these are now being implemented clinically at our center and elsewhere to increase the likelihood of efficacy or to identify patients at high risk for serious ADRs. However, despite initial application of candidate and unbiased genomic methodologies to large populations, major gaps remain in our understanding of mechanisms of individual variability in drug action. These gaps, in turn, highlight the major unmet needs of modern pharmacogenomic science: to develop robust predictors of drug response in an individual patient prior to embarking on treatment, to develop highly efficient screens to detect ADR liabilities in new drug candidates prior to investment in their development and patent harm, and to exploit an understanding of the molecular basis of drug action to rationally target available drugs.
|
A new paradigm for identifying patients and drugs at risk for QT prolongationThe drug-induced long QT syndrome (diLQTS) continues to be a problem for clinicians balancing risk and benefits across multiple therapeutic areas, and a fundamental issue that this Project will address is the extent to which diLQTS risk is predictable in an individual patient.
|
Understanding and preventing HLA-associated drug reactionsImmunologically mediated adverse drug reactions (IM-ADRs) contribute
disproportionately to drug-related morbidity and mortality and the cost and uncertainty of drug development, and results of these studies will inform strategies for the prediction of severe HLA-associated IM-ADRs and guide drug development and design. |
Precision phenomics to personalize drug therapyThe promise of genomic medicine is the personalization of therapeutics based on one’s genetic makeup, and the results of this study will be to dramatically increase the catalog of genetic predictors of drug response and to create a library of potential repurposing for nearly all medications.
|
Analytical and Administrative Support CoreThe Core is charged with administrative management and with providing centralized data management and analysis functions, and bioinformatics and biostatistics support to the program in order to facilitate progress toward achieving the Center’s short and long term goals.
|