Original Abstract The global objective of the Personalizing EmerGency/Acute therapeuticS Utilizing Systems biology (PEGASUS) Research Program is to improve drug effectiveness and safety in common acute care conditions. Drug therapy for acute conditions in the emergency department is only effective in 25-60% of cases. There is tremendous opportunity to improve acute therapeutics by implementing precision medicine programs in acute care settings. We will use phenotypic data from our electronic health record and link this data to pharmacogenomic and metabolomic data to discover new mechanisms of drug effectiveness and safety. Ultimately clinical, genomic, and metabolomic data will be integrated into predictive systems biology models to improve therapeutic success in acutely ill patients. The PEGASUS program is supported by the Rocky Mountain Biorepository and the Colorado Center for Personalized Medicine. Through the Maximizing Investigators' Research Award for Early Stage Investigators (MIRA-ESI) funding announcement PEGASUS will focus on common acute care conditions such as nausea, pain, and cardiovascular disease with eventual expansion to more uncommon drug safety conditions such as anaphylaxis and torsades de pointes. We utilize polymorphism in drug metabolizing enzymes, such as CYP2D6, as the hub of our models and use the biologic perturbations present in acute illness to identify new pathways, mechanisms, and genetic variants associated with drug safety and effectiveness in these common conditions. In the future, these models will be tested prospectively. Implementation of this systems biology approach to precision medicine will improve drug effectiveness and safety in acute conditions.
Original Narrative/Public Health Relevance The PEGASUS research program applies precision medicine to improve the effectiveness and safety of drugs administered for common acute conditions. This integrated systems biology approach accounts for individual patient variability thereby improving therapeutic success, minimizing adverse drug events, and decreasing health care costs.
| Saben, Jessica L; Shelton, Shelby K; Hopkinson, Andrew J et al. (2018) The Emergency Medicine Specimen Bank: An Innovative Approach To Biobanking In Acute Care. Acad Emerg Med : |
| Monte, Andrew A; Libby, Anne M (2018) Introduction to the Specific Aims Page of a Grant Proposal. Acad Emerg Med 25:1042-1047 |
| Monte, Andrew A; West, Kelsey; McDaniel, Kyle T et al. (2018) CYP2D6 Genotype Phenotype Discordance Due to Drug-Drug Interaction. Clin Pharmacol Ther 104:933-939 |
| Monte, Andrew A; Sun, Hao; Rapp-Olsson, Anna Malin et al. (2018) The Plasma Concentration of MUC5B Is Associated with Clinical Outcomes in Paraquat-poisoned Patients. Am J Respir Crit Care Med 197:663-665 |
| Flaten, Hania K; Monte, Andrew A (2017) The Pharmacogenomic and Metabolomic Predictors of ACE Inhibitor and Angiotensin II Receptor Blocker Effectiveness and Safety. Cardiovasc Drugs Ther 31:471-482 |
