Track 3 - January 24 9.30 A.M.-1.45 P.M.
Pharmacists have long recognized that using unique patient characteristics to guide pharmacotherapy decision-making can improve drug response and mitigate drug-associated risks. Age, weight, and dietary habits were among the first patient-specific characteristics used to individualize pharmacotherapy. As technologies advanced, analytic tools that measure surrogate markers of liver and renal function, together with drug concentrations in biological fluids, were adopted to optimize therapeutic regimens. Cutting-edge genomic technologies are now being integrated into patient care for the selection of targeted therapies and identification of those at increased risk of poor pharmacotherapy outcomes. Precision Pharmacotherapy is combining genetic, environmental, lifestyle, and other unique patient or disease characteristics to guide drug selection and dosage. This session will introduce the concept and give many examples of how precision pharmacotherapy is used in specialties such as pediatrics, psychology, cardiology and oncology to guide prescribing.
Session Chair Profile
Biography
Dr. Relling has been a pioneer in both the science and clinical application of pharmacogenomics. Her research has resulted in seminal laboratory discoveries that unraveled the mechanisms of drug-induced adverse effects, and the integration of biologic, genomic, and pharmacologic discoveries into comprehensive clinical protocols, leading to improved cure rates for children with acute lymphoblastic leukemia. She has led the implementation of clinical protocols for pharmacogenomics at St. Jude Medical as well as their integration into clinical care. In recognition for her work she was elected to the Institute of Medicine (now National Academies of Medicine) in 2009 and also received the Pediatric Oncology Award from ASCO. More recently, Mary has been recognized by the American Society for Clinical Pharmacology and Therapeutics, receiving the Rawls Palmer Progress in Medicine Award. Mary, along with Dr. Teri Klein of Stanford, co-led the formation of the Clinical Pharmacogenomics Implementation Consortium (CPIC) that has published pharmacogenetic guidelines for thirty-five drugs, removing a barrier to pharmacogenetic testing in the clinic. These guidelines are now being implemented around the globe. Mary received her Bachelor of Science degree from the University of Arizona and her PharmD from the University of Utah College of Pharmacy.
Speaker Profile
PharmD, Endowed Chair in Pharmacogenomics, St. Jude Children’s Research Hospital; Professor of Clinical Pharmacy & Pediatrics, University of Tennessee Health Sciences Center
Q&A Interview
Biography
William E. Evans is recognized for his research on the pharmacogenomics of leukemia treatment in children. His lab elucidated the pharmacodynamics of methotrexate treatment of acute lymphoblastic leukemia and discovered the genetic basis for inherited differences in the enzyme thiopurine methyltransferase and defined its role in determining the risk of hematopoietic toxicity in patients treated with mercaptopurine and azathioprine. More recently, his lab has used genomewide strategies to elucidate the importance of both inherited and somatic genome variation in determining the efficacy and toxicity of leukemia chemotherapy. He has been funded by 3 successive NIH MERIT awards and has produced over 400 research publications. He served as CEO of St. Jude Children’s Research Hospital in Memphis TN (USA) from 2004-2014, and was elected into the US National Academy of Medicine in 2002.
Talk
Reversing Drug Resistance in Acute Lymphoblastic Leukemia
This lecture will describe recent strategies to interrogate and integrate multiple types of genetic and epigenetic variation to identify new mechanisms of drug resistance in acute lymphoblastic leukemia (ALL) and reveal novel drug combinations to mitigate resistance. This integrative genomic strategy has the potential to identify new mechanisms of drug resistance in multiple types of human cancers.
Speaker Profile
Ph.D., Professor of Medicine, Indiana University School of Medicine
Biography
Todd Skaar did his graduate work in nutrition at the University of Wisconsin, lactation physiology at the Penn State University, and a postdoc in breast cancer drug resistance at the Lombardi Cancer Center at Georgetown University. Since joining the Division of Clinical Pharmacology at the Indiana University School of Medicine, his research has focused on the discovery and implementation of genomic predictors of drug response. More specifically, his studies are focused on identifying and functionally testing genetic variants in the drug metabolism genes that are associated with clinical drug efficacy and toxicity. They also include studies to identify miRNAs that contribute to the drug-induced and developmental changes in hepatic drug metabolism. He co-leads multiple pharmacogenomics implementation clinical trials focused on identifying and overcoming the barriers to using pharmacogenomics to guide drug therapies. He is also a co-leader of the Cancer Prevention & Control Program of the Indiana University Cancer Center.
Talk
Functional Assay Validation Of Clinical Pharmacogenomic Variants
New variants in clinically actionable pharmacogenomics genes are continually being discovered. Many of these cannot be tested in cohorts of patients because of their low allelic frequency. This talk will discuss multiplexed in vitro assays that can provide functional data to guide the classification of these variants.
Speaker Profile
M.D., Professor of Medicine, Pharmacology, Pathology, Microbiology and Immunology, Vanderbilt University
Biography
At Vanderbilt University Medical Center Dr. Elizabeth Phillips lab studies the development of genetic, molecular and cellular signals to predict and prevent severe life-threatening adverse drug reactions using novel single cell technologies and mass cytometry. She is the John A. Oates Chair in Clinical Research and Director of Personalized Immunology in the Center for Drug Safety and Immunology. She is a physician scientist clinically trained in Infectious diseases and clinical pharmacology who has established new clinical and research programs in drug hypersensitivity, pharmacogenomics and personalized immunology across different healthcare systems. Amongst her greatest translational accomplishments between 2002-2008 she led the development of the HLA-B*57:01 genetic predictor for abacavir hypersensitivity from its discovery through implementation. Important work accomplished since the implementation of HLA-B*57:01 testing has been in elucidating the specific immunopathogenesis of abacavir hypersensitivity and other immunology-mediated drug hypersensitivity syndromes and new genetic discoveries such HLA-A*32:01 and vancomycin-induced drug reaction and eosinophilia and systemic symptoms.
Talk
Using Precision Medicine To Prevent And Understand Severe Immune-Mediated Drug Reactions
Speaker Profile
Ph.D., Division Head – Pharmacogenomics, Sema4
Biography
Dr. Stuart Scott is certified by the American Board of Medical Genetics and Genomics (ABMGG) in Clinical Molecular Genetics and Clinical Cytogenetics, and his research interests include pharmacogenomics, cytogenomics, epigenomics, long-read sequencing, and the implementation of genomic medicine. Dr. Scott is a member of the Clinical Pharmacogenetics Implementation Consortium (CPIC), ClinGen, PharmCAT, PharmVar, International Union of Basic and Clinical Pharmacology (IUPHAR), and other international pharmacogenomics consortia, and has co-authored pharmacogenetic-guided practice guidelines for warfarin, clopidogrel, SSRIs, and voriconazole therapy. He has published over 100 peer-reviewed manuscripts and book chapters on pharmacogenomics, clinical genomics, epigenomics and genomic medicine implementation, and is the co-editor of the 2nd edition of Pharmacogenomics: Challenges and Opportunities in Therapeutic Implementation.
Talk
Translating Pharmacogenomic Variation To Clinical Implementation
This talk will identify currently available resources to support clinical pharmacogenomic testing, with an emphasis on reviewing innovative technologies that interrogate germline variation implicated in drug response variability and translating those test results into clinical practice.
Speaker Profile
PHARMD, Associate Dean for Research and Graduate Education, John Gideon Searle Professor of Translational Pharmacy, University of Michigan College of Pharmacy
Q&A Interview
Biography
Vicki L. Ellingrod, Pharm.D., FCCP is The John Gideon Searle Professor of Clinical and Translational Pharmacy in the Clinical Pharmacy Department in the College of Pharmacy, Professor of Psychiatry and Psychology. She obtained her BS and PharmD from the University of Minnesota and then completed a postdoctoral fellowship in psychopharmacology/pharmacogenetics at the University of Iowa. She then joined their faculty and completed a K08 training grant funded by NIMH (National Institute of Mental Health). In 2006, she joined the University of Michigan. Her research has primarily been funded by the NIMH, FDA, and industry sources and her work focuses on the pharmacogenomics of mental health treatments. Dr. Ellingrod is a founding member of the College of Psychiatric and Neurologic Pharmacists and a full member of the American College of Neuropsychopharmacology (ACNP). She also serves as scientific editor for Pharmacotherapy and is an editor on the DiPiro text book Pharmacotherapy, a pathophysiologic approach.
Talk
Schizophrenia and Folate Pharmacogenomics & Risk for Comorbidities
Schizophrenia comprises 1% of the world’s population, but ranks as a highly costly disease worldwide. Previous work done by our group has focused on the folate hypothesis in schizophrenia and the risk for metabolic complications seen with atypical antipsychotic use. This session will focus on results from our recently completed folate trial, which found cardiovascular and cytokine improve-ments which varied by folate pharmacogenomics. Furthermore, improvement in these clinical outcomes continued 8 weeks after treatment withdrawal for the folate treatment group compared to those receiving placebo (clinicaltrial.gov NCT02074319) which may highlight new precision medicine implications for this work.
Speaker Profile
M.D., Ph.D., Associate Professor of Emergency Medicine & Medical Toxicology, University of Colorado Denver-Anschutz Medical Center
Biography
Dr. Monte’s research focuses on precision medicine and substance abuse. In the precision medicine arena, Dr. Monte aims to improve drug effectiveness and safety in acute care conditions. He links clinical outcomes, available through the electronic health record, to genomic and metabolomic variables in order to generate systems biology models of drug effects with plans to test these algorithms prospectively. As an emergency physician and medical toxicologist, Dr. Monte is well positioned to examine efficacy and safety of drugs and he has the capacity to pair these data with serial biologic samples. Dr. Monte is particularly interested in drug-drug and drug-gene interactions. Dr. Monte’s work in substance abuse examines the public health effects of cannabis liberalization, drug detection, and genomic variability in patient illicit drug responses.
Talk
Pharmacogenetics Of Analgesics
This talk will review the pertinent pharmacogenetics of 3 major drug classes, opioids, NSAIDs, and anesthetics. We will discuss major polymorphic genes such as CYP2D6, CYP2C9, and the opioid receptors and how variants affect common drug effectiveness/safety. We will review the evidence, resources for clinicians, and the holes in knowledge.
Speaker Profile
Ph.D., PharmD, Associate Director, Institute for Precision Medicine, University of Pittsburgh
Biography
Dr. Philip Empey is the Associate Director of the Institute for Precision Medicine at the University of Pittsburgh and UPMC and an Associate Professor in the School of Pharmacy. He directs the Pharmacogenomics Center of Excellence and leads the PreCISE-Rx and Test2Learn teams to implement pharmacogenomics clinical, research, and educational initiatives. As a clinician-scientist, Dr. Empey conducts NIH-funded clinical and translational research aimed at understanding the mechanisms of the variability in drug response to improve medication-related outcomes in critically ill patients. His research interests include large scale population preemptive testing, pharmacogenomics clinical implementation, collection of medication-related phenotype information, genotype-phenotype discovery, and understanding the role/impact of xenobiotic transporters following neurological injury.
Talk
Implementing Pharmacogenomics At Population-Scale
Evidence supports the use of pharmacogenomics to guide prescribing, but barriers to implementation exist. Dr. Empey will present outcomes following CYP2C19 genotyping to guide antiplatelet medication prescribing after cardiac catheterization at Pitt/UPMC and lessons learned from similar programs nationally. Emerging large population-scale preemptive pharmacogenomics initiatives will also be discussed with a focus on contemporary issues in the field.
Speaker Profile
M.D., Cardiologist, Durham Veterans Affairs Medical Center; Associate Professor of Medicine, Center for Applied Genomics & Precision Medicine, Duke University
Biography
His research focuses on the discovery and translation of pharmacogenomic biomarkers to address the hypothesis that tailoring drug therapy on the basis of genomic information can improve health outcomes. He has chosen some of the most commonly used medications used worldwide – antiplatelet and statin medications – for his research. As Director of the VA PHarmacogenomics Action for cancer SuRvivorship(PHASeR) program, he is leading the VA’s implementation of pre-emptive, panel-based, pharmacogenetic testing to up to 250,000 Veterans.
Talk
PHASeR: Implementing Pre-emptive Pharmacogenomic Screening In The Veterans Health Administration
The objective of the VA Pharmacogenomics Action for Cancer Survivorship (PHASeR) program is to provide pre-emptive, panel based, pharmacogenomic screening to up to 250,000 Veterans. I will provide an overview of the strategy to implement pharmacogenetic testing in one of the largest integrated health care systems in the United States.
