PHAR 6224 Pharmacogenomics: Genetic Basis for Variability in Drug Response Spring 2015 2 Credits Thursday 230-425pm, Moos Tower 1-450, 302 Heller Hall Course Director: Course Faculty: Pamala Jacobson, PharmD Professor Office Address: Experimental and Clinical Pharmacology WDH 7-151 email: jacob117@umn.edu Phone: 612-624-6118 William S Oetting, PhD, Professor Office Address: Experimental and Clinical Pharmacology 14-255 Moos Tower 515 Delaware St SE email: oetti001@umn.edu Phone: 612-624-1139 Robert Straka, Pharm.D, Professor Office Address: Experimental and Clinical Pharmacology WDH 7-117 Minneapolis, MN Email: strak001@umn.edu Phone: 612-625-5663 Jeff Bishop, PharmD, Associate Professor Office Address: Experimental and Clinical Pharmacology 14-271 Moos Tower Email: jrbishop@umn.edu Phone: 612-625-5435 Jacob Brown, PharmD, Assistant Professor Office Address: Pharmacy Practice and Pharmaceutical Sciences 115 Life Sciences, 1110 Kirby Drive Duluth, MN, 55812 Email: jtbrown@d.umn.edu Phone: 218-726-6028
Brian VanNess, PhD, Professor Office Address: College of Biological Sciences and Institute of Human Genetics 14-287 Moos Tower 515 Delaware St SE Email: vanne001@umn.edu Phone: 612-624-9944 Michael Walters, Ph.D, Research Associate Professor Institute for Therapeutics Discovery & Development 717 Delaware St SE, Room 609 email: walte294@umn.edu Phone: 612-626-6864 Kinjal Sanghavi, Senior Graduate student Office Address: Experimental and Clinical Pharmacology 308 Harvard St SE Minneapolis, MN Email: sangh018@umn.edu Phone: 612-624-9683 Teaching Assistants: Duluth Wilson Lau, PharmD student Email: lauxx245@d.umn.edu Twin Cities To be determined as needed from the TC TA pool Rooms: Twin cities MT 1450/Duluth HH 302 Course Description: Meeting Time: Thursday 230-425pm Phar 6224 is a 2 credit elective course oriented towards 3 rd year pharmacy and graduate students. This course consists of lectures and in class discussions designed to introduce the theory and practice of pharmacogenomics. The goal of the course is to give students an understanding of the principles of human genetics and genomics as they apply to improving the problems in drug therapy optimization and patient care. The genetic basis of variability in drug response can contribute to drug efficacy and toxicity, adverse drug reactions and drug-drug interactions. As such, pharmacists need an understanding of the genetic component of patient variability to deliver effective
individualized pharmaceutical care. Understanding of the basics of pharmacogenomics will enable students to better understand and manage the new genomics based tools as they become available as well as make best treatment choices. The principles covered in this course will prepare pharmacists and clinical scientists to critically evaluate, interpret and apply this information. Learning Objectives: Textbook: Prerequisites: At the conclusion of the course, the student will be able to: 1. Explain the basic principles of human genetics and heredity as they apply to inter-individual variation in treatment response. 2. Apply the principles of molecular and cellular biology to explain the genetic basis of variability in drug response. 3. Describe the various biochemical/molecular biology methods used to determine genotype and polymorphic variability. 4. Discuss how genetic variability in genes encoding drug metabolizing enzymes, drug transporting proteins, and drug receptors (targets) can contribute to variability in drug disposition and action, leading to changes in pharmacokinetics, pharmacodynamics and clinical outcome. 5. Recognize the societal and ethical implications of genetic testing and the resultant individualization of drug therapy. 6. Apply pharmacogenomic concepts to a particular drug therapy to solve relevant problems in pharmaceutical care. 7. Critically evaluate the current and future literature in the area of pharmacogenomics. 8. Identify key sources and reliable data-bases with pharmacogenomics knowledge base. Pharmacogenomics: An Introduction and Clinical Perspective; Joseph S. Bertino and Angela Kashuba. 2012 (Optional) College of Pharmacy professional student in Duluth or Twin Cities in the third year of the Pharm.D. program, Experimental and Clinical Pharmacology graduate students and others with permission.
Course Format: Exams and assignments: Grading Policy: Class format will be traditional lecture/discussion or seminar format, in class discussion of assigned readings, hands on activities using databases and clinical case studies where the discussion in based around a situation (problem) that a pharmacist may encounter that requires application of the knowledge of genetic variability and drug response There will be one midterm exam during the semester. This exam will be worth 30 points. The final exam will be comprehensive, i.e., it will cover material from the entire semester and will be worth 30 points. There will also be a series of class assignments/homework (20 points) and two quizzes (10 points each). Exams and quizzes will be given in class. Students who have questions regarding the grading of the midterm exam or quizzes must submit them in writing to the instructor within one week following the return of the exam or quiz grades. Grades will be assigned for Phar 6224 according to the following: Grade %Range Grade %Range Grade % Range A 93-100 B- 80-82 D 60-69 A- 90-92 C+ 77-79 F Less than 60 B+ 87-89 C 73-76 B 83-86 C- 70-72 Honor Code: Make-Up Policy: Each students is bound by the following specific provisions as part of the honor code: Academic misconduct is any unauthorized act which may give a student an unfair advantage over other students, including but not limited to: falsification, plagiarism, misuse of test materials, receiving unauthorized assistance and giving unauthorized assistance. Specifically, each student will be required to do her/ his own work on all assessments unless otherwise stated. A make up assignment or exam may be allowed only under one of the following circumstances: illness, verified by a note from a medical doctor; a family emergency, verified by note from the professional person in attendance; a university of Minnesota- sponsored event, verified by a note from the leader of the sponsoring organization.
Disability Accommodations: The University of Minnesota is committed to providing all students equal access to learning opportunities. Disability Services is the campus office that works with students who have disabilities to provide and/or arrange reasonable accommodations. Students registered with Disability Services, who have a letter requesting accommodations, are encouraged to contact the instructor early in the semester. Students who have, or think they may have, a disability (e.g. psychiatric, attentional, learning, vision, hearing, physical, or systemic), are invited to contact Disability Services. All information will be kept confidential. Minneapolis Campus Duluth Campus Disability Services Disability Services McNamara Alumni Center 256 Kirby Student Center 200 Oak St SE Suite 180 1120 Kirby Drive Duluth, MN 55812 612-626-1333 218-726-8217 www.ds.umn.edu/students/ www.d.umn.edu/access/ Course evaluation: A final summative evaluation of the course and faculty will be conducted during the last week of regularly scheduled classes. Course Schedule Dates Topic Instructor Lecture Hrs In/out class 1/22/15 Introduction Oetting/Jacobson 1 1/1 General information about the course and grading strategy. Introduction to basics principles of human genetics/genomics and drug therapy. Introduction to human genome, evolving concepts of genes/locus. 1/22/15 Molecular biology review Oetting 2 1/1 Basic principles and paradigms of molecular biology (DNA RNA Protein) information on gene promoters, mirna, identification of targets, splicing/alternate splicing. 1/29/15 Genetic variation Oetting 3 1/1 Introduction to genetic variation, types of variants, SNPs, coding and cis/trans regulatory variants, insertion/deletions, copy number variants, next gen sequencing 1/29/15 Genetic variation Oetting 4 1/1 SNPs, allele nomenclature (rs#, *#), national pharmacogenetics resources/efforts (PGRN), population/allele frequency distribution
2/5/15 Overview of approaches to conduct and design pharmacogenomic studies (GWAS v. Candidate Genes) Oetting 5 1/1 Importance in pharmacogenomics, how these methods are used in research. How to interpret results 2/5/15 Pharmacogenomics of Adverse Drug Reactions Jacobson 6 1/1 SNP predictors of serious toxicities 2/12/15 Influence of pharmacogenomics on drug pharmacokinetics and pharmacodynamics Variants that influence systemic exposure (enzymes and transporters) or pharmacodynamic effects Jacobson 7 1/4 2/12/15 In class Quiz Jacobson/Oetting 8 1/1 Covers lectures 1-6 2/19/15 Hands on exercise with genomics databases Sanghavi 9 1/1 PharmGKB, NCBI, 1000genomes, hapmap, etc 2/19/15 Pediatric Pharmacogenomics (ADHD, PPI, Brown 10 1/1 codeine, asthma) Part 1 Variants affecting common drugs used in children and special considerations of genetics in this population 2/26/15 Pediatric Pharmacogenomics. Part 2 Brown 11 1/1 Variants affecting common drugs used in children and special considerations of genetics in this population 2/26/15 Pharmacogenomics in Cardiology. Part 1 Straka 12 1/1 Variants affecting drugs used for cardiovascular indications such as HTN, hyperlipidemia 3/5/15 Pharmacogenomics in Cardiology. Part 2 Straka 13 1/1 Variants affecting drugs used for cardiovascular indications such as HTN, hyperlipidemia 3/5/15 Clinical consequences of pharmacogenomics Straka 14 1/1 based drug interactions The impact of how genetic variants modify the severity of a drug interaction 3/12/15 Pharmacogenomics in Psychiatry Bishop 15 1/1 Variants affecting drugs used for psychiatric indications 3/12/15 Pharmacogenomics in Psychiatry Bishop 16 1/1 Variants affecting drugs used for psychiatric indications
3/19/15 Oncology Part 1 VanNess 17 1/1 Genetic variation in tumors and how they affect response or toxicity to anticancer and targeted cancer agents 3/19/15 Oncology Part 2 VanNess 18 1/1 Genetic variation in tumors and how they affect response or toxicity to anticancer and targeted cancer agents 3/26/15 In Class Midterm Test. Covers lectures 7-16 Jacobson 19-20 1/6 Spring Break: March 27-April 3 4/9/15 Warfarin, immune suppressants and hepatitis C Jacobson 21 1/1 Pharmacogenomics Case studies/discussion. Part 1 The influence of genetic variants on warfarin efficacy and toxicity, tacrolimus pharmacokinetics and viral genotype on selection of hepatitis C therapy 4/9/15 Warfarin, immune suppressants and hepatitis C Jacobson 22 1/1 Pharmacogenomics Case studies/discussion. Part 2 The influence of genetic variants on warfarin efficacy and toxicity, tacrolimus pharmacokinetics and viral genotype on selection of hepatitis C therapy 4/16/15 Drug development in the post-genomic era Walters 23 1/1 Use of genetics in development of new therapies in pharmaceutical industry 4/16/15 In class quiz Covers lectures 21-23 Jacobson 24 1/1 4/23/15 Ethical, social and legal issues Van Ness 25 1/1 Equity of access, cost of treatments and genetics, possible adverse consequences of knowledge of risk alleles, duties to warn, returning genetic results to patients 4/23/15 Ethical, social and legal issues case examples Van Ness 26 1/3 Equity of access, cost of treatments and genetics, possible adverse consequences of knowledge of risk alleles, duties to warn, returning genetic results to patients 4/30/15 PGx commercialization, PGx cases and interpretation of genetic data Bishop/Brown 27 1/3
4/30/15 Final exam review All faculty 28 1/1 5/7/14 In Class Final Exam (comprehensive ) All faculty 29-30 1/8 Revised 10/28/14 Revised 11/11/14 Revised 12/15/14 Revised 12/19/14 Revised 1/5/15 with classroom Revised 1/9/15 with updated spring break schedule