Pharmacogenomics

Recommended Prerequisites

General knowledge of Biomedicine area (BSc and/or MSc)

Teaching Methods

A “Meet the Expert” session is included to provide the students to interact with international expert scientists.
“Paper Club” discussions are organized for achieving the most relevant and up-to-date findings in current literature and international guidelines.
Students are asked to suggest a guideline for the application of pharmacogenomic assays in the clinical practice, in an “Open discussion” special session.
Form of evaluation: Final Mark= A + B + C

D- Task 1- Presentation of scientific papers – groups of 2-3 students: max 6 val
a. The coordinator distributes papers to be prepared in groups and presented – max 10 min each. The presentation should follow the scheme (maximum 10 slides):

I. Introduction
II. Objectives
III. Methods
IV. Results
V. Conclusions
VI. Critical analysis

The speakers ask questions to the students for discussion.

E- Task 2- Autonomic search and present major guideline based on peer- reviewed papers and/or reference documents/ legislation – one from each student: max 8 val
a. According to the subject in the programme (“Application of pharmacogenomics in the clinical practice and ethic issues associated”), the students should prepare a ppt slide with one guideline that should be followed. The reference(s), in which the guideline was(were) based on, has(have) to be also included. The slide and pdf of paper(s) have to be sent to the coordinator by email until the end of day 3 (7:00 p.m.) during the course, with the identification of the student (name of the file “name_task2 PhCGx2013”).
b. The guidelines will be presented at the OPEN DISCUSSION Session, day 5 (~1:30 p.m.).

F- Task 3- Delineate 2 questions based on given papers and discuss with the experts – groups  of 2-3 students: max 6 val

a. According to the paper (published by the Expert team) sent previously by the Coordinator to the group, the students are asked to prepare a ppt slide with 2 questions. The reference, in which the questions were based on, has to be also included. The slide has to be sent to the coordinator by email until the end of day 4 (7:00 p.m.) during the course, with the identification of the students and group number (name of the file “groupN_task3 PhCGx2013”).
The questions will be presented at the MEET THE EXPERT Session, day 5 (~5:00 p.m.)

Learning Outcomes

This course is directed to students aiming to know and understand the basic concepts and clinical applications of Pharmacogenomics.

The course will teach the basic principles of Biochemical Genetics underlying the variability in response to therapeutics, according to the genetic individual profile. Additionally, the most recent developments in pharmacogenomic approach to diseases and epigenetic effects of particular chemicals will be brought to discussion. The knowledge of the mechanisms involved in genetic and epigenetic modification, together with the identification of the genes codifying factors involved in xenobiotic response (including drugs), is essential to understand the relevance of Pharmacogenomics in the development of new therapeutic agents and in the application of more rational therapies.

Work Placement(s)

No

Syllabus

NOTE: THE STARTING LECTURE OF EACH DAY IS SCHEDULLED TO START AT 13.00H. ENDING TIME IS ESTIMATED AT 20.00H. WORKING GROUPS MEET DURING ~1H EACH DAY PRIOR TO 12H.

 

Monday – Day 1

Introduction

Basic concepts in Pharmacogenomics. Genetic variation and susceptibility genes

Manuela Grazina (PhD, FMUC)

Mutational effect and genetic toxicity: implications in Toxicogenomics.

Manuela Grazina (PhD, FMUC)

Mechanisms of DNA repair – Pharmacogenomic issues

Carolino Monteiro (PhD, FFUL)

Papers presentation and discussion I (presentation by students; discussion with speakers)

Manuela Grazina (PhD, FMUC); Carolino Monteiro (PhD, FFUL)

Tuesday – Day 2

Pharmacokinetics and pharmacodynamics

Carlos Fontes Ribeiro (MD, PhD, FMUC)

Mechanisms mediating drug metabolism

Manuela Grazina (PhD, FMUC)

Pharmacogenetics of drug receptors

Manuela Grazina (PhD, FMUC)

Nutrigenomics: concepts and applications to Pharmacogenomics and clinical practice Manuela Grazina (PhD, FMUC)

Pharmacogenetics in clinical practice – update on heart disease

Fernando Regateiro (MD, PhD, FMUC, HUC

Case study

(MSc/PhD student, FMUC)

Wednesday – Day 3

Pharmacogenomics of addiction (alcoholism and drugs of abuse)

Manuela Grazina (PhD, FMUC)

Papers presentation and discussion III (presentation by students; discussion with speakers

Manuela Grazina (PhD, FMUC); Catarina R. Oliveira (MD, PhD, FMUC)

Pharmacogenomic glance of Anaesthesia

Teresa Lapa (MD, CHC)

Genetic profile and therapeutic approach to pain

Ana Valentim (MD, HUC)

Targets for pharmacogenetic profiles and therapeutics in clinical practice – time to think science

Manuela Grazina (PhD, FMUC)

Thursday – Day 4

Genes, Pharmacogenetics and cancer

Rui Medeiros (PhD, IPO-Porto)

Papers presentation and discussion II (presentation by students; discussion with speakers       Manuela Grazina (PhD, FMUC); Rui Medeiros (PhD, IPO-Porto)

Genetic profile and therapeutic approach to Alzheimer’s Disease

Isabel Santana (MD, PhD, HUC, FMUC)

Pharmacogenomics and Toxicogenomics – the good, the bad and the ugly

Manuela Grazina (PhD, FMUC)

Friday – Day 5

Ethics and pharmacogenomics: impact in Medicine

OPEN DISCUSSION(students are asked to do autonomic search and bring major guidelines based on peer-reviewed papers- one from each student)

International guidelines for genotoxicity assays of novel therapeutic agents

Carlos Fontes Ribeiro (MD, PhD, FMUC)

Pharmacogenomics and population studies

Adrián Llerena (MD, PhD, FMUE)

Seminar: Pharmacogenomics in the brain: current status and perspectives

POPULATION PHARMACOGENETICS AND ITS IMPLICATION FOR PSYCHOLOGICAL FUNCTIONING AND SUICIDE.

Adrián Llerena (MD, PhD, FMUE) and Eva M Peñas-Lledó (PhD, FMUE)

Meet the expert session(students are asked to delineate questions in groups, based on papers from the experts’ team, and discuss with the experts)

Adrián LLerena (MD, PhD, FMUE) and and Eva M Peñas-Lledó (PhD, FMUE)

Closing remarks

Head Lecturer(s)

Maria Manuela Monteiro Grazina

Assessment Methods

Assessment
Final Mark= A + B + C: 100.0%

Bibliography

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de Mello RA, Marques DS, Medeiros R, Araújo AM. Epidermal growth factor receptor and K-Ras in non-small cell lung cancer-molecular pathways involved and targeted therapies. World J Clin Oncol. 2011 10;2(11):367-76.

Araújo AP, Ribeiro R, Pinto D, Pereira D, Sousa B, Mauricio J, Lopes C, Medeiros R. Epidermal growth factor genetic variation, breast cancer risk, and waiting time to onset of disease. DNA and cell biology 2009;28(5):265-9.

Teixeira AL, Ribeiro R, Morais A, Lobo F, Fraga A, Pina F, Calais-da-Silva FM, Calais-da-Silva FE, Medeiros R. Combined analysis of EGF+61G>A and TGFB1+869T>C functional polymorphisms in the time to androgen independence and prostate cancer susceptibility. Pharmacogenomics J. 2009;9(5):341-6.

Gladding P, Webster M, Zeng I, Farrell H, Stewart J, Ruygrok P, Ormiston J, El-Jack S, Armstrong G, Kay P, Scott D, Gunes A, Dahl ML. The pharmacogenetics and pharmacodynamics of clopidogrel response: an analysis from the PRINC (Plavix Response in Coronary Intervention) trial. JACC Cardiovasc Interv. 2008;1(6):620-7.

Gomez A, Ingelman-Sundberg M. Epigenetic and microRNA-dependent control of cytochrome P450 expression: a gap between DNA and protein. Pharmacogenomics. 2009;10(7):1067-76.

Gupta M, Kaur H, Grover S, Kukreti R. Pharmacogenomics and treatment for dementia induced by Alzheimer's disease. Pharmacogenomics. 2008;9(7):895-903.

Horstmann S, Binder EB. Pharmacogenomics of antidepressant drugs. Pharmacol Ther. 2009 Jun 27. [Epub ahead of print].

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Ooteman W, Naassila M, Koeter MW, Verheul R, Schippers GM, Houchi H, Daoust M, van den Brink W. Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009;14(3):328-37.

Manolopoulos VG, Dechairo B, Huriez A, Kühn A, Llerena A, van Schaik RH, Yeo KT, Ragia G, Siest G. Pharmacogenomics and personalized medicine in clinical practice. Pharmacogenomics. 2011;12(5):597-610

Peñas-Lledó EM, Blasco-Fontecilla H, Dorado P, Vaquero-Lorenzo C, Baca-García E, Llerena A. CYP2D6 and the severity of suicide attempts. Pharmacogenomics. 2012;13(2):179-84.

Peñas-LLedó EM, Dorado P, Pacheco R, González I, LLerena A. Relation between CYP2D6 genotype, personality, neurocognition and overall psychopathology in healthy volunteers. Pharmacogenomics. 2009;10(7):1111-20.

 

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