29595 - Pharmacogenomics

Learning outcomes

By the end of the course, the student understands how to correlate gene expression or single-nucleotide polymorphisms with pharmacokinetics and pharmacodynamics, as well as drug receptor target effects, in order to explore the influence of acquired and inherited genetic variation on drug response in patients.

Course contents

Module 1

• General concepts of pharmacology (pharmacokinetics and pharmacodynamics)
• Pharmacogenetics and Pharmacogenomics: introduction and general concepts (SNPs, SNPs and ADRs, genomic biomarkers, pharmacogenetics and pharmacogenomics, PharmgKB)

• Pharmacogenetics and Pharmacogenomics and drug response (Ultra and poor metabolizers, SNPs that affect drug response - TPMT; CYP450; NAT2; UGT; HLA-B*5701)
• Gender differences in pharmacology
• Pharmacogenetics and Pharmacogenomics in cancer
• Germline genome and PGx
• Pharmacogenetics in cardiovascular diseases
• Age and drug response
• Ethnicity and race in drug response
• Epigenetics (in particular miRNAs; Epigenetics and Cancer: role of miRNAs)
• Liquid biopsy

Module 2.

Introduction to pharmacoepigenomics: general aspects;

-Interactions between genome and environment in the modulation of the pharmacological response;

-Interactions between genome and environment in the modulation of side effects.

Pharmacoepigenomics deals with:

- the influence that epigenetic alterations (DNA methylation, histone modifications, chromatin remodeling, non-coding RNA dysregulation) exert on drug efficacy and safety; -the influence of the effects that drugs may have on the epigenetic machinery;

-Genes involved in pharmacogenomics are also affected by epigenetic modifications conditioning the therapeutic outcome;

-Drugs may modify epigenetic functions under normal and pathological conditions.

- Epigenetic drugs with potential effects in CNS disorders;

How epigenetic phenomena affect drug response in CNS diseases: addiction, chronic pain, neurodegenerative diseases, neuropsychiatric diseases.

-Epigenetic drugs: DNA methyltransferase inhibitors, histone deacetylase inhibitors, histone acetyltransferase modulators, histone methyltransferase inhibitors, histone demethylase inhibitors, non-coding RNAs (miRNAs).

-Ubiquitin proteasome system and interactions with epigenetic modifications.

–Animal models of human diseases.

 

Readings/Bibliography

Scientific literature

Teaching methods

Lectures and seminars.

Frontal lessons useful for both students and teacher in explaining.

Students can interact with the Teacher to ask questions.

Assessment methods

The exam will consist in two oral tests aimed at assessing the student's understanding and knowledge of the topics set out during the course.

The examination of the modules 1 and 2 consists of an interview; the two modules can be given separately.

The marks obtained for each module, in proportion to the number of credits, contribute to the final grade of thirty.

Teaching tools

PC, websites.

Office hours

See the website of Patrizia Romualdi

See the website of Gloria Ravegnini