PHRM 580 Topics in Pharmacogenetics

Course Director: Alexander Steven Whitehead, DPhil; Department of Pharmacology

10am-12pm, Fridays in M100, John Morgan Building

This is a “literature-based” course (i.e. a seminar course/literature survey). It will survey the emerging technologies and computational advances that have permitted the field of Pharmacogenetics to mature into a major biomedical discipline over the past few years. It will consider the likely impact on disease target identification; the development of new drugs for established and “niche” markets; the advent of “personalized medicine” including the selection of therapies that have maximum efficacy and minimum side-effect profiles. This course will also touch on some of the ethical issues associated with the routine genetic testing of patients to facilitate treatment choices and clinical monitoring.

Proposed Sessions:

Each session will last for two hours (between 10am and 12 on Friday mornings) and will be moderated by a faculty member. Each session will consider key original papers, reviews and, on occasion, articles from the popular press. The students participating in the course will make presentations of the relevant material that are followed by group discussion. Some (but not all) sessions will require the faculty member to make a short “mini-lecture” to introduce the broad aspects of the topic under consideration. Students will be evaluated based on both discussion (including presentation) and a short paper dealing with one of the course topics other than one that they have been responsible for presenting to their peers. Evaluation will be heavily loaded towards discussion (and presentation).

The course director will make every effort to attend each session.

Jan 12th - Course overview and introduction to pharmacogenetics. (Whitehead)

Jan 19th - Biostatistical approaches to the analysis of genotype and phenotype data in
pharmacogenetic studies and clinical trials. (Sean Hennessey, Pharm.D., Ph.D.)

Jan 26th - Ethical issues posed by the application of Pharmacogenetics. This session will include an in-depth critique of the controversy around the research activities of Decode Inc., the Iceland-based genomics company. (Pamela Sankar, Ph.D.)

Feb 2nd - Gene expression profiling as a tool for the discovery of pathogenic pathways,

candidate genes for disease association and pharmacogenetic studies, and the impact of drugs on cellular phenotype. (Jim Eberwine, Ph.D.)

Feb 9th – Genetic factors influencing the maintenance of patients on Warfarin therapy within an acceptable therapeutic window of coagulation. (Stephen Kimmel, M.D.)

Feb 16th – Thiopurine S-methyltransferase deficiency and life-threatening azathioprine and 6-mercaptopurine toxicity. (Whitehead)

Feb 23rd - Modern methods for high throughput genotyping – essential tools for supporting large-scale pharmacogenetic studies. (Don Baldwin, Ph.D.)

March 2nd - Pharmacogenetics of ABC transporters. (Richard Aplenc, M.D.) 

March 9th - Spring break so no class

March 16th - Dihydropyrimidine dehydrogenase deficiency and its impact on cancer chemotherapy using fluorinated pyrimidines. (Whitehead)

March 23rd - Polymorphism in the folate/homocysteine metabolic pathway: predictors of drug efficacy, drug toxicity and elevated risk of co-morbidity, Part I (Whitehead)

March 30th - Polymorphism in the folate/homocysteine metabolic pathway: predictors of drug efficacy, drug toxicity and elevated risk of co-morbidity, Part II (Whitehead)

April 6th - The use of proteomics in genetic and pharmacogenetic studies (Ian Blair, Ph.D.)

April 13th - The cytochrome P450s. Pharmacogenetic lessons learned from the archetypal pharmacogenetically-relevant multigene family. (Whitehead)