Channing Pharmacogenetic and Pharmacogenomic Research

Pharmacogenetics is the study of genetic variation influencing response to drug therapy. The goal of pharmacogenetics is that of personalized, precision medicine that permits safe, effective medication therapy for patients.

Classically, pharmacogenetics can be divided into four categories, with variants influencing aspects of drug availability and action. These categories include pharmacokinetics (including drug absorption, distribution, metabolism, excretion, and transport), pharmacodynamics (interaction of the drug at its primary target), disease modification (whereby disease-related genes also influence response to therapy), and idiosyncratic reactions.

A closely related field to pharmacogenetics is pharmacogenomics, which we also study at the Channing Division of Network Medicine (CDNM). In this context, pharmacogenomics assesses the impact of any genomic variation on drug response. As such, pharmacogenomics also encompasses investigation of variation in drug responses impacted by transcriptomics (mRNA), proteomics (protein), metabolomics (metabolite), and epigenomics (epigenetic changes via DNA methylation, etc.).

Current Research

CDNM investigators have led multiple pharmacogenetic and pharmacogenomic studies affecting both asthma and COPD.

Pharmacogenetics

Pharmacogenetics includes studies of both candidate genes and genome-wide association, including:

• Biologic candidate genes’ underlying response to three major asthma therapeutics: inhaled corticosteroids, bronchodilators, and leukotriene receptor modifiers
• Genome-wide association studies of the three major asthma therapies
• Genetic studies of bronchodilator and oxygen therapy response in COPD
• Interaction and stratified analyses focused on the effect of therapy vs. no therapy, disease severity, and modifications via age, gender, and race

Pharmacogenomics

Pharmacogenomics includes transcriptomic, metabolomic, and epigenomic studies, including:

• Gene expression (via arrays and RNA-sequencing) associations with response to inhaled corticosteroids and leukotriene modifiers
• miRNA in asthma, COPD, and AERD (aspirin exacerbated respiratory disease)
• Cellular pharmacogenomics of inhaled corticosteroids and leukotriene modifiers
• Pharmacometabolomics
• Pharmacoepigenomics (DNA methylation)

Integrative and systems biology studies

• Expression quantitative trait loci (eQTL) pharmacogenomics
• Predictive, personalized testing using Conditional Gaussian Bayesian Networks (CBGN) and LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples)
• PANDA (Passing Attributes between Networks for Data Assimilation) transcriptomic networks
• Drug repurposing in asthma

National and international collaborations

CDNM is a long-standing member of the ongoing NIH Pharmacogenetics Research Network and the Pharmacogenetics in Childhood Asthma (PiCA) consortium.