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Northwestern University Feinberg School of Medicine
Department of Pharmacology

Pharmacogenomics

Pharmacogenomics is the study of how an individual’s genetic makeup impacts drug action. Our faculty scientists investigate the impact of genomic variation on efficacy and toxicity of cardiovascular drugs, antidepressants and immunosuppressants in an effort to promote precision medicine. A special emphasis on pharmacogenomics in minority populations offers opportunities to make genomic medicine more inclusive and impactful.

Our Work

Pharmacogenomics in African-Americans

Pharmacogenomics in African-Americans and Other Understudied Populations

Minoli Perera, PharmD, PhD, associate professor of Pharmacology, studies African American pharmacogenomics, which is the study of an individual’s genome to predict how they will respond to drugs.

Investigating the Pharmacogenomics of Chemotherapy Toxicity

Paul Burridge, PhD, associate professor of Pharmacology, studies how a patient’s genetics cause negative responses such as cardiotoxicity to chemotherapy agents.

Pharmacogenomics of Chemotherapy Toxicity
Investigating Why Mutations in Ion Channels Cause Disease

Investigating Why Mutations in Ion Channels Cause Disease

Paul DeCaen, PhD, associate professor of Pharmacology, studies why a class of proteins called ion channels cause diseases. His goal is to intervene with these diseases and either keep them from happening, or perhaps, control them after they've already manifested.

Pharmacogenomics Research Labs

 Paul Burridge Lab

Investigating the application of human induced pluripotent stem cells to study the pharmacogenomics of chemotherapy off-target toxicity and efficacy

Research Description

The Burridge Lab team poses for a photo
The Burridge Lab team poses for a photo

The Burridge Lab studies the role of the genome in influencing drug responses, known as pharmacogenomics or personalized medicine. Our major model is human induced pluripotent stem cells (hiPSC), generated from patient's blood or skin. We use a combination of next generation sequencing, automation and robotics, high-throughput drug screening, high-content imaging, tissue engineering, electrophysiological and physiological testing to better understand the mechanisms of drug response and action.

Our major effort has been related to patient-specific responses to chemotherapy agents. We ask the question: what is the genetic reason why some patients have a minimal side effects to their cancer treatment, whilst others have encounter highly detrimental side-effects? These side-effects  can include cardiomyopathy (heart failure or arrhythmias), peripheral neuropathy or hepatotoxicity (liver failure). It is our aim to add to risk-based screening by functionally validating genetic changes that predispose a patient to a specific drug response.

Recent Findings

  • Human induced pluripotent stem cells predict breast cancer patients’ predilection to doxorubicin-induced cardiotoxicity
  • Chemically defined generation of human cardiomyocytes

Current Projects

  • Modeling the role of the genome in doxorubicin-induced cardiotoxicity using hiPSC
  • Investigating the pharmacogenomics of tyrosine kinase inhibitor cardiotoxicity
  • hiPSC reprogramming, culture and differentiation techniques
  • High-throughput and high-content methodologies in hiPSC-based screening

For lab information and more, see Dr. Burridge’s faculty profile and lab website.

Publications

See Dr. Burridge's publications on PubMed.

Contact

Contact Dr. Burridge at 312-503-4895.

 Al George Lab

Investigating the structure, function, pharmacology and molecular genetics of ion channels and channelopathies

Research Description

An inside look at the George Lab
An inside look at the George Lab

Ion channels are ubiquitous membrane proteins that serve a variety of important physiological functions, provide targets for many types of pharmacological agents and are encoded by genes that can be the basis for inherited diseases affecting the heart, skeletal muscle and nervous system.

Dr. George's research program is focused on the structure, function, pharmacology and molecular genetics of ion channels. He is an internationally recognized leader in the field of channelopathies based on his important discoveries on inherited muscle disorders (periodic paralysis, myotonia), inherited cardiac arrhythmias (congenital long-QT syndrome) and genetic epilepsies. Dr. George’s laboratory was first to determine the functional consequences of a human cardiac sodium channel mutation associated with an inherited cardiac arrhythmia. His group has elucidated the functional and molecular consequences of several brain sodium channel mutations that cause various familial epilepsies and an inherited form of migraine. These finding have motivated pharmacological studies designed to find compounds that suppress aberrant functional behaviors caused by mutations.

Recent Findings

  • Discovery of novel, de novo mutations in human calmodulin genes responsible for early onset, life threatening cardiac arrhythmias in infants and elucidation of the biochemical and physiological consequences of the mutations.
  • Demonstration that a novel sodium channel blocker capable of preferential inhibition of persistent sodium current has potent antiepileptic effects.
  • Elucidation of the biophysical mechanism responsible for G-protein activation of a human voltage-gated sodium channel (NaV1.9) involved in pain perception.

Current Projects

  • Investigating the functional and physiological consequences of human voltage-gated sodium channel mutations responsible for either congenital cardiac arrhythmias or epilepsy.
  • Evaluating the efficacy and pharmacology of novel sodium channel blockers in mouse models of human genetic epilepsies.
  • Implementing high throughput technologies for studying genetic variability in drug metabolism.
  • Implementing automated electrophysiology as a screening platform for ion channels.

For lab information and more, see Dr. George’s faculty profile.

Publications

See Dr. George's publications on PubMed.

Contact

Contact Dr. George at 312-503-4892.

 Zhe Ji Lab

Dissecting the regulation of gene transcription and RNA translation underlying oncogenic processes

Research Description

Cancer happens through accumulated genetic mutations and epigenetic alternation in normal cells. With the advances of genomic technologies, we now can precisely characterize the genome-wide alternations of gene expression underlying oncogenic processes in a cost-effective and unbiased manner. My lab will use the combined experimental genomic technologies and computational modeling to examine the regulation of gene transcription and RNA translation during steps of oncogenesis. We aim at revealing novel cancer therapeutic targets and strategies for precision medicine and immunotherapy.

Current Projects

Currently, we are working on the following projects.

  • Characterizing the transcriptional regulatory circuits mediating inflammation in the cancer microenvironment.
  • Examining the genome-wide regulation of RNA translation in cancers.
  • Defining the functional roles of non-canonical translation in lncRNAs, pseudogenes and 5’UTRs in cancers.

For lab information and more, see Dr. Ji's faculty profile.

Publications

See Dr. Ji's publications on PubMed.

Contact

Contact Dr. Ji at 312-503-2187.

 Minoli Perera Lab

Pharmacogenomics research in minority patient populations

Research Description

The Perera laboratory focuses on pharmacogenomics (using a patient's genome to predict drug response) in minority populations. Working in this translation research space requires both clinical expertise as well as the use of high-throughput basic science approaches. Our goal is to bring the benefits of precision medicine to all US populations.

The Perera lab has recruited patient populations from around the world. The data collection includes genomic (DNA), transcriptomic (mRNA), pharmacokinetic and clinical data. We then integrate these different data sources to understand genetic drivers of drug response (e.g. genetic predictors of adverse events) as well as disease. By studying minority populations the lab has discovered genetic risk variants that may benefit the implementation of precision medicine in African Americans and others.

Recent Findings

  • Warfarin Bleeding Risk Association study: We recently discovered a genetic variant that predispose African Americans to bleeding complications while on anticoagulant drugs. These bleeds occurred even when the patient was within the therapeutic window for the medication. We hope that this new data will help to identify high risk individuals prior to therapy.
  • Novel African-specific genetic polymorphisms predict the risk of venous thromboembolism: We discovered a new genetic variant associated with a 2.5 fold increase in risk of developing a blood clot. We went on to show that this SNP significantly affects the expression of a key protein in the coagulation cascade. View article on PubMed.
  • Common genetic variant is predictive of warfarin metabolism and gene expression in African Americans: We tested the association of a SNP, previously shown to effect gene expression CYP2C9, for association with warfarin drug clearance (pharmacokinetics). This SNP increased the expression of CYP2C9 (enzyme that metabolized warfarin), hence causing fast clearance of the drug. This African American-specific SNP may help to explain the higher warfarin dose required by African Americans in general. View article on PubMed.

Current Projects

  • Genomics of Drug Metabolism: We are using African America primary hepatocytes to understand the genetic regulation of drug metabolizing enzymes that are involved in a majority of drug used in the US.
  • Anticoagulant Pharmacogenomics: We are conducting several genetic association studies to understand both the genetic drivers and the biological mechanisms behind response and adverse effect to anticoagulant medications.
  • Pharmacogenomics of Inflammatory Bowel disease: We are investigating the genetic predictors of primary non-response to biologic therapies used in inflammatory bowel disease. Studies have implication for other autoimmune disorders that target the same pathways.
  • eMERGE: We are involved in analyzing the GWAS and sequencing data specifically for genomics variation affect key pharmacogenomics gene in African Americans.

For lab information and more, see Dr. Perera's faculty profile and lab website.

Publications

See Dr. Perera's publications on PubMed.

Contact

Contact Dr. Perera at 312-503-6188 or the lab at 312-503-4119.