The research goal of Nadine Norton, Ph.D., is to identify genes and genetic variants that predict which patients will experience pharmacological side effects during cancer treatment and inform appropriate personalized therapeutic intervention. Her research focuses primarily on patients with an aggressive form of breast cancer (HER2-positive) for whom combination chemotherapy and anti-HER2 therapy is potentially lifesaving, but the major clinical side effect is cardiac dysfunction. The long-term goal of Dr. Norton's work is to expand the research to other cancers, to patients with heart failure and to additional clinical side effects such as neuropathy, fatigue and skin toxicities.
- HER2-positive breast cancer. Dr. Norton's team is involved in genomic analyses of germline DNA from several large clinical trials with a view toward identifying the mechanisms, genes and genetic variants that determine therapeutic outcome and pharmacological side effects of ERBB2-targeted therapies.
- Multifocal breast cancer. Dr. Norton's research team uses gene expression profiling and copy number analyses to assess intratumor and intertumor heterogeneity within patients with multiple breast tumors.
- Bioinformatics. Dr. Norton's team is using genome-wide bioinformatics approaches to infer gene expression patterns from germline genetic variants. The novelty of this approach is that gene expression in patients' heart cells will be inferred from genetic data from DNA extracted from peripheral blood.
- Pharmacogenomics. Dr. Norton has a major interest in identifying genes and genetic variants to predict and protect against pharmacological side effects. Her research team routinely uses induced pluripotent stem cell (iPSC)-derived cardiomyocyte models for drug screening.
- Personalized medicine. Dr. Norton has a major research interest in using genomic approaches to understand phenotypic heterogeneity. Her research aims to predict which patients will experience pharmacological side effects and inform appropriate personalized therapeutic intervention.
- Cardiotoxicity. Dr. Norton has a major interest in cancer therapeutic-related cardiotoxicity, including congestive heart failure and asymptomatic decline in left ventricular ejection fraction. Her research uses genomic information from patients in clinical trials and iPSC-derived cardiomyocytes to determine genes and mechanisms of cardiotoxicity and to identify potential therapeutic targets.
- Dilated cardiomyopathy. Dr. Norton has an interest in the identification of genetic variants that cause dilated cardiomyopathy and their frequency in patients who experience cancer therapeutic-related cardiotoxicity.
Significance to patient care
Chemotherapeutic agents and targeted therapies are widely used in the treatment of cancer. As major advances are being made to optimize the therapeutic benefit of these drugs, pharmacological side effects associated with them must also be understood and minimized. Heart failure or decline in heart function is a major side effect in some patients. Dr. Norton's goal is to identify genetic variants that predict which patients will develop heart dysfunction and identify therapeutic targets that will enable these patients to continue to receive lifesaving treatment without heart dysfunction.
- Recipient, Stanley J. Glaser Research Award, University of Miami, 2011