About Our Lab
The Burridge lab works in the field of pharmacogenomics and precision medicine, using human induced pluripotent stem cells (hiPSC) to study the role of the genome in drug response and complex disease traits. We aim to develop next generation tools for predicting which patients will experience adverse drug responses, validate the causal role of particular single nucleotide polymorphisms (SNPs), probe the mechanisms of action, and discover new drugs to overcome these complications. It is our ambition to translate these techniques to the clinic, to improve personalized patient care and drug efficacy, and to eliminate off-target toxicity.
Our major effort has been focused on SNPs involved in patient-specific chemotherapy-induced toxicity, particularly in breast cancer and pediatric cancer patients who experience cardiotoxicity because of their chemotherapy, some of whom then suffer heart failure requiring heart transplant. We ask the question: what is the genetic reason why some patients experience minimal side effects of their cancer treatments, whilst others encounter highly detrimental side effects? These side effects can include heart failure or arrhythmias, atherosclerosis, nerve damage, liver failure, or infertility. Our work has contributed to risk-based screening by functionally validating genetic changes that predispose a patient to a specific drug response.
The hiPSC we use are generated from less than a teaspoon of patients’ blood and have the potential to become any cell type in the body. We have worked to improve the methodologies for hiPSC generation, along with cardiac, endothelial, hepatocyte, and hematopoietic differentiation, using developmental biology paradigms. We are now continuing to develop protocols to enable us to utilize these cells to model individual patients’ phenotypes.
Once we have discovered a genetic variant correlated to a specific drug response, we probe the underlying mechanisms of action, performing CRISPR-based genome editing and genome-wide CRISPR-knockout screens. We then perform insight-driven drug screens or screening of large drug compound libraries to discover new drugs that can minimize adverse drug responses.
In addition to this work we have developed programs in cardiovascular regenerative medicine, repairing the heart after heart attack or ameliorating the effects of heart failure, and studying how heritable (germline) variation influences cancer drug efficacy.