Mary Barber

Mary Barber

PI: Javid Moslehi, MD, Department of Cardiovascular Medicine, Cardio-Oncology Program

From Bench to Bedside: Modeling Cancer Therapy-Induced Cardiotoxicity in Human Cardiomyocytes

The explosion of novel, targeted and effective cancer therapies has heralded a new era in cancer treatment and introduced survivorship as a new theme in oncology. Both traditional chemotherapies and newer targeted therapies, however, cause cardiotoxicities. These toxicities impede drug development and drug use once approved for treatment. Traditional therapies such as anthracyclines and newer therapies such as HER2 inhibitors (e.g. trastuzumab) and MEK inhibitors (e.g. trametinib) cause cardiomyopathy, or heart failure. Our lab is developing various models that recapitulate cardiotoxicities to both screen new cancer therapies for clinical use and to understand the mechanism of cardiomyopathy caused by existing cancer treatments. My project in the lab has been developing high-throughput means to assess cardiotoxicity of traditional and new cancer therapies. My research uses human induced-pluripotent stem cells differentiated into cardiomyocytes (hiPSC-CM). We adapted a protocol for hiPSC-CM differentiation and maturation developed at Vanderbilt (in the laboratories of Drs. Hong and Knollman) resulting in mature cardiomyocytes in 34 days. After maturation and treatment with cancer therapies, I use a bioluminescent assay to measure cardiomyocyte viability, cytotoxicity, and apoptosis. I have preliminary data on these cardiotoxicity end points in cells treated with doxorubicin, a traditional chemotherapy, and newer targeted therapies including HER2 inhibitors for breast cancer and MEK inhibitors for metastatic melanoma, among others. This model will enable cardiologists, oncologists, and drug developers to assess cardiotoxicities prior to clinical use and will provide insight into the mechanism of heart failure caused by traditional and new cancer therapies.