Dr. Gabrielson's research efforts focus on the signal transduction of cardiovascular toxicities in vitro, in cardiomyocyte culture and in vivo, using rodent models. Specifically, the research focuses on understanding the mechanisms of various cancer therapies that induce cardiac toxicities.
Currently, she is testing prevention strategies for these toxicities. She is studying the cardiac effects of the anthracycline doxorubicin (adriamycin) and the immunotherapeutic agent, Herceptin, anti-erbB2. For patients concurrently treated with Herceptin and doxorubicin, the risk of cardiac dysfunction is 28 percent, compared to 7 percent in doxorubicin alone treatment. She is focusing on the signal transduction pathways in the heart that are modulated by anti-erbB2 treatment, which in turn worsens doxorubicin toxicity. Thus, understanding the mechanisms behind the combined toxicity of doxorubicin and anti-erbB2 will pave the way for the design of strategies to reduce toxicity, identify patients at risk and potentially allow higher levels of this effective combination therapy to be used with an improved long-term survival in patients. In another doxorubicin animal model, she is using the neu mouse model that overexpresses neu (erbB2) and thus develops breast cancer, to test several strategies to prevent doxorubicin toxicity.
For evaluating various cardiac protection strategies, in conjunction with molecular studies, she is also using histopathology, clinical pathology and non-invasive echocardiography in both acute and chronic models of doxorubicin toxicity. Tumor growth and regression is also being monitored during treatment. Some of the pharmacological strategies she is testing have also been shown to reduce tumor burden.
To complement the in vivo studies, toxicity assessments and pharmacological strategies are first screened in vitro in neonatal and adult rat cardiomyocyte cell culture. These projects are funded by a Scientist Development Grant award from the National American Heart Association program, the Department of Defense Breast Cancer Research program and from pilot project funds from the Breast Cancer SPORE and the American Cancer Society.
She is also currently collaborating with multiple investigators within Johns Hopkins University and other universities ranging from cancer research to cardiovascular research.
Technology Expertise Keywords
Toxicology; Pathology; Cancer; Cardiovascular Disease
Wachtman, L, Bedja, D, Pin, S, Browning, M, Gabrielson, K. “Validation of the use of long-term indwelling jugular catheters in model of cardiotoxicity”, Contemporary Topics in Laboratory Animal Science, in press
Magno P, Giday SA, Gabrielson KL, Eun JS, Buscaglia J, Clarke JO, Ko C Jagannath SB, Canto MI, Kalloo AN, Kantsevoy, SV., “Endoscopic Ultrasound (EUS)-Guided Implantation of Radio-Opaque Marker into Mediastinal and Celiac Lymph Nodes is Safe and Effective”, Gastrointestinal Endoscopy, in press
Cooper TK, Gabrielson KL., “Spontaneous Lesions in the Reproductive Tract and Mammary Gland of Female Non-Human Primates”, Birth Defects Research Part B: Developmental and Reproductive Toxicology, in press
Lee SJ, Orita H, Gabrielson KL, Alvey S, Hagemann RL, Kuhajda FP, Gabrielson E, Pomper M., “FDG-PET for Pharmacodynamic Assessment of the Fatty Acid Synthase Inhibitor C75 in an Experimental Model of Lung Cancer”, Pharmacological Research, in press
Ruben D, Muratore N, Pin S, Gabrielson KL. “Effects of Bedding Substrates on Microsomal Enzymes in Rabbit Liver”, Journal of the American Association for Laboratory Animal Science, in press