NON-COMMUNICABLE DISEASES / Cardiovascular Disorders
Cardiovascular biology, aging, cardiac hypertrophy, adeno-associated virus (AAV), parabiosis, gene therapy
Description of Research
The Molecular Cardiology Laboratory’s main purpose is the study of the molecular mechanisms of cardiovascular biology of great interest for human cardiovascular diseases. In particular, our lab focuses on discovering and studying novel pathways that regulate cardiac hypertrophy, aging and metabolic diseases with specific attention to translating bench findings to new bedside approaches and strategies. Using a broad variety of techniques in genomics, stem cell biology, molecular biology, gene therapy, transgenic models and parabiosis, we approach cardiovascular problems relevant to human diseases to develop solutions that we validate by performing in vivo studies.
A great interest of the laboratory is the identification of novel circulating factors that regulate cardiac biology, including aging and hypertrophy. An important example is the demonstration that, using the parabiosis surgical technique, age-related cardiac hypertrophy can be reversed by exposure to a young circulatory environment. These experiments, performed in collaboration with the Lee Laboratory and the Wagers Laboratory at Harvard University, revealed that the cardiac hypertrophy of aging is at least in part mediated by circulating factors, and has led to the discovery that restoration of youthful levels of circulating Growth Differentiation Factor 11 (GDF11), a TGFβ family member, can reverse age-related cardiac hypertrophy and impact the aging phenotype of skeletal muscle and brain.
Our Group also works in close collaboration with other groups at ICGEB that have extensively studied viral vectors based on the adeno-associated virus (AAV) to deliver genes in the heart. This tool provides an enormous opportunity to translate to clinic new laboratory findings.
Sinha, M., Jang, Y.C., Oh, J., Khong, D., Wu, E.Y., Manohar, R., Miller, C., Regalado, S.G., Loffredo, F.S., Pancoast, J.R., Hirshman, M.F., Lebowitz, J., Shadrach, J.L., Cerletti, M., Kim, M.J., Serwold, T., Goodyear, L.J., Rosner, B., Lee, R.T., Wagers, A.J. 2014. Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle
Science 344, 649-652 PubMed link
Katsimpardi, L., Litterman, N.K., Schein, P.A., Miller, C.M., Loffredo, F.S., Wojtkiewicz, G.R., Chen, J.W., Lee, R.T., Wagers, A.J., Rubin, L.L. 2014. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 344, 630-634 PubMed link
Loffredo, F.S., Pancoast, J.R., Cai, L., Vannelli, T., Dong, J., Lee, R.T., Patwari, P. 2014. Targeted Delivery to Cartilage Is Critical for In Vivo Efficacy of Insulin-like Growth Factor-1. Arthritis Rheumatol PubMed link
Loffredo, F.S., Steinhauser, M.L., Jay, S.M., Gannon, J., Pancoast, J.R., Yalamanchi, P., Sinha, M., Dall’Osso, C., Khong, D., Shadrach, J.L., Miller, C.M., Singer, B.S., Stewart, A., Psychogios, N., Gerszten, R.E., Hartigan, A.J., Kim, M.J., Serwold, T., Wagers, A.J., Lee, R.T. 2013. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell 153, 828-839 PubMed link
Loffredo, F.S., Steinhauser, M.L., Gannon, J., Lee, R.T. 2011. Bone-marrow derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell 8, 389-398 PubMed link