Core D is subdivided in two parts: Imaging (part 1), under the responsibility of Dr. Nahrendorf, and Confocal and Two-Photon Microscopy (part 2) under the responsibility of Dr. Kajstura. Part 1 will provide sophisticated non-invasive, diagnostic imaging by MRI and other instrumentations to characterize the cardiac phenotype of aging mice and the effects of cardiac stem cells (CSCs) on the reversal of the aging process. These determinations are required for Projects 1, 2, and 4. By this approach, the anatomical and functional characteristics of myocardial aging will be followed over time in the same animals to validate targets and linked biomarkers, and assess the efficacy of emerging therapeutics. Part 2 will support all 4 Projects since they require complex immunolabeling methodologies and the necessity to distinguish actual signals from tissue autofluorescence by confocal microscopy. Additionally, the evaluation whether sarcomere stretching alone or mechanical deformation of resident CSCs promotes Ca2+ oscillatory events and cell cycle reentry will need two-photon microscopy. This strategy is particularly relevant to Projects 3 and 4. Collectively, part 1 and part 2 of Core D will ensure an unmatched level of technology and expertise, essential to achieve the goals of this PPG application. Importantly, Dr. Nahrendorf and Dr. Kajstura have been working closely together in the acquisition of the Preliminary Data included in the proposal.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-7)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Borghetti, Giulia; Eisenberg, Carol A; Signore, Sergio et al. (2018) Notch signaling modulates the electrical behavior of cardiomyocytes. Am J Physiol Heart Circ Physiol 314:H68-H81
Wysoczynski, Marcin; Guo, Yiru; Moore 4th, Joseph B et al. (2017) Myocardial Reparative Properties of Cardiac Mesenchymal Cells Isolated on the Basis of Adherence. J Am Coll Cardiol 69:1824-1838
Meo, Marianna; Meste, Olivier; Signore, Sergio et al. (2016) Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm. J Am Heart Assoc 5:
Sorrentino, Andrea; Signore, Sergio; Qanud, Khaled et al. (2016) Myocyte repolarization modulates myocardial function in aging dogs. Am J Physiol Heart Circ Physiol 310:H873-90
Signore, Sergio; Sorrentino, Andrea; Borghetti, Giulia et al. (2015) Late Na(+) current and protracted electrical recovery are critical determinants of the aging myopathy. Nat Commun 6:8803
Moccetti, Tiziano; Leri, Annarosa; Goichberg, Polina et al. (2015) A Novel Class of Human Cardiac Stem Cells. Cardiol Rev 23:189-200
Leri, Annarosa; Rota, Marcello; Pasqualini, Francesco S et al. (2015) Origin of cardiomyocytes in the adult heart. Circ Res 116:150-66
D'Amario, Domenico; Leone, Antonio M; Iaconelli, Antonio et al. (2014) Growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery. Circulation 129:157-72
Leri, Annarosa; Rota, Marcello; Hosoda, Toru et al. (2014) Cardiac stem cell niches. Stem Cell Res 13:631-46
Sanada, Fumihiro; Kim, Junghyun; Czarna, Anna et al. (2014) c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy. Circ Res 114:41-55

Showing the most recent 10 out of 25 publications