The candidate holds an MD with specialty in General Surgery and Vascular Surgery; she has a proven track record of research productivity and publications in leading journals in the fields of Vascular Surgery, Cardiovascular Medicine, and Tissue Engineering. The candidate's immediate objectives are to focus her efforts on the application and improvement of engineered cardiac tissues as a species-specific 3D platform to identify potential cardiotherapeutic agents, with the long-term goal of gaining independence as an investigator in biomedical research combining stem cell and tissue engineering technologies for the development of novel cardiovascular therapies. To accomplish this, the candidate and her mentoring team have crafted a 5-year synergistic career development plan and research strategy with the goal of establishing essential knowledge, skills and experience to transition to a tenure-track faculty position in biomedical research. The associated individualized research career training plan builds on the candidate's advanced experience with engineered cardiac tissues, stem cells, and surgical expertise, while addressing specific gaps in biomedical techniques and professional skills. The primary mentor is Dr. Kevin Costa, Director of Cardiovascular Cell and Tissue Engineering at the Icahn School of Medicine at Mount Sinai (ISMMS), whose integrated bioengineering approach to cardiac cell and tissue mechanobiology research is essential to the Specific Aims. The co-mentor, Dr. Roger Hajjar, is Director of the Cardiovascular Research Center (CVRC) and the Arthur and Janet C. Ross Professor of Medicine at ISMMS; he complements and enhances the training plan with world renowned expertise in cardiovascular translational research and mentorship which is ideally suited to guide the candidate's career development trajectory. The CVRC at Mount Sinai offers a rich environment for researcher development to facilitate productivity and cover all requirements of the Specific Aims. The career development plan focuses on a 3-tiered approach: 1) mentorship from a multidisciplinary group of experienced faculty and a candidate-specific tailored didactic program, 2) acquisition of professional survival skills and 3) a plan for structured transition to independence. The research objective of this award is to test the hypothesis that exosomes from mesenchymal stem cells as well as cardiac progenitor cells mediate the paracrine effects on enhancement of cardiac function after injury. Human engineered cardiac tissues will be used to test the effects of these exosomes for the first time on a species-specific model in a biologically controlled environment. Testing will also be conducted in vivo for assessment of the applicability of the in vitro findings. Lastly, exosomes will be processed for microRNA microarray to identify potential therapeutic candidates that may provide the benefits of stem cell therapy while circumventing the administration of live biologics, towards more effective and safer therapies for cardiac injury.
The significance of this proposal is driven by the potential impact of identifying novel therapies to enhance cardiac function after myocardial injury. We will explore exosomes from two clinically relevant adult stem cell therapy sources as potential cardio-therapeutic agents, evaluating their effect on cardiac contractility using engineered cardiac tissues as a 3D species-specific model. The identification of exosome components (microRNAs) associated with myocardial repair may lead to novel treatment strategies conferring the benefits of stem cell transplants while circumventing the potential risks of delivering live biologics.
|Ceholski, Delaine K; Turnbull, Irene C; Kong, Chi-Wing et al. (2018) Functional and transcriptomic insights into pathogenesis of R9C phospholamban mutation using human induced pluripotent stem cell-derived cardiomyocytes. J Mol Cell Cardiol 119:147-154|
|Kagan, Heather J; Belekdanian, Varujan D; Chen, Jiqiu et al. (2018) Coronary capillary blood flow in a rat model of congestive heart failure. J Appl Physiol (1985) 124:632-640|
|Ceholski, Delaine K; Turnbull, Irene C; Pothula, Venu et al. (2017) CXCR4 and CXCR7 play distinct roles in cardiac lineage specification and pharmacologic ?-adrenergic response. Stem Cell Res 23:77-86|