“Cardiomyocyte Cell Cycle Activity in Injured Hearts”.
Dr. Field serves as PI of this R01 application, which proposes to establish the intrinsic variability in ventricular cardiomyocyte cell cycle reentry following permeant coronary artery ligation. It also proposes to determine if observed clusters of cell cycle activity arise from clonal expansion of a limited number of cells. Other studies will test the hypothesis that the nature of myocardial injury can profoundly influence the degree of cardiomyocyte cell cycle reentry in the remote ventricular myocardium and will determine the degree to which genetic background impacts these events. Collectively, the proposed experiments will provide a comprehensive atlas of the cardiomyocyte cell cycle response to commonly used and clinically relevant myocardial injury models. Ultimately, these might provide useful insight for the development of interventional strategies to enhance the intrinsic regenerative capacity of the myocardium following injury.
“Morphogenesis and Growth of the Ventricular Wall in Development and Disease”.
Dr. Field serves as a collaborating investigator of this PPG application, which is led by Anthony Firulli, PhD. This application proposes to elucidate mechanisms that regulate growth and morphogenesis of the ventricle during development. Project 1 studies the molecular mechanisms contributing to the genesis of CHDs in an animal model of x-linked heterotaxy. Project 2 studies the molecular mechanisms regulating ventricular septation and papillary muscle formation. Project 3 studies the molecular mechanisms regulating compaction of the left ventricle during cardiac development. Ultimately, the studies proposed in this Program Project Grant application will illustrate how events that occur prior to overt heart formation, during early cardiac development and during late maturation of the ventricular wall are sequentially integrated for normal cardiac morphogenesis. Defining the molecular regulation of these events will provide important insight into potential interventions aiming to mitigate the deleterious impact of CHD.
González-Rosa, J.M., Sharpe, M., Field, D., Soonpaa, M.H., Field, L.J., Burns, C.E. and Burns, C.G. (2018) Myocardial polyploidization creates a barrier to heart regeneration in zebrafish. Developmental Cell 44:433-446. [PMC5830170]
Toischer, K., Zhu, W., Hünlich, M., Mohamed, B.A., Khadjeh, S., Reuter, S.P., Schäfer, K., Ramanujam, D., Engelhardt, S., Field, L.J.* and Hasenfuss, G.* (2017) Cardiomyocyte proliferation prevents failure in pressure but not volume overload. The Journal of Clinical Investigation 127:4285-4296, PMID:29083322, PMCID in progress]. *: corresponding authors, equal contribution.
Soonpaa, M.H. Zebrowski, D., Platt, C., Rosenzweig, A., Engel, F. and Field, L.J. (2015) Cardiomyocyte cell cycle activity during preadolescence. Cell 163:781-782. PMID 26544927.
Zhu, W., Zhang, W., Shou, W. and Field, L.J. (2014) p53 inhibition exacerbates late-stage anthracycline cardiotoxicity. Cardiovascular Research 103:81-89. PMCID4133592.
Reuter, S., Soonpaa, M.H., Firulli, A.B., Chang, A.N. and Field, L.J. (2014) Recombinant Neuregulin 1 does not activate cardiomyocyte DNA synthesis in normal or infarcted adult mice. PlosOne 9:e115871. PMCID4278834.
Additional Research Team Members
Additional research team members include Dorothy Field, MS (senior research technician), and Jon Cheung (visiting research associate in pediatrics).