Field Lab

The research laboratory of Loren Field, PhD, focuses on regenerative growth of the heart. Although the adult mammalian heart retains some capacity for cardiomyocyte renewal (resulting from cardiomyocyte proliferation and/or cardiomyogenic stem cell activity), the magnitude of this regenerative process is insufficient to effect repair following substantive myocardial damage.  The Field Lab has a long-standing interest in developing strategies to monitor the intrinsic rates of cardiomyocyte cell cycle renewal in normal and injured adult hearts, as well as developing strategies to induce regenerative growth following myocardial injury.

Active Research

The Field Lab focuses on two approaches to promote regenerative growth of the heart.  The first approach relies on the transplantation of cardiomyocytes or cardiomyogenic stem cells into the damaged myocardium.  For example, the lab has shown that cardiomyocytes derived from both fetal and embryonic stem cells are able to structurally integrate into the adult myocardium and participate in a functional syncytium with the host heart.

The second approach to promote regenerative growth entails inducing proliferation in surviving cardiomyocytes following myocardial injury. The lab has identified a number of gene products which, when expressed in cardiomyocytes, induce proliferation. For example, targeted expression of the G1/S regulatory protein cyclin D2 results in a 50 percent reduction in infarct size and a concomitant 90 percent recovery in cardiac function within 180 days following permanent coronary artery occlusion. Current efforts in studying cardiomyocyte cell cycle regulation are focused on using a recently developed medium-throughput assay to quantitatively reconstruct cumulative cardiomyocyte cell cycle activity in 3D models.  The lab is pursuing three projects: generation of 3D atlases to track intrinsic cardiac renewal in uninjured adult hearts; generation of 3D atlases to track intrinsic cardiac renewal in infarcted adult hearts; and identification of genetic variants which impact the intrinsic cardiac renewal rate.

Research Funding

“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.

Recent Publications

For a full list of Dr. Field’s publications, find him on PubMed.

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.

Faculty Research Team

Loren J. Field, PhD

Loren J. Field, PhD

Professor of Medicine
Mark H. Soonpaa, PhD

Mark H. Soonpaa, PhD

Assistant Scientist in Medicine
Sean P. Reuter

Sean P. Reuter

Research Associate in Pediatrics

Additional Research Team Members

Additional research team members include Dorothy Field, MS (senior research technician), and Jon Cheung (visiting research associate in pediatrics).