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.
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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.
Recent Publications
For a full list of Field’s publications, find him on PubMed.
Reuter SP, Soonpaa MH, Field D, Simpson E, Rubart-von der Lohe M, Lee HK, Sridhar A, Ware SM, Green N, Li X, Ofner S, Marchuk DA, Wollert KC, Field LJ. (2023) Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation. Circulation. 147:142-153. [PMC9839600]
Tarasov KV, Chakir K, Riordon DR, Lyashkov AE, Ahmet I, Perino MG, Silvester AJ, Zhang J, Wang M, Lukyanenko YO, Qu JH, Barrera MC, Juhaszova M, Tarasova YS, Ziman B, Telljohann R, Kumar V, Ranek M, Lammons J, Bychkov R, de Cabo R, Jun S, Keceli G, Gupta A, Yang D, Aon MA, Adamo L, Morrell CH, Otu W, Carroll C, Chambers S, Paolocci N, Huynh T, Pacak K, Weiss R, Field L, Sollott SJ, Lakatta EG. (2022) A remarkable adaptive paradigm of heart performance and protection emerges in response to marked cardiac-specific overexpression of ADCY8. Elife. 11. [PMC9822292]
Reboll MR, Klede S, Taft MH, Cai CL, Field LJ, Lavine KJ, Koenig AL, Fleischauer J, Meyer J, Schambach A, Niessen HW, Kosanke M, van den Heuvel J, Pich A, Bauersachs J, Wu X, Zheng L, Wang Y, Korf-Klingebiel M, Polten F, Wollert KC. (2022) Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase. Science. 376:1343-1347. [PMC9838878]
Wollert KC, Field LJ. (2021) Cardioprotection vs. regeneration: the case of extracellular vesicle-derived microRNAs. Basic Res Cardiol. 116:20. [PMC7979608]
Anger M, Scheufele F, Ramanujam D, Meyer K, Nakajima H, Field LJ, Engelhardt S, Sarikas A. (2020) Genetic ablation of Cullin-RING E3 ubiquitin ligase 7 restrains pressure overload-induced myocardial fibrosis. PLoS One. 15:e0244096. [PMC7755222]
Tsai WC, Guo S, Olaopa MA, Field LJ, Yang J, Shen C, Chang CP, Chen PS, Rubart M. (2020) Complex Arrhythmia Syndrome in a Knock-In Mouse Model Carrier of the N98S Calm1 Mutation. Circulation. 142:1937-1955. [PMC7867118]
Firulli BA, George RM, Harkin J, Toolan KP, Gao H, Liu Y, Zhang W, Field LJ, Liu Y, Shou W, Payne RM, Rubart-von der Lohe M, Firulli AB. (2020) HAND1 loss-of-function within the embryonic myocardium reveals survivable congenital cardiac defects and adult heart failure. Cardiovasc Res. 116:605-618. [PMC7252443]
Eghbali A, Dukes A, Toischer K, Hasenfuss G, Field LJ. (2019) Cell Cycle-Mediated Cardiac Regeneration in the Mouse Heart. Curr Cardiol. 21:131. [PMC955293]
Zhu W, Reuter S, Field LJ. (2019) Targeted expression of cyclin D2 ameliorates late stage anthracycline cardiotoxicity. Cardiovasc Res. 115:960-965. [PMC6452322]
Soonpaa MH, Lafontant PJ, Reuter S, Scherschel JA, Srour EF, Zaruba MM, Rubart-von der Lohe M, Field LJ. (2018) Absence of Cardiomyocyte Differentiation Following Transplantation of Adult Cardiac-Resident Sca-1+ Cells Into Infarcted Mouse Hearts. Circulation. 138:2963-2966. [PMC6309891]
Wang J, Shen T, Zhu W, Dou L, Gu H, Zhang L, Yang Z, Chen H, Zhou Q, Sánchez ER, Field LJ, Mayo LD, Xie Z, Xiao D, Lin X, Shou W, Yong W. (2018) Protein phosphatase 5 and the tumor suppressor p53 down-regulate each other's activities in mice. J Biol Chem. 293:18218-18229.[PMC6254348]
Field LJ, Shou W, Markham L. (2018) 2017 Riley Heart Center Symposium on Cardiac Development: Development and Repair of the Ventricular Wall. Pediatr Cardiol. 39:1067-1068. [PMC6096844]
González-Rosa JM, Sharpe M, Field D, Soonpaa MH, Field LJ, Burns CE and Burns CG. (2018) Myocardial polyploidization creates a barrier to heart regeneration in zebrafish. Developmental Cell 44:433-446. [PMC5830170]
González-Rosa JM, Sharpe M, Field D, Soonpaa MH, Field LJ, Burns CE and Burns CG. (2018) Myocardial polyploidization creates a barrier to heart regeneration in zebrafish. Developmental Cell 44:433-446. [PMC5830170]
Soonpaa MH, Zebrowski D, Platt C, Rosenzweig A, Engel F and Field LJ. (2015) Cardiomyocyte cell cycle activity during preadolescence. Cell 163:781-782. PMID 26544927.
Zhu W, Zhang W, Shou W and Field LJ. (2014) p53 inhibition exacerbates late-stage anthracycline cardiotoxicity. Cardiovascular Research 103:81-89. PMCID4133592.
Reuter S, Soonpaa MH, Firulli AB, Chang AN and Field LJ. (2014) Recombinant Neuregulin 1 does not activate cardiomyocyte DNA synthesis in normal or infarcted adult mice. PlosOne 9:e115871. PMCID4278834.
Faculty Research Team
Additional Research Team Members
Additional research team members include Dorothy Field, MS (senior research technician), and Jon Cheung (visiting research associate in pediatrics).