We study factors and mechanisms that control heart development to understand the pathogenesis of congenital heart disease as well as to gain insights into potential repairing mechanisms to combat heart disease. We use mice, mouse and human stem cells as model systems in our research. We apply an integrated approach of genetics, developmental, molecular and systems biology and advanced single cell technologies and CRISPR gene editing to address three major questions: (1) How individual cardiac cells and lineages are specified, maintained, or diversified during cardiac development, disease, aging, or regeneration?  (2) How cell-cell, or cell-environment communications are modulated to control cardiac functions under these conditions? (3) How fetal cardiac gene program is controlled during development and reactivated in the diseased heart? 

Selected Pulications

1. Lu P, Wang Y, Wu B, Liu Y, Wang Y, Liu Y, Cheng W, Feng X, Yuan X, Atteya MM, Ferro H, Sugi Y, Rydquist G, Esmaily M, Butcher JT, Chang CP, Lenz J, Zheng D, Zhou B. (2022) A SOX17-PDGFB signaling axis regulates aortic root development. Nat Commun Jul 13;13(1):4065.  doi: 10.1038/s41467-022-31815-1

2. Lu P, Wu B, Feng X, Cheng W, Kitsis RN, Zhou B. (2022) Cardiac Myosin Heavy Chain Reporter Mice to Study Heart Development and Disease. Circ Res https://doi.org/10.1161/CIRCRESAHA. 122.321461

3. Lu P, Wang Y, Liu Y,  Wang Y,  Wu B, Zheng D, Harvey RP, Zhou B. Perinatal angiogenesis from preexisting coronary vessels via DLL4/NOTCH1 signaling. Nat Cell Biol 2021 Sep;23(9):967-977.

4. Wang Y, Lu P, Jiang L, Wu B, Zhou B. Control of sinus venous valve and sinoatrial node development by endocardial NOTCH1. Cardiovasc Res. 2020 Jul 1;116(8):1473-1486.

5. Gee T, Farrar E, Wang Y, Wu B, Hsu K, Zhou B, Butcher J. NFκB (Nuclear Factor κ-Light-Chain Enhancer of Activated B Cells) Activity Regulates Cell-Type-Specific and Context-Specific Susceptibility to Calcification in the Aortic Valve. Arterioscler Thromb Vasc Biol. 2020 Mar;40(3):638-655. 

6. Chen D, Zhu X, Kofler N, Wang Y, Zhou B, Simons M. FRS2α-dependent cell fate transition during endocardial cushion morphogenesis. Dev Biol.2020 Feb 1;458(1):88-97. 

7. Liu Y, Lu P, Wang Y, Morrow BE, Zhou B, Zheng D. Spatiotemporal Gene Coexpression and Regulation in Mouse Cardiomyocytes of Early Cardiac Morphogenesis. J Am Heart Assoc. 2019 Aug 6;8(15):e012941. 

8. Shigeta A, Huang V, Zuo J, Besada R, Nakashima Y, Lu Y, Ding Y, Pellegrini M, Kulkarni RP, Hsiai T, Deb A, Zhou B, Nakano H, Nakano A.Endocardially Derived Macrophages Are Essential for Valvular Remodeling. Dev Cell. 2019 Mar 11;48(5):617-630.e3

9. Wang Y, Lu P, Wu B, Morrow BE, Zhou B. NOTCH maintains developmental cardiac gene network through WNT5A. J Mol Cell Cardiol. 2018 Dec;125:98-105. 

10. Wang Y, Lu P, Wu B, Riascos-Bernal DF, Sibinga NES, Valenta T, Basler K, Zhou B. Myocardial β-Catenin-BMP2 signaling promotes mesenchymal cell proliferation during endocardial cushion formation. J Mol Cell Cardiol. 2018 Oct;123:150-158. 

11. Boogerd CJ, Zhu X, Aneas I, Sakabe N, Zhang L, Sobreira DR, Montefiori L, Bogomolovas J, Joslin AC, Zhou B, Chen J, Nobrega MA, Evans SM.Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development. Circ Res. 2018 Aug 3;123(4):428-442. 

12. del Monte-Nieto G, Ramialison M,. Cherian AV, Wu B, Aharonov A, D’Uva G, Bourke LM, Pitulescu ME, Chen H, Shou W, Adams RH, Harten SK, Tzahor E, Zhou B, Harvey RP. (2018) Extracellular matrix dynamics reveals the building plan for cardiac trabeculation. Nature 557(7705):439-445

13. Zhang D, Wang Y, Lu P, Wang P, Xinchun Yuan X, Yan J, Cai C, Chang CP, Zheng D, Wu B, Zhou B. (2017) REST regulates the cell cycle for cardiac development and regeneration. Nat Commun; 8(1):1979.

14. Wang Y, Wu B, Lu P, Zhang D, Wu B, Varshney S, Del Monte-Nieto G, Zhuang Z, Charafeddine R, Kramer AH, Sibinga NE, Frangogiannis NG, Kitsis RN, Adams RH, Alittalo K, Sharp DJ, Harvey RP, Stanley P, Zhou B. (2017) Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1. Nat Commun 18;8(1):578  

15. Wu B, Wang Y, Xiao F, Butcher JT, Yutezy KE, Zhou B. (2017) Developmental mechanisms in aortic valve malformation and disease. Annu Rev Physiol 79:21-41 

16. Zhang D, Wu B, Wang P, Wang Y, Nechiporuk T, Floss T, Greally JM, Zheng D, Zhou B. (2017) Non-CpG methylation by DNMT3B facilitates REST binding and gene silencing in developing mouse hearts. Nucleic Acids Res 45:3102-3115

17. Wang, Y, Wu B, Farrar E, Alfieri CM, Lui, W, Lu P, Zhang D, Mao K, Chu M, Yang D, Xu D, Rauchman M, Taylor V, Yutzey KE, Butcher JT, Zhou B. (2017) Notch-Tnf signaling is required for development and homeostasis of arterial valves. Eur Heart J 38:675-686

18. Goddard L, Chen M, Ramalingam H, Bamezai S, Yang, J, Morley M, Wang T, Jameson S, Morrisey E, Zhou B, Thomas C, Kahn M. (2017) Hemodynamic forces sculpt developing heart valves through a KLF2-Wnt9b paracrine signaling axis. Dev Cell 43(3):274-289

19. Han P, Li W, Lin CH, Yang J, Shang Q, Nuernberg S, Jin K, Xu W, Lin CY, Lin CJ, Xiong Y, Chien H, Zhou B, Ashley E, Bernstein D, Chen PS, Chen HS, Quertermous T, Chang CP. (2014) A long non-coding RNA protects the heart from pathological hypertrophy. Nature, 514:102-106 

20. Wu B, Zhang Z, Lui W, Chen X, Moreno-Rodriquez RA, Wang Y, Chamberlain A, Markwald RA, O’Rourke B, Sharp DJ, Lenz J, Baldwin HS, Chang CP, Zhou B. (2012) Endocardial Cells Form the Coronary Arteries by Angiogenesis through Myocardial to Endocardial VEGF Signaling. Cell 151:1083-1096. 

21. Lin CY, Lin CJ, Chen CH, Zhou B*, Chang CP*. (2012) Partitioning the heart: mechanisms of cardiac septation and valve development. Development 139:3277-99. *Corresponding authors.

22. Wu B, Wang Y, Lui W, Langworthy M, Tompkins KL, Hatzopoulos AK, Baldwin, HS, Zhou B. (2011) Nfatc1 Coordinates valve endocardial cell lineage development required for heart valve formation. Circ Res 109:183-192.

22. Hang CT, Yang J, Han P, Cheng HL, Shang C, Ashley E, Zhou B, Chang CP. (2010) Chromatin regulation by Brg1 underlies heart muscle development and disease. Nature 466:62-7