© Raphael Schleutker

Research Topic

Our research studies the dynamic cellular interfaces that drive heart formation. We focus on the development of endocardial cells, specialized vascular cells that line the heart. These cells form important specialized structures such as the heart valves, which prevent retrograde blood flow, and exhibit plasticity to differentiate into other cardiovascular cells.

We are elucidating the molecular and the biophysical factors that drive active endocardial cell morphogenesis, including migration, proliferation, and differentiation, to form the mature valves. Our focus within the CRC is to functionally investigate different extracellular matrix networks and inter-tissue communications in regulating valve tissue size, cell population dynamics, and biomechanical rigidity. We are also investigating the potency of endocardial cells to differentiate into other cells, notably valve fibroblast cells and hematopoietic stem cells, and the molecular and biomechanical pathways that regulate this process. These projects synchronize into our long-term goal to understand the processes required for optimal heart development and function. 

Selected Publications

  • Gentile A., Bensimon-Brito A., Priya R., Maischein HMM., Piesker J., Günther S., Gunawan F. *, ¶, Stainier DYR.*,¶ (2021) The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression. eLife: Jun 21;10:e66143. doi.org/10.7554/eLife.66143.
  • Gunawan F. *, ¶, Priya R.*, ¶, Stainier DYR¶. (2021) Sculpting the heart: cellular mechanisms shaping valves and trabeculae. Current Opinion in Cell Biology Jun 17;73:26-34. doi.org/10.1016/j.ceb.2021.04.009.
  • Gunawan F.*, ¶, Gentile A.*, Gauvrit S., Stainier DYR.¶, Bensimon-Brito A.¶ (2020) Nfatc1 mediates interstitial cell formation during heart valve development. Circulation Research Apr 10:126(8):968-984. doi: 10.1161/CIRCRESAHA.119.315992.
  • Fukuda R., Gunawan F., Ramadass R., Beisaw A., Konzer A., Mullapudi S.T., Gentile A., Graumann J., Maischein H.M., and Stainier D. (2019) Mechanical forces regulate cardiomyocyte myofilament maturation via the VCL-SSH1-CFL axis. Developmental Cell Oct 21; 51, 1–16. doi: 10.1016/j.devcel.2019.08.006. 
  • Gunawan F.¶, Gentile A., Fukuda R., Tsedeke AT., Jimenez-Amilburu V., Ramadass R., Iida A., Sehara-Fujisawa A., Stainier D.¶ (2019) Focal adhesions are essential to drive zebrafish heart valve morphogenesis. Journal of Cell Biology Mar 4; 218(3):1039-1054. doi: 10.1083/jcb.201807175 (Faculty1000 Recommendation by Guido Serini).

* Equal contributions
¶ Last, corresponding authors