Dr. Felix Gunawan
Cellular and molecular drivers of cardiac endothelial morphogenesis and plasticity
Vascular Biology / Angiogenesis
Development
Cell Biology / Molecular Biology
Heart Development
Hematopoietic Stem Cell Niche
A specialized population of endothelial cells, the endocardium, forms the first layer of the heart along with the contractile cardiac muscle. Although necessary for heart formation, development of the endocardium is poorly understood. Using zebrafish as a model system, we focus on elucidating the cellular and molecular processes driving endocardial morphogenesis and plasticity.
Our first focus is studying the formation of cardiac valves, which prevent backward blood flow in the heart. Complex tissue rearrangements – endocardial cell migration, proliferation and fibroblastic differentiation – form the functional valve. We are investigating the interplay between the valve cells and the extracellular environment that surround the valves. How the extracellular environment affects signalling pathway activation, biomechanical stiffness and cellular behaviours of valve cells is critical to address in our understanding of valve function.
Our second focus is elucidating the role of the heart as a hematopoietic niche. We discovered that the endocardium maintains hematopoietic stem and progenitor cells, which give rise to diverse blood lineages throughout life. We are investigating the molecular processes that promote endocardial differentiation into hematopoietic cells, focusing on candidate transcription factors from our single-cell RNA sequencing, and the role of cardiac contraction in generating endocardial hematopoietic cells.
Vita
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2004-2008 Honours Bachelor’s of Science, University of Toronto
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2008-2015 PhD (direct entry) in Cell and Systems Biology, University of Toronto
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2015-2021 Postdoc at Max Planck Institute for Heart and Lung Research, Bad Nauheim
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Since 2022 Cells-in-Motion Group Leader, Institute of Cell Biology, University of Münster
Selected references
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.
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.
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.
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.
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.