Yuka Morikawa, PhD

See Publications

Texas Heart Institute Positions

Assistant Research Investigator, Cardiomyocyte Renewal Laboratory

Publications

4862227 SS2CP8WX 1 alternatives-to-animal-experimentation 10 date desc Morikawa 2017 https://www.texasheart.org/wp-content/plugins/zotpress/

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Hill, M. C., Kadow, Z. A., Long, H. et al. (2022). Integrated multi-omic characterization of congenital heart disease. Nature. https://doi.org/10.1038/s41586-022-04989-3.

Aharonov, A., Shakked, A., Umansky, K. B. et al. (2020). ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration. Nat Cell Biol 22, 1346–1356. https://doi.org/10.1038/s41556-020-00588-4.

Monroe, T. O., Hill, M. C., Morikawa, Y. et al. (2019). YAP partially reprograms chromatin accessibility to directly induce adult cardiogenesis in vivo. Dev Cell 48, 765-779.e7. https://doi.org/10.1016/j.devcel.2019.01.017.

Li, L., Tao, G., Hill, M. C. et al. (2018). Pitx2 maintains mitochondrial function during regeneration to prevent myocardial fat deposition. Development 145. https://doi.org/10.1242/dev.168609.

Xiao, Y., Hill, M. C., Zhang, M. et al. (2018). Hippo signaling plays an essential role in cell state transitions during cardiac fibroblast development. Dev Cell 45, 153-169.e6. https://doi.org/10.1016/j.devcel.2018.03.019.

Leach, J. P., Heallen, T., Zhang, M. et al. (2017). Hippo pathway deficiency reverses systolic heart failure after infarction. Nature 550, 260–264. https://doi.org/10.1038/nature24045.

Morikawa, Y., Heallen, T., Leach, J. et al. (2017). Dystrophin-glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation. Nature 547, 227–231. https://doi.org/10.1038/nature22979.

Tao, G., Kahr, P. C., Morikawa, Y. et al. (2016). Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury. Nature 534, 119–123. https://doi.org/10.1038/nature17959.

Morikawa, Y., Zhang, M., Heallen, T. et al. (2015). Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice. Sci Signal 8, ra41. https://doi.org/10.1126/scisignal.2005781.

Wang, S., Lopez, A. L., Morikawa, Y. et al. (2015). Quantitative shear wave imaging optical coherence tomography for noncontact mechanical characterization of myocardium K. V. Larin and D. D. Sampson (eds.),. , 93270F. https://doi.org/10.1117/12.2078376.