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30 results on '"Davaapil, Hongorzul"'

4. PRELP secreted from mural cells protects the function of blood brain barrier through regulation of endothelial cell-cell integrity

Author

Davaapil, Hongorzul, primary, Hopkins, Jack, additional, Bonnin, Nadia, additional, Papadaki, Vasiliki, additional, Leung, Alex, additional, Kosuge, Hirofumi, additional, Tashima, Takumi, additional, Nakakido, Makoto, additional, Sekido, Ryohei, additional, Tsumoto, Kouhei, additional, Sagoo, Mandeep S., additional, and Ohnuma, Shin-Ichi, additional

Published
2023
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5. Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration

Author

Bargehr, Johannes, Ong, Lay Ping, Colzani, Maria, Davaapil, Hongorzul, Hofsteen, Peter, Bhandari, Shiv, Gambardella, Laure, Le Novère, Nicolas, Iyer, Dharini, Sampaziotis, Fotios, Weinberger, Florian, Bertero, Alessandro, Leonard, Andrea, Bernard, William G., Martinson, Amy, Figg, Nichola, Regnier, Michael, Bennett, Martin R., Murry, Charles E., and Sinha, Sanjay

Published
2019
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6. Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients

Author

Yin, Xiaoke, Wanga, Shaynah, Fellows, Adam, Barallobre-Barreiro, Javier, Lu, Ruifang, Davaapil, Hongorzul, Franken, Romy, Fava, Marika, Baig, Ferheen, Skroblin, Philipp, Xing, Qiuru, Koolbergen, David R, Groenink, Maarten, Zwinderman, Aeilko H, Balm, Ron, de Vries, Carlie J.M, Mulder, Barbara J.M, Viner, Rosa, Jahangiri, Marjan, Reinhardt, Dieter P, Sinha, Sanjay, de Waard, Vivian, and Mayr, Manuel

Published
2019
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8. The small leucine-rich repeat secreted protein Asporin induces eyes in Xenopus embryos through the IGF signalling pathway

Author

Luehders, Kristin, Sasai, Noriaki, Davaapil, Hongorzul, Kurosawa-Yoshida, Maiko, Hiura, Hitoshi, Brah, Tara, Ohnuma, Shin-ichi, Luehders, Kristin, Sasai, Noriaki, Davaapil, Hongorzul, Kurosawa-Yoshida, Maiko, Hiura, Hitoshi, Brah, Tara, and Ohnuma, Shin-ichi

Abstract

Small leucine-rich repeat proteoglycan (SLRP) family proteins play important roles in a number of biological events. Here, we demonstrate that the SLRP family member Asporin (ASPN) plays a crucial role in the early stages of eye development in Xenopus embryos. During embryogenesis, ASPN is broadly expressed in the neuroectoderm of the embryo. Overexpression of ASPN causes the induction of ectopic eyes. By contrast, blocking ASPN function with a morpholino oligonucleotide (ASPN-MO) inhibits eye formation, indicating that ASPN is an essential factor for eye development. Detailed molecular analyses revealed that ASPN interacts with insulin growth factor receptor (IGFR) and is essential for activating the IGF receptor-mediated intracellular signalling pathway. Moreover, ASPN perturbed the Wnt, BMP and Activin signalling pathways, suggesting that ASPN thereby creates a favourable environment in which the IGF signal can dominate. ASPN is thus a novel secreted molecule essential for eye induction through the coordination of multiple signalling pathways.

Published
2023

10. PRELP Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma Progression

Author

Hopkins, Jack, primary, Asada, Ken, additional, Leung, Alex, additional, Papadaki, Vasiliki, additional, Davaapil, Hongorzul, additional, Morrison, Matthew, additional, Orita, Tomoko, additional, Sekido, Ryohei, additional, Kosuge, Hirofumi, additional, Reddy, M. Ashwin, additional, Kimura, Kazuhiro, additional, Mitani, Akihisa, additional, Tsumoto, Kouhei, additional, Hamamoto, Ryuji, additional, Sagoo, Mandeep S., additional, and Ohnuma, Shin-ichi, additional

Published
2022
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16. SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function

Author

Marchiano, Silvia, primary, Hsiang, Tien-Ying, additional, Khanna, Akshita, additional, Higashi, Ty, additional, Whitmore, Leanne S., additional, Bargehr, Johannes, additional, Davaapil, Hongorzul, additional, Chang, Jean, additional, Smith, Elise, additional, Ong, Lay Ping, additional, Colzani, Maria, additional, Reinecke, Hans, additional, Yang, Xiulan, additional, Pabon, Lil, additional, Sinha, Sanjay, additional, Najafian, Behzad, additional, Sniadecki, Nathan J., additional, Bertero, Alessandro, additional, Gale, Michael, additional, and Murry, Charles E., additional

Published
2021
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17. Densified Collagen Tubular Grafts for Human Tissue Replacement and Disease Modelling Applications

Author

Justin, Alexander W, primary, Cammarata, Federico, additional, Guy, Andrew A, additional, Estevez, Silas R, additional, Burgess, Sebastian, additional, Davaapil, Hongorzul, additional, Stavropoulou-Tatla, Agavi, additional, Ong, John, additional, Jacob, Aishwarya G, additional, Saeb-Parsy, Kourosh, additional, Sinha, Sanjay, additional, and Markaki, Athina E, additional

Published
2021
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18. Two Secreted Proteoglycans, Activators of Urothelial Cell–Cell Adhesion, Negatively Contribute to Bladder Cancer Initiation and Progression

Author

Papadaki, Vasiliki, primary, Asada, Ken, additional, Watson, Julie K., additional, Tamura, Toshiya, additional, Leung, Alex, additional, Hopkins, Jack, additional, Dellett, Margaret, additional, Sasai, Noriaki, additional, Davaapil, Hongorzul, additional, Nik-Zainal, Serena, additional, Longbottom, Rebecca, additional, Nakakido, Makoto, additional, Torii, Ryo, additional, Veerakumarasivam, Abhi, additional, Kaneko, Syuzo, additional, Sagoo, Mandeep S., additional, Murphy, Gillian, additional, Mitani, Akihisa, additional, Tsumoto, Kohei, additional, Kelly, John D., additional, Hamamoto, Ryuji, additional, and Ohnuma, Shin-ichi, additional

Published
2020
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21. The small leucine-rich repeat secreted protein Asporin induces eyes in Xenopus embryos through the IGF signalling pathway

Author

Luehders, Kristin, 80391960, Sasai, Noriaki, Davaapil, Hongorzul, Kurosawa-Yoshida, Maiko, Hiura, Hitoshi, Brah, Tara, Ohnuma, Shin-ichi, Luehders, Kristin, 80391960, Sasai, Noriaki, Davaapil, Hongorzul, Kurosawa-Yoshida, Maiko, Hiura, Hitoshi, Brah, Tara, and Ohnuma, Shin-ichi

Abstract

application/pdf, Small leucine-rich repeat proteoglycan (SLRP) family proteins play important roles in a number of biological events. Here, we demonstrate that the SLRP family member Asporin (ASPN) plays a crucial role in the early stages of eye development in Xenopus embryos. During embryogenesis, ASPN is broadly expressed in the neuroectoderm of the embryo. Overexpression of ASPN causes the induction of ectopic eyes. By contrast, blocking ASPN function with a morpholino oligonucleotide (ASPN-MO) inhibits eye formation, indicating that ASPN is an essential factor for eye development. Detailed molecular analyses revealed that ASPN interacts with insulin growth factor receptor (IGFR) and is essential for activating the IGF receptor-mediated intracellular signalling pathway. Moreover, ASPN perturbed the Wnt, BMP and Activin signalling pathways, suggesting that ASPN thereby creates a favourable environment in which the IGF signal can dominate. ASPN is thus a novel secreted molecule essential for eye induction through the coordination of multiple signalling pathways.

Published
2015

25. Conserved and novel functions of programmed cellular senescence during vertebrate development.

Author

Davaapil, Hongorzul, Brockes, Jeremy P., and Yun, Maximina H.

Subjects
*AGING, *DEVELOPMENTAL biology, *CELL cycle
Abstract

Cellular senescence, a form of stable cell cycle arrest that is traditionally associated with tumour suppression, has been recently found to occur during mammalian development. Here, we show that cell senescence is an intrinsic part of the developmental programme in amphibians. Programmed senescence occurs in specific structures during defined time windows during amphibian development. It contributes to the physiological degeneration of the amphibian pronephros and to the development of the cement gland and oral cavity. In both contexts, senescence depends on TGFβ but is independent of ERK/MAPK activation. Furthermore, elimination of senescent cells through temporary TGFβ inhibition leads to developmental defects. Our findings uncover conserved and new roles of senescence in vertebrate organogenesis and support the view that cellular senescence may have arisen in evolution as a developmental mechanism. [ABSTRACT FROM AUTHOR]

Published
2017
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27. Densified collagen tubular grafts for human tissue replacement and disease modelling applications

Author

Justin, Alexander W., Cammarata, Federico, Guy, Andrew A., Estevez, Silas R., Burgess, Sebastian, Davaapil, Hongorzul, Stavropoulou-Tatla, Agavi, Ong, John, Jacob, Aishwarya G., Saeb-Parsy, Kourosh, Sinha, Sanjay, and Markaki, Athina E.

Abstract

There is a significant need across multiple indications for an off-the-shelfbioengineered tubular graft which fulfils the mechanical and biological requirements for implantation and function but does not necessarily require cells for manufacture or deployment. Herein, we present a tissue-like tubular construct using a cell-free, materials-based method of manufacture, utilizing densified collagen hydrogel. Our tubular grafts are seamless, mechanically strong, customizable in terms of lumen diameter and wall thickness, and display a uniform fibril density across the wall thickness and along the tube length. While the method enables acellular grafts to be generated rapidly, inexpensively, and to a wide range of specifications, the cell-compatible densification process also enables a high density of cells to be incorporated uniformly into the walls of the tubes, which we show can be maintained under perfusion culture. Additionally, the method enables tubes consisting of distinct cell domains with cellular configurations at the boundaries which may be useful for modelling aortic disease. Further, we demonstrate additional steps which allow for luminal surface patterning. These results highlight the universality of this approach and its potential for developing the next generation of bioengineered grafts.

Published
2022
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28. Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration

Author

Bargehr, Johannes, Ong, Lay Ping, Colzani, Maria, Davaapil, Hongorzul, Hofsteen, Peter, Bhandari, Shiv, Gambardella, Laure, Le Novère, Nicolas, Iyer, Dharini, Sampaziotis, Fotios, Weinberger, Florian, Bertero, Alessandro, Leonard, Andrea, Bernard, William G, Martinson, Amy, Figg, Nichola, Regnier, Michael, Bennett, Martin R, Murry, Charles E, and Sinha, Sanjay

Subjects
Male, Tissue Engineering, Human Embryonic Stem Cells, Myocardial Infarction, Heart, Chick Embryo, 3. Good health, Rats, Rats, Sprague-Dawley, Rats, Nude, Gene Expression Regulation, Animals, Humans, Regeneration, Myocytes, Cardiac
Abstract

The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells. Transplanted epicardial cells formed persistent fibroblast grafts in infarcted hearts. Cotransplantation of hESC-derived epicardial cells and cardiomyocytes doubled graft cardiomyocyte proliferation rates in vivo, resulting in 2.6-fold greater cardiac graft size and simultaneously augmenting graft and host vascularization. Notably, cotransplantation improved systolic function compared with hearts receiving either cardiomyocytes alone, epicardial cells alone or vehicle. The ability of epicardial cells to enhance cardiac graft size and function makes them a promising adjuvant therapeutic for cardiac repair.

29. A phenotypic screen of Marfan syndrome iPSC-derived vascular smooth muscle cells uncovers GSK3β as a new target

Author

Hongorzul Davaapil, Madeline McNamara, Alessandra Granata, Robyn G.C. Macrae, Mei Hirano, Martina Fitzek, Jose Antonio Aragon-Martin, Anne Child, David M. Smith, Sanjay Sinha, Davaapil, Hongorzul [0000-0001-5947-9317], Sinha, Sanjay [0000-0001-5900-1209], and Apollo - University of Cambridge Repository

Subjects
musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, iPSC, Glycogen Synthase Kinase 3 beta, VSMC, Induced Pluripotent Stem Cells, GSK3β, thoracic aneurysm, Cell Biology, Biochemistry, drug screen, Muscle, Smooth, Vascular, Marfan Syndrome, MFS, disease modeling, Genetics, cardiovascular system, Animals, Humans, cardiovascular diseases, vascular smooth muscle cell, skin and connective tissue diseases, Aorta, Developmental Biology
Abstract

Marfan syndrome (MFS) is a rare connective tissue disorder caused by mutations in FBN1. Patients with MFS notably suffer from aortic aneurysm and dissection. Despite considerable effort, animal models have proven to be poorly predictive for therapeutic intervention in human aortic disease. Using a “humanised” model system may be more appropriate in identifying new therapeutic targets. Patient-derived induced pluripotent stem cells can be differentiated into vascular smooth muscle cells (VSMCs) and recapitulate major features of MFS. We have screened 1,022 small molecules in our in vitro model, exploiting the highly-proteolytic nature of MFS-VSMCs, and identified 36 effective compounds. Further analysis identified GSK3β as a recurring target in the compound screen. GSK3β inhibition/knockdown did not ameliorate the proliferation defect in MFS-VSMCs but improved MFS-VSMC apoptosis and proteolysis. To conclude, we have identified GSK3β as a novel target for MFS, forming the foundation for future work in MFS and other aortic diseases.

Published
2022
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