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Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression (2022)
Journal Article
Ahmed, S., Kurusamy, S., David, E. L. S., Khan, K., Kalyanakrishnan, K., Ian-Gobo, M., …Armesilla, A. L. (2022). Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression. Scientific Reports, 12(1), Article 14730. https://doi.org/10.1038/s41598-022-19172-x

Angiogenesis is a multi-factorial physiological process deregulated in human diseases characterised by excessive or insufficient blood vessel formation. Emerging evidence highlights a novel role for microRNAs as regulators of angiogenesis. Previous s... Read More about Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression.

A Workflow to Track and Analyze Endothelial Migration During Vascular Development in Zebrafish Embryos Using Lightsheet Microscopy (2022)
Book Chapter
Wilkinson, R. N. (2022). A Workflow to Track and Analyze Endothelial Migration During Vascular Development in Zebrafish Embryos Using Lightsheet Microscopy. . Springer US. https://doi.org/10.1007/978-1-0716-2059-5_2

Zebrafish allow unrivalled in vivo imaging of vascular development due to their optical translucency and the availability of transgenic lines which fluorescently label cells and tissues of interest. Advances in light sheet fluorescence microscopy all... Read More about A Workflow to Track and Analyze Endothelial Migration During Vascular Development in Zebrafish Embryos Using Lightsheet Microscopy.

Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids (2021)
Journal Article
Cirillo, S., Tomeh, M. A., Wilkinson, R. N., Hill, C., Brown, S., & Zhao, X. (2021). Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids. ACS Applied Materials and Interfaces, 13(42), 49713-49728. https://doi.org/10.1021/acsami.1c14761

Antimicrobial/anticancer peptides (AMPs/ACPs) have shown promising results as new therapeutic agents in cancer thearpy. Among them, the designed amphiphilic α-helical peptide G(IIKK)3I-NH2 (G3) displayed great affinity and specificity in targeting ca... Read More about Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids.

Zebrafish as a tractable model of human cardiovascular disease (2021)
Journal Article
Bowley, G., Kugler, E., Wilkinson, R., Lawrie, A., Eeden, F., Chico, T. J. A., …Serbanovic‐Canic, J. (2022). Zebrafish as a tractable model of human cardiovascular disease. British Journal of Pharmacology, 179(5), 900-917. https://doi.org/10.1111/bph.15473

Mammalian models including non-human primates, pigs and rodents have been used extensively to study the mechanisms of cardiovascular disease. However, there is an increasing desire for alternative model systems that provide excellent scientific value... Read More about Zebrafish as a tractable model of human cardiovascular disease.

Asymmetric Hapln1a drives regionalized cardiac ECM expansion and promotes heart morphogenesis in zebrafish development (2021)
Journal Article
Derrick, C. J., Sánchez-Posada, J., Hussein, F., Tessadori, F., Pollitt, E. J. G., Savage, A. M., …Noël, E. S. (2022). Asymmetric Hapln1a drives regionalized cardiac ECM expansion and promotes heart morphogenesis in zebrafish development. Cardiovascular Research, 118(1), 226-240. https://doi.org/10.1093/cvr/cvab004

Aims: Vertebrate heart development requires the complex morphogenesis of a linear tube to form the mature organ, a process essential for correct cardiac form and function, requiring coordination of embryonic laterality, cardiac growth, and regionaliz... Read More about Asymmetric Hapln1a drives regionalized cardiac ECM expansion and promotes heart morphogenesis in zebrafish development.

Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis (2020)
Journal Article
Farrugia, C., Stafford, G. P., Potempa, J., Wilkinson, R. N., Chen, Y., Murdoch, C., & Widziolek, M. (2021). Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis. FEBS Journal, 288(5), 1479-1495. https://doi.org/10.1111/febs.15486

Several studies have shown a clear association between periodontal disease and increased risk of cardiovascular disease. Porphyromonas gingivalis (Pg), a key oral pathogen, and its cell surface-expressed gingipains, induce oedema in a zebrafish larva... Read More about Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis.

Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish (2019)
Journal Article
Chhabria, K., Vouros, A., Gray, C., MacDonald, R. B., Jiang, Z., Wilkinson, R. N., …Chico, T. J. (2019). Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish. Disease Models and Mechanisms, 12(9), https://doi.org/10.1242/dmm.039867

Diabetes is associated with dysfunction of the neurovascular unit, although the mechanisms of this are incompletely understood and currently no treatment exists to prevent these negative effects. We previously found that the nitric oxide (NO) donor s... Read More about Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish.

Cerebrovascular endothelial cells form transient Notch?dependent cystic structures in zebrafish (2019)
Journal Article
Kugler, E. C., Lessen, M., Daetwyler, S., Chhabria, K., Savage, A. M., Silva, V., …Chico, T. J. (2019). Cerebrovascular endothelial cells form transient Notch‐dependent cystic structures in zebrafish. EMBO Reports, 20(8), https://doi.org/10.15252/embr.201847047

We identify a novel endothelial membrane behaviour in transgenic zebrafish. Cerebral blood vessels extrude large transient spherical structures that persist for an average of 23 min before regressing into the parent vessel. We term these structures "... Read More about Cerebrovascular endothelial cells form transient Notch?dependent cystic structures in zebrafish.

The role of endothelial cilia in postembryonic vascular development (2019)
Journal Article
Elworthy, S., Savage, A. M., Wilkinson, R. N., Malicki, J. J., & Chico, T. J. (2019). The role of endothelial cilia in postembryonic vascular development. Developmental Dynamics, 248(6), 410-425. https://doi.org/10.1002/dvdy.40

BACKGROUND: Cilia are essential for morphogenesis and maintenance of many tissues. Loss-of-function of cilia in early Zebrafish development causes a range of vascular defects, including cerebral hemorrhage and reduced arterial vascular mural cell co... Read More about The role of endothelial cilia in postembryonic vascular development.

TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells (2019)
Journal Article
Arhatte, M., Gunaratne, G. S., El Boustany, C., Kuo, I. Y., Moro, C., Duprat, F., …Patel, A. (2019). TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells. Nature Communications, 10(1), Article 2024. https://doi.org/10.1038/s41467-019-10045-y

Mutations in the polycystins cause autosomal dominant polycystic kidney disease (ADPKD). Here we show that transmembrane protein 33 (TMEM33) interacts with the ion channel polycystin-2 (PC2) at the endoplasmic reticulum (ER) membrane, enhancing its o... Read More about TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells.

tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis (2019)
Journal Article
Savage, A. M., Kurusamy, S., Chen, Y., Jiang, Z., Chhabria, K., MacDonald, R. B., …Wilkinson, R. N. (2019). tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis. Nature Communications, 10, Article 732. https://doi.org/10.1038/s41467-019-08590-7

Angiogenesis requires co-ordination of multiple signalling inputs to regulate the behaviour of endothelial cells (ECs) as they form vascular networks. Vascular endothelial growth factor (VEGF) is essential for angiogenesis and induces downstream sign... Read More about tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis.

Venous identity requires BMP signalling through ALK3 (2019)
Journal Article
Neal, A., Nornes, S., Payne, S., Wallace, M. D., Fritzsche, M., Louphrasitthiphol, P., …De Val, S. (2019). Venous identity requires BMP signalling through ALK3. Nature Communications, 10(1), 1-18. https://doi.org/10.1038/s41467-019-08315-w

Venous endothelial cells are molecularly and functionally distinct from their arterial counterparts. Although veins are often considered the default endothelial state, genetic manipulations can modulate both acquisition and loss of venous fate, sugge... Read More about Venous identity requires BMP signalling through ALK3.

The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish (2018)
Journal Article
Chhabria, K., Plant, K., Bandmann, O., Wilkinson, R. N., Martin, C., Kugler, E., …Howarth, C. (2020). The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish. Journal of Cerebral Blood Flow and Metabolism, 40(2), 298-313. https://doi.org/10.1177/0271678X18810615

Neurovascular coupling (through which local cerebral blood flow changes in response to neural activation are mediated) is impaired in many diseases including diabetes. Current preclinical rodent models of neurovascular coupling rely on invasive surge... Read More about The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish.

Gfi1aa and Gfi1b set the pace for primitive erythroblast differentiation from hemangioblasts in the zebrafish embryo (2018)
Journal Article
Moore, C., Richens, J. L., Hough, Y., Ucanok, D., Malla, S., Sang, F., …Gering, M. (2018). Gfi1aa and Gfi1b set the pace for primitive erythroblast differentiation from hemangioblasts in the zebrafish embryo. Blood Advances, 2(20), 2589-2606. https://doi.org/10.1182/bloodadvances.2018020156

The transcriptional repressors Gfi1(a) and Gfi1b are epigenetic regulators with unique and overlapping roles in hematopoiesis. In different contexts, Gfi1 and Gfi1b restrict or promote cell proliferation, prevent apoptosis, influence cell fate decisi... Read More about Gfi1aa and Gfi1b set the pace for primitive erythroblast differentiation from hemangioblasts in the zebrafish embryo.

Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion (2017)
Journal Article
Kurusamy, S., López-Maderuelo, D., Little, R., Cadagan, D., Savage, A. M., Ihugba, J. C., …Armesilla, A. L. (2017). Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion. Journal of Molecular and Cellular Cardiology, 109, 38-47. https://doi.org/10.1016/j.yjmcc.2017.07.001

Aims Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of... Read More about Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion.

A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis (2016)
Journal Article
Thambyrajah, R. S., Ucanok, D., Jalali, M., Hough, Y., Wilkinson, R. N., McMahon, K., …Gering, M. (2016). A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis. Developmental Biology, 417(1), 25-39. https://doi.org/10.1016/j.ydbio.2016.07.010

A transposon-mediated gene trap screen identified the zebrafish line qmc551 that expresses a GFP reporter in primitive erythrocytes and also in haemogenic endothelial cells, which give rise to haematopoietic stem and progenitor cells (HSPCs) that see... Read More about A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis.