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Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity (2023)
Journal Article
Portelli, M. A., Bhaker, S., Pang, V., Bates, D. O., Johnson, S. R., Mazar, A. P., …Sayers, I. (2023). Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity. Clinical and Translational Allergy, 13(10), Article e12293. https://doi.org/10.1002/clt2.12293

AbstractBackgroundExpression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.Objective... Read More about Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity.

Targeting FGFRs Using PD173074 as a Novel Therapeutic Strategy in Cholangiocarcinoma (2023)
Journal Article
Balasubramanian, B., Yacqub-Usman, K., Venkatraman, S., Myint, K. Z., Juengsamarn, J., Sarkhampee, P., …Tohtong, R. (2023). Targeting FGFRs Using PD173074 as a Novel Therapeutic Strategy in Cholangiocarcinoma. Cancers, 15(9), Article 2528. https://doi.org/10.3390/cancers15092528

Cholangiocarcinoma (CCA) is an architecturally complex tumour with high heterogeneity. Discovery at later stages makes treatment challenging. However, the lack of early detection methodologies and the asymptomatic nature of CCA make early diagnosis m... Read More about Targeting FGFRs Using PD173074 as a Novel Therapeutic Strategy in Cholangiocarcinoma.

Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome (2022)
Journal Article
Sueca-Comes, M., Rusu, E. C., Grabowska, A. M., & Bates, D. O. (2022). Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome. Pharmacological Reviews, 74(4), 1136-1145. https://doi.org/10.1124/pharmrev.121.000410

The number of cancer drugs is increasing as new chemical entities are developed to target molecules, often protein kinases, driving cancer progression. In 2009, Fedorov et al. identified that of the protein kinases in the human kinome, most of the fo... Read More about Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome.

Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts (2022)
Journal Article
Sharpe, B. P., Hayden, A., Manousopoulou, A., Cowie, A., Walker, R. C., Harrington, J., …Underwood, T. J. (2022). Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts. Cell Reports Medicine, 3(6), Article 100541. https://doi.org/10.1016/j.xcrm.2022.100541

The chemotherapy resistance of esophageal adenocarcinomas (EACs) is underpinned by cancer cell extrinsic mechanisms of the tumor microenvironment (TME). We demonstrate that, by targeting the tumor-promoting functions of the predominant TME cell type,... Read More about Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts.

Apoptosis in Cancer Cells Is Induced by Alternative Splicing of hnRNPA2/B1 Through Splicing of Bcl-x, a Mechanism that Can Be Stimulated by an Extract of the South African Medicinal Plant, Cotyledon orbiculata (2020)
Journal Article
Makhafola, T. J., Mbele, M., Yacqub-Usman, K., Hendren, A., Haigh, D. B., Blackley, Z., …Dlamini, Z. (2020). Apoptosis in Cancer Cells Is Induced by Alternative Splicing of hnRNPA2/B1 Through Splicing of Bcl-x, a Mechanism that Can Be Stimulated by an Extract of the South African Medicinal Plant, Cotyledon orbiculata. Frontiers in Oncology, 10, Article 547392. https://doi.org/10.3389/fonc.2020.547392

Alternative splicing is deregulated in cancer and alternatively spliced products can be linked to cancer hallmarks. Targeting alternative splicing could offer novel effective cancer treatments. We investigated the effects of the crude extract of a So... Read More about Apoptosis in Cancer Cells Is Induced by Alternative Splicing of hnRNPA2/B1 Through Splicing of Bcl-x, a Mechanism that Can Be Stimulated by an Extract of the South African Medicinal Plant, Cotyledon orbiculata.

Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells (2020)
Journal Article
Boonsri, B., Yacqub-Usman, K., Thintharua, P., Myint, K. Z., Sae-Lao, T., Collier, P., …Wongprasert, K. (2020). Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells. Cancer Research and Treatment, 53(2), 457-470. https://doi.org/10.4143/crt.2020.585

Purpose The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in pati... Read More about Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells.

Non?invasive measurement of retinal permeability in a diabetic rat model (2020)
Journal Article
Whatmore, J. L., Allen, C. L., Malhi, N. K., Whatmore, J. D., Bates, D. O., & Arkill, K. P. (2020). Non?invasive measurement of retinal permeability in a diabetic rat model. Microcirculation, 27(6), https://doi.org/10.1111/micc.12623

Objective: The gold standard for measuring blood-retinal barrier permeability is the Evans blue assay. However, this technique has limitations in vivo, including non-specific tissue binding and toxicity. This study describes a non-toxic, high through... Read More about Non?invasive measurement of retinal permeability in a diabetic rat model.

Blocking endothelial apoptosis revascularises the retina in a model of ischemic retinopathy (2020)
Journal Article
Grant, Z. L., Whitehead, L., Wong, V. H. Y., He, Z., Yan, R. Y., Miles, A. R., …Coultas, L. (2020). Blocking endothelial apoptosis revascularises the retina in a model of ischemic retinopathy. Journal of Clinical Investigation, 130(8), 4235-4251. https://doi.org/10.1172/jci127668

Aberrant, neovascular retinal blood vessel growth is a vision-threatening complication in ischemic retinal diseases. It is driven by retinal hypoxia frequently caused by capillary nonperfusion and endothelial cell (EC) loss. We investigated the role... Read More about Blocking endothelial apoptosis revascularises the retina in a model of ischemic retinopathy.

Phenotypic and functional translation of IL33 genetics in asthma (2020)
Journal Article
Ketelaar, M. E., Portelli, M. A., Dijk, F. N., Shrine, N., Faiz, A., Vermeulen, C. J., …Nawijn, M. C. (2021). Phenotypic and functional translation of IL33 genetics in asthma. Journal of Allergy and Clinical Immunology, 147(1), 144-157. https://doi.org/10.1016/j.jaci.2020.04.051

© 2020 Background: Asthma is a complex disease with multiple phenotypes that may differ in disease pathobiology and treatment response. IL33 single nucleotide polymorphisms (SNPs) have been reproducibly associated with asthma. IL33 levels are elevate... Read More about Phenotypic and functional translation of IL33 genetics in asthma.

Local microvascular leakage promotes trafficking of activated neutrophils to remote organs (2020)
Journal Article
Owen-Woods, C., Joulia, R., Barkaway, A., Rolas, L., Ma, B., Nottebaum, A. F., …Nourshargh, S. (2020). Local microvascular leakage promotes trafficking of activated neutrophils to remote organs. Journal of Clinical Investigation, 130(5), 2301-2318. https://doi.org/10.1172/JCI133661

Copyright: © 2020, Owen-Woods et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmar... Read More about Local microvascular leakage promotes trafficking of activated neutrophils to remote organs.

Activation of Notch signalling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway (2019)
Journal Article
Boardman, R., Pang, V., Malhi, N., Lynch, A. P., Leach, L., Benest, A. V., …Machado, M. J. (2019). Activation of Notch signalling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway. AJP - Heart and Circulatory Physiology, 316(5), H1065-H1075. https://doi.org/10.1152/ajpheart.00610.2018

© 2019 the American Physiological Society. The Notch ligand delta-like ligand 4 (Dll4), upregulated by VEGF, is a key regulator of vessel morphogenesis and function, controlling tip and stalk cell selection during sprouting angiogenesis. Inhibition o... Read More about Activation of Notch signalling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway.

Enhanced notch signaling modulates unproductive revascularization in response to nitric oxide-angiopoietin signaling in a mouse model of peripheral ischemia (2019)
Journal Article
Machado, M. J., Boardman, R., Riu, F., Emanueli, C., Benest, A. V., & Bates, D. O. (2019). Enhanced notch signaling modulates unproductive revascularization in response to nitric oxide-angiopoietin signaling in a mouse model of peripheral ischemia. Microcirculation, 26(6), https://doi.org/10.1111/micc.12549

Introduction Arteriolargenesis can be induced by concomitant stimulation of nitric Oxide (NO)?Angiopoietin receptor (Tie)?Vascular Endothelial Growth Factor (VEGF) signaling in the rat mesentery angiogenesis assay. We hypothesized that the same comb... Read More about Enhanced notch signaling modulates unproductive revascularization in response to nitric oxide-angiopoietin signaling in a mouse model of peripheral ischemia.

An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance (2019)
Journal Article
Li, N., Babaei-Jadidi, R., Lorenzi, F., Spencer-Dene, B., Clarke, P., Domingo, E., …Nateri, A. S. (2019). An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance. Oncogenesis, 8, Article 13. https://doi.org/10.1038/s41389-019-0125-3

Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial–mesenchymal transition (EMT) process. Cu... Read More about An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance.

SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4 (2018)
Journal Article
Tzelepis, K., De Braekeleer, E., Aspris, D., Barbieri, I., Vijayabaskar, M. S., Liu, W., …Vassiliou, G. S. (2018). SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4. Nature Communications, 9(1), https://doi.org/10.1038/s41467-018-07620-0

We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonge... Read More about SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4.

VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy (2018)
Journal Article
Onions, K. L., Gamez, M., Buckner, N. R., Baker, S. L., Betteridge, K. B., Desideri, S., …Foster, R. R. (2019). VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy. Diabetes, 68(1), 172-187. https://doi.org/10.2337/db18-0045

Elevated levels of vascular endothelial growth factor (VEGF) A are thought to cause glomerular endothelial cell (GEnC) dysfunction and albuminuria in diabetic nephropathy. We hypothesized that VEGFC could counteract these effects of VEGFA to protect... Read More about VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy.

BDNF (Brain-Derived Neurotrophic Factor) Promotes Embryonic Stem Cells Differentiation to Endothelial Cells Via a Molecular Pathway, Including MicroRNA-214, EZH2 (Enhancer of Zeste Homolog 2), and eNOS (Endothelial Nitric Oxide Synthase) (2018)
Journal Article
Descamps, B., Saif, J., Benest, A. V., Biglino, G., Bates, D. O., Chamorro-Jorganes, A., & Emanueli, C. (2018). BDNF (Brain-Derived Neurotrophic Factor) Promotes Embryonic Stem Cells Differentiation to Endothelial Cells Via a Molecular Pathway, Including MicroRNA-214, EZH2 (Enhancer of Zeste Homolog 2), and eNOS (Endothelial Nitric Oxide Synthase). Arteriosclerosis, Thrombosis, and Vascular Biology, 38(9), 2117-2125. doi:10.1161/atvbaha.118.311400

Sensory neuronal sensitisation occurs through HMGB-1/RAGE and TRPV1 in high glucose conditions (2018)
Journal Article
Bestall, S. M., Hulse, R. P., Blackley, Z., Swift, M., Ved, N., Paton, K., …Donaldson, L. F. (in press). Sensory neuronal sensitisation occurs through HMGB-1/RAGE and TRPV1 in high glucose conditions. Journal of Cell Science, Article jcs.215939. https://doi.org/10.1242/jcs.215939

Many potential causes for painful diabetic neuropathy have been proposed including actions of cytokines and growth factors. High mobility group protein B1 (HMGB1) is a RAGE agonist, increased in diabetes, that contributes to pain by modulating periph... Read More about Sensory neuronal sensitisation occurs through HMGB-1/RAGE and TRPV1 in high glucose conditions.

Novel haemodynamic structures in the human glomerulus (2018)
Journal Article
Neal, C., Arkill, K., Bell, J., Betteridge, K., Bates, D., Winlove, C., …Harper, S. (in press). Novel haemodynamic structures in the human glomerulus. AJP - Renal Physiology, https://doi.org/10.1152/ajprenal.00566.2017

To investigate human glomerular structure under conditions of physiological perfusion we have analysed fresh and perfusion fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, conf... Read More about Novel haemodynamic structures in the human glomerulus.

Physiological Role of Vascular Endothelial Growth Factors as Homeostatic Regulators (2018)
Journal Article
Bates, D. O., Beazley-Long, N., Benest, A. V., Ye, X., Ved, N., Hulse, R. P., …Foster, R. R. (2018). Physiological Role of Vascular Endothelial Growth Factors as Homeostatic Regulators. Comprehensive Physiology, 8(3), 955-979. https://doi.org/10.1002/cphy.c170015

The vascular endothelial growth factor (VEGF) family of proteins are key regulators of physiological systems. Originally linked with endothelial function, they have since become understood to be principal regulators of multiple tissues, both through... Read More about Physiological Role of Vascular Endothelial Growth Factors as Homeostatic Regulators.

Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain (2018)
Journal Article
Ved, N., Da Vitoria Lobo, M., Bestall, S. M., Vidueira, C., Beazley-Long, N., Ballmer-Hofer, K., …Hulse, R. P. (2018). Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain. Journal of Physiology, 596(16), 3675-3693. https://doi.org/10.1113/JP275067

Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord a... Read More about Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain.

VEGFR2 promotes central endothelial activation and the spread of pain in inflammatory arthritis (2018)
Journal Article
Beazley-Long, N., Moss, C. E., Ashby, W. R., Bestall, S. M., Almahasneh, F., Durrant, A. M., …Donaldson, L. F. (2018). VEGFR2 promotes central endothelial activation and the spread of pain in inflammatory arthritis. Brain, Behavior, and Immunity, 74, 49-67. https://doi.org/10.1016/j.bbi.2018.03.012

Chronic pain can develop in response to conditions such as inflammatory arthritis. The central mechanisms underlying the development and maintenance of chronic pain in humans are not well elucidated although there is evidence for a role of microglia... Read More about VEGFR2 promotes central endothelial activation and the spread of pain in inflammatory arthritis.

Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury (2018)
Journal Article
Stevens, M., Neal, C. R., Salmon, A. H., Bates, D. O., Harper, S. J., & Oltean, S. (in press). Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury. Nephron, https://doi.org/10.1159/000485664

BACKGROUND/AIMS:Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon bindin... Read More about Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury.

Effects of hypoxia and hyperoxia on the differential expression of VEGF-A isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF) (2018)
Journal Article
Barratt, S. L., Blythe, T., Ourradi, K., Jarrett, C., Welsh, G. I., Bates, D. O., & Millar, A. B. (in press). Effects of hypoxia and hyperoxia on the differential expression of VEGF-A isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF). Respiratory Research, 19, https://doi.org/10.1186/s12931-017-0711-x

Dysregulation of VEGF-A bioavailability has been implicated in the development of lung injury/fibrosis, exemplified by Idiopathic Pulmonary Fibrosis (IPF). VEGF-A is a target of the hypoxic response via its translational regulation by HIF-1?. The rol... Read More about Effects of hypoxia and hyperoxia on the differential expression of VEGF-A isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF).

Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin (2017)
Journal Article
Pang, V., Bates, D. O., & Leach, L. (2017). Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin. Clinical Science, 131(23), 2763-2775. https://doi.org/10.1042/CS20171252

The human placenta nourishes and protects the developing fetus whilst influencing maternal physiology for fetal advantage. It expresses several members of the VEGF family including the pro-angiogenic/pro-permeability VEGF-A165a isoform, the anti-angi... Read More about Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin.

Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells (2017)
Journal Article
Sae-Lao, T., Luplertlop, N., Janvilisri, T., Tohtong, R., Bates, D. O., & Wongprasert, K. (2017). Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells. Phytomedicine, 36, https://doi.org/10.1016/j.phymed.2017.09.014

BACKGROUND: Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastati... Read More about Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells.

Differential expression of VEGF-Axxx isoforms is critical for development of pulmonary fibrosis (2017)
Journal Article
Barratt, S. L., Blythe, T., Jarrett, C., Ourradi, K., Shelley-Fraser, G., Day, M. J., …Millar, A. B. (2017). Differential expression of VEGF-Axxx isoforms is critical for development of pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 196(4), https://doi.org/10.1164/rccm.201603-0568OC

RATIONALE Fibrosis after lung injury is related to poor outcome, and idiopathic pulmonary fibrosis (IPF) can be regarded as an exemplar. Vascular endothelial growth factor (VEGF)-A has been implicated in this context, but there are conflicting rep... Read More about Differential expression of VEGF-Axxx isoforms is critical for development of pulmonary fibrosis.

VEGF-A165b protects against proteinuria in a mouse model with progressive depletion of all endogenous VEGF-A splice isoforms from the kidney (2017)
Journal Article
Stevens, M., Neal, C. R., Salmon, A. H., Bates, D. O., Harper, S. J., & Oltean, S. (2017). VEGF-A165b protects against proteinuria in a mouse model with progressive depletion of all endogenous VEGF-A splice isoforms from the kidney. Journal of Physiology, 595(19), 6281-6298. https://doi.org/10.1113/jp274481

Chronic kidney disease (CKD) is strongly associated with a decrease in the expression of VEGF-A. However, little is known about the contribution of VEGF-A splice isoforms to kidney physiology and pathology. Previous studies suggest that the splice is... Read More about VEGF-A165b protects against proteinuria in a mouse model with progressive depletion of all endogenous VEGF-A splice isoforms from the kidney.

The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1 (2017)
Journal Article
Pruszko, M., Milano, E., Forcato, M., Donzelli, S., Ganci, F., Di Agostino, S., …Fontemaggi, G. (in press). The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1. EMBO Reports, Article e201643370. https://doi.org/10.15252/embr.201643370

The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear... Read More about The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1.

Can the co-dependence of the immune system and angiogenesis facilitate pharmacological targeting of tumours? (2017)
Journal Article
Mortara, L., Benest, A. V., Bates, D. O., & Noonan, D. M. (2017). Can the co-dependence of the immune system and angiogenesis facilitate pharmacological targeting of tumours?. Current Opinion in Pharmacology, 35, 66-74. https://doi.org/10.1016/j.coph.2017.05.009

Tumours elicit a number of mechanisms to induce a reprogramming of innate and adaptive immune cells to their advantage, inducing a pro-angiogenic phenotype. Investigation of these events is now leading to the identification of specific myeloid and ly... Read More about Can the co-dependence of the immune system and angiogenesis facilitate pharmacological targeting of tumours?.

Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function (2017)
Journal Article
Betteridge, K., Arkill, K., Neal, C., Harper, S., Foster, B., Satchell, S., …Salmon, A. (2017). Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function. Journal of Physiology, 595(15), https://doi.org/10.1113/JP274167

The endothelial glycocalyx forms a continuous coat over the luminal surface of all vessels, and regulates multiple vascular functions. The contribution of individual components of the endothelial glycocalyx to one critical vascular function, microvas... Read More about Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function.

Sulfated galactans from red seaweed Gracilaria fisheri target epidermal growth factor receptor (EGFR) and inhibit cholangiocarcinoma cells (CCA) proliferation (2017)
Journal Article
Sae-lao, T., Tohtong, R., Bates, D. O., & Wongprasert, K. (2017). Sulfated galactans from red seaweed Gracilaria fisheri target epidermal growth factor receptor (EGFR) and inhibit cholangiocarcinoma cells (CCA) proliferation. American Journal of Chinese Medicine, 45(3), 615-633. https://doi.org/10.1142/S0192415X17500367

Cholangiocarcinoma (CCA) is increasing in incidence worldwide and is resistant to chemotherapeutic agents, making treatment of CCA a major challenge. Previous studies reported that natural sulfated polysaccharides (SPs) disrupted growth factor recept... Read More about Sulfated galactans from red seaweed Gracilaria fisheri target epidermal growth factor receptor (EGFR) and inhibit cholangiocarcinoma cells (CCA) proliferation.

Vascular endothelial growth factor-A165b ameliorates outer-retinal barrier and vascular dysfunction in the diabetic retina (2017)
Journal Article
Ved, N., Hulse, R. P., Bestall, S. M., Donaldson, L. F., Bainbridge, J. W., & Bates, D. O. (2017). Vascular endothelial growth factor-A165b ameliorates outer-retinal barrier and vascular dysfunction in the diabetic retina. Clinical Science, 131(12), 1225-1243. https://doi.org/10.1042/CS20170102

Diabetic retinopathy (DR) is one of the leading causes of blindness in the developed world. Characteristic features of DR are retinal neurodegeneration, pathological angiogenesis and breakdown of both the inner and outer retinal barriers of the retin... Read More about Vascular endothelial growth factor-A165b ameliorates outer-retinal barrier and vascular dysfunction in the diabetic retina.

Mechanisms regulating angiogenesis underlie seasonal control of pituitary function (2017)
Journal Article
Castle-Miller, J., Bates, D. O., & Tortonese, D. J. (2017). Mechanisms regulating angiogenesis underlie seasonal control of pituitary function. Proceedings of the National Academy of Sciences, 114(12), E2514-E2523. https://doi.org/10.1073/pnas.1618917114

Seasonal changes in mammalian physiology, such as those affecting reproduction, hibernation and metabolism, are controlled by pituitary hormones released in response to annual environmental changes. In temperate zones, the primary environmental cue d... Read More about Mechanisms regulating angiogenesis underlie seasonal control of pituitary function.

Development of potent, selective SRPK1 inhibitors as potential topical therapeutics for neovascular eye disease (2017)
Journal Article
Batson, J., Toop, H. D., Redondo, C., Babaei-Jadidi, R., Chaikaud, A., Wearmouth, S. F., …Morris, J. C. (2017). Development of potent, selective SRPK1 inhibitors as potential topical therapeutics for neovascular eye disease. ACS Chemical Biology, 12(3), 825-832. https://doi.org/10.1021/acschembio.6b01048

Serine/arginine-protein kinase 1 (SRPK1) regulates alternative splicing of VEGF-A to pro-angiogenic isoforms and SRPK1 inhibition can restore the balance of pro/antiangiogenic isoforms to normal physiological levels. The lack of potency and selectivi... Read More about Development of potent, selective SRPK1 inhibitors as potential topical therapeutics for neovascular eye disease.

Differential regulation of blood flow induced neovascularisation and mural cell recruitment by VEGF and angiopoietin signaling (2017)
Journal Article
Stone, O. A., Carter, J. G., Lin, P. C., Paleolog, E., Machado, M. J. C., & Bates, D. O. (2017). Differential regulation of blood flow induced neovascularisation and mural cell recruitment by VEGF and angiopoietin signaling. Journal of Physiology, 595(5), 1575-1591. https://doi.org/10.1113/JP273430

Signalling through VEGF receptors and the Tie2 receptor by angiopoietins is required in combination with blood flow for the formation of a functional vascular network. We tested the hypothesis that VEGF and Ang1 contribute differentially to neovascul... Read More about Differential regulation of blood flow induced neovascularisation and mural cell recruitment by VEGF and angiopoietin signaling.

Pharmacology of modulators of alternative splicing (2017)
Journal Article
Bates, D. O., Morris, J. C., Oltean, S., & Donaldson, L. F. (2017). Pharmacology of modulators of alternative splicing. Pharmacological Reviews, 69(1), https://doi.org/10.1124/pr.115.011239

More than 95% of genes in the human genome are alternatively spliced to form multiple transcripts, often encoding proteins with differing or opposing function. The control of alternative splicing is now being elucidated, and with this comes the oppor... Read More about Pharmacology of modulators of alternative splicing.

The control of alternative splicing by SRSF1 in myelinated afferents contributes to the development of neuropathic pain (2016)
Journal Article
Hulse, R. P., Drake, R. A., Bates, D. O., & Donaldson, L. F. (in press). The control of alternative splicing by SRSF1 in myelinated afferents contributes to the development of neuropathic pain. Neurobiology of Disease, 96, https://doi.org/10.1016/j.nbd.2016.09.009

Neuropathic pain results from neuroplasticity in nociceptive neuronal networks. Here we demonstrate that control of alternative pre-mRNA splicing, through the splice factor serine-arginine splice factor 1 (SRSF1), is integral to the processing of noc... Read More about The control of alternative splicing by SRSF1 in myelinated afferents contributes to the development of neuropathic pain.

Altered ratios of pro- and anti-angiogenic VEGF-A variants and pericyte expression of DLL4 disrupt the vascular maturation in infantile haemangioma (2016)
Journal Article
Ye, X., Abou-Rayyah, Y., Bischoff, J., Ritchie, A., Sebire, N. J., Watts, P., …Bates, D. O. (in press). Altered ratios of pro- and anti-angiogenic VEGF-A variants and pericyte expression of DLL4 disrupt the vascular maturation in infantile haemangioma. Journal of Pathology, 239(2), https://doi.org/10.1002/path.4715

Infantile haemangioma (IH), the most common neoplasm in infants, is a slowly resolving vascular tumour. Vascular endothelial growth factor A (VEGF-A), which consists of both the pro- and anti-angiogenic variants, contributes to the pathogenesis of IH... Read More about Altered ratios of pro- and anti-angiogenic VEGF-A variants and pericyte expression of DLL4 disrupt the vascular maturation in infantile haemangioma.

Direct detection and measurement of wall shear stress using a filamentous bio-nanoparticle (2015)
Journal Article
Salmon, A. H. J., Lobo, D. P., Wemyss, A. M., Smith, D. J., Straube, A., Betteridge, K. B., …Arkill, K. P. (2015). Direct detection and measurement of wall shear stress using a filamentous bio-nanoparticle. Nano Research, 8(10), 3307-3315. https://doi.org/10.1007/s12274-015-0831-x

The wall shear stress (WSS) that a moving fluid exerts on a surface affects many processes including those relating to vascular function. WSS plays an important role in normal physiology (e.g. angiogenesis) and affects the microvasculature's primary... Read More about Direct detection and measurement of wall shear stress using a filamentous bio-nanoparticle.

Vascular endothelial growth factor-A165b is protective and restores endothelial glycocalyx in diabetic nephropathy (2015)
Journal Article
Oltean, S., Qiu, Y., Ferguson, J. K., Stevens, M., Neal, C., Russell, A., …Salmon, A. H. (2015). Vascular endothelial growth factor-A165b is protective and restores endothelial glycocalyx in diabetic nephropathy. Journal of the American Society of Nephrology, 26(8), https://doi.org/10.1681/ASN.2014040350

Diabetic nephropathy is the leading cause of ESRD in high-income countries and a growing problem across the world. Vascular endothelial growth factor-A (VEGF-A) is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, yet... Read More about Vascular endothelial growth factor-A165b is protective and restores endothelial glycocalyx in diabetic nephropathy.

Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration (2015)
Journal Article
Hulse, R. P., Beazley-Long, N., Ved, N., Bestall, S. M., Riaz, H., Singhal, P., …Donaldson, L. F. (2015). Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration. Clinical Science, 129(8), https://doi.org/10.1042/CS20150124

Diabetic peripheral neuropathy affects up to half of diabetic patients. This neuronal damage leads to sensory disturbances, including allodynia and hyperalgesia. Many growth factors have been suggested as useful treatments for prevention of neurodege... Read More about Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration.

IL-4 Regulates Specific Arg-1+ Macrophage sFlt-1–Mediated Inhibition of Angiogenesis (2015)
Journal Article
Wu, W., Georgiadis, A., Copland, D. A., Liyanage, S., Luhmann, U. F., Robbie, S. J., …Dick, A. D. (2015). IL-4 Regulates Specific Arg-1+ Macrophage sFlt-1–Mediated Inhibition of Angiogenesis. American Journal of Pathology, 185(8), 2324-2335. https://doi.org/10.1016/j.ajpath.2015.04.013

One of the main drivers for neovascularization in age-related macular degeneration is activation of innate immunity in the presence of macrophages. Here, we demonstrate that T helper cell type 2 cytokines and, in particular, IL-4 condition human and... Read More about IL-4 Regulates Specific Arg-1+ Macrophage sFlt-1–Mediated Inhibition of Angiogenesis.

Regulation of vascular endothelial growth factor in prostate cancer (2015)
Journal Article
de Brot, S., Ntekim, A., Cardenas, R., James, V., Allegrucci, C., Heery, D. M., …Mongan, N. P. (2015). Regulation of vascular endothelial growth factor in prostate cancer. Endocrine-Related Cancer, 22(3), Article R107-R123. https://doi.org/10.1530/ERC-15-0123

Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to ?30% will experience local recurrence or metast... Read More about Regulation of vascular endothelial growth factor in prostate cancer.

Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer (2014)
Journal Article
Mavrou, A., Brakspear, K., Hamdollah-Zadeh, M., Damodaran, G., Babaei-Jadidi, R., Oxley, J., …Oltean, S. (2015). Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer. Oncogene, 34(33), 4311-4319. https://doi.org/10.1038/onc.2014.360

Angiogenesis is required for tumour growth and is induced principally by vascular endothelial growth factor A (VEGF-A). VEGF-A pre-mRNA is alternatively spliced at the terminal exon to produce two families of isoforms, pro- and anti-angiogenic, only... Read More about Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer.

Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia (2014)
Journal Article
Hulse, R., Beazley-Long, N., Hua, J., Kennedy, H., Prager, J., Bevan, H., …Donaldson, L. (2014). Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia. Neurobiology of Disease, 71, 245-259. https://doi.org/10.1016/j.nbd.2014.08.012

Vascular endothelial growth factor-A (VEGF-A) is best known as a key regulator of the formation of new blood vessels. Neutralization of VEGF-A with anti-VEGF therapy e.g. bevacizumab, can be painful, and this is hypothesized to result from a loss of... Read More about Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia.

Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance (2014)
Journal Article
Hamdollah Zadeh, M. A., Amin, E. M., Hoareau-Aveilla, C., Domingo, E., Symonds, K. E., Ye, X., …Bates, D. O. (2015). Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance. Molecular Oncology, 9(1), 167-178. https://doi.org/10.1016/j.molonc.2014.07.017

Antiangiogenic actions of vascular endothelial growth factor-A165b, an inhibitory isoform of vascular endothelial growth factor-A, in human obesity (2014)
Journal Article
Bates, D., Ngo, D. T. M., Farb, M. G., Kikuchi, R., Karki, S., Tiwari, S., …Gokce, N. (2014). Antiangiogenic actions of vascular endothelial growth factor-A165b, an inhibitory isoform of vascular endothelial growth factor-A, in human obesity. Circulation, 130(13), 1072-1080. https://doi.org/10.1161/CIRCULATIONAHA.113.008171

Background—Experimental studies suggest that visceral adiposity and adipose tissue dysfunction play a central role in obesity-related cardiometabolic complications. Impaired angiogenesis in fat has been implicated in the development of adipose tissue... Read More about Antiangiogenic actions of vascular endothelial growth factor-A165b, an inhibitory isoform of vascular endothelial growth factor-A, in human obesity.

Resolution of the three dimensional structure of components of the glomerular filtration barrier (2014)
Journal Article
Qvortrup, K., ARKILL, K., Starborg, T., Mantell, J., Knupp, C., Michel, C., …Neal, C. (2014). Resolution of the three dimensional structure of components of the glomerular filtration barrier. BMC Nephrology, 15(1), Article 24. https://doi.org/10.1186/1471-2369-15-24

Background: The human glomerulus is the primary filtration unit of the kidney, and contains the Glomerular Filtration Barrier (GFB). The GFB had been thought to comprise 3 layers - the endothelium, the basement membrane and the podocyte foot processe... Read More about Resolution of the three dimensional structure of components of the glomerular filtration barrier.

VEGF-A165b Is an Endogenous Neuroprotective Splice Isoform of Vascular Endothelial Growth Factor A inVivo and inVitro (2013)
Journal Article
Beazley-Long, N., Hua, J., Jehle, T., Hulse, R. P., Dersch, R., Lehrling, C., …Donaldson, L. F. (2013). VEGF-A165b Is an Endogenous Neuroprotective Splice Isoform of Vascular Endothelial Growth Factor A inVivo and inVitro. American Journal of Pathology, 183(3), 918-929. https://doi.org/10.1016/j.ajpath.2013.05.031

Vascular endothelial growth factor (VEGF) A is generated as two isoform families by alternative RNA splicing, represented by VEGF-A165a and VEGF-A165b. These isoforms have opposing actions on vascular permeability, angiogenesis, and vasodilatation. T... Read More about VEGF-A165b Is an Endogenous Neuroprotective Splice Isoform of Vascular Endothelial Growth Factor A inVivo and inVitro.