Publications of Julien Hanson
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See detailDeciphering the role of the GPR101 orphan receptor in growth hormone hypersecretion
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Poster (2022, April)

Detailed reference viewed: 27 (1 ULiège)
See detailDeciphering the role of the GPR101 orphan receptor in growth hormone hypersecretion
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2022, February)

Detailed reference viewed: 21 (1 ULiège)
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See detailStructure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27
Pillaiyar, Thanigaimalai; Rosato, Francesca; Wozniak, Monika ULiege et al

in European Journal of Medicinal Chemistry (2021), 225

Detailed reference viewed: 32 (2 ULiège)
See detailDeciphering the role of the GPR101 orphan receptor in growth hormone hypersecretion
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Poster (2021, October)

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH secreting pituitary tumors over ... [more ▼]

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101(Trivellin et al, 2014). The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). We reported that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis (Abboud et al, 2020). Furthermore, we showed that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function. [less ▲]

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See detailNanoluciferase-based complementation assay to detect GPCR-G protein interaction
Laschet, Céline ULiege; Hanson, Julien ULiege

in Martins, Sofia; Prazeres, Duarte (Eds.) G Protein-Coupled Receptor Screening Assays - Methods in Molecular Biology (2021)

Detailed reference viewed: 43 (8 ULiège)
See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2021, April)

Detailed reference viewed: 17 (1 ULiège)
See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2021, April)

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See detailβ-arrestin2 recruitment at the β2 adrenergic receptor: a luciferase complementation assay adapted for undergraduate training in pharmacology
Ferraiolo, Mattia; Beckers, Pauline; Marquet, Nicolas et al

in Pharmacology Research and Perspectives (2021), 9(1),

In the context of pharmacology teaching, hands-on activities constitute an essential complement to theoretical lectures. Frequently, these activities consist in exposing fresh animal tissues or even ... [more ▼]

In the context of pharmacology teaching, hands-on activities constitute an essential complement to theoretical lectures. Frequently, these activities consist in exposing fresh animal tissues or even living animals to selected drugs and qualitatively or quantitatively evaluating functional responses. However, technological advancements in pharmacological research and the growing concerns for animal experimentation support the need for innovative and flexible in vitro assays adapted for teaching purposes. We herein report the implementation of a luciferase complementation assay enabling to dynamically monitor β-arrestin2 recruitment at the β2 adrenergic receptor in the framework of pharmacological training at the faculty of Pharmacy and Biomedical Sciences. The assay allowed students to quantitatively characterize the competitive antagonism of propranolol, and to calculate pEC50, pKB and pA2 values after a guided data-analysis session. Moreover, the newly implemented workshop delivered highly reproducible results and were generally appreciated by students. As such, we report that the luciferase complementation-based assay proved to be a straightforward, robust and cost-effective alternative to experiments performed on animal tissues, constituting a useful and flexible tool to enhance and update current hands-on training in the context of pharmacological teaching. [less ▲]

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See detailAlternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells.
Kerselidou, Despoina ULiege; Dohai, Bushra Saeed; Nelson, David R. et al

in Science Advances (2021), 7(19),

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of guanosine triphosphate nucleotides. Among posttranslational ... [more ▼]

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of guanosine triphosphate nucleotides. Among posttranslational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on the ER structure remains unclear. Here, we show that exostosin-1 (EXT1) glycosyltransferase, an enzyme involved in N-glycosylation, is a key regulator of ER morphology and dynamics. We have integrated multiomics and superresolution imaging to characterize the broad effect of EXT1 inactivation, including the ER shape-dynamics-function relationships in mammalian cells. We have observed that inactivating EXT1 induces cell enlargement and enhances metabolic switches such as protein secretion. In particular, suppressing EXT1 in mouse thymocytes causes developmental dysfunctions associated with the ER network extension. Last, our data illuminate the physical and functional aspects of the ER proteome-glycome-lipidome structure axis, with implications in biotechnology and medicine. [less ▲]

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See detailTHE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
Alexander, Stephen Ph; Christopoulos, Arthur; Davenport, Anthony P. et al

in British journal of pharmacology (2021), 178 Suppl 1

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 ... [more ▼]

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate. [less ▲]

Detailed reference viewed: 33 (1 ULiège)
See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2020, November)

Detailed reference viewed: 20 (1 ULiège)
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See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine ULiege et al

in Nature Communications (2020), 11(1), 4752

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over ... [more ▼]

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function. [less ▲]

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See detailNouvelles cibles et perspectives thérapeutiques. Vers une médecine de précision.
Hanson, Julien ULiege

in Revue Médicale de Liège (2020), 75(5-6), 460-465

A therapeutic target can be defined as the biochemical entity by which a drug exerts its beneficial effects. Historically, most drugs have been used without a precise knowledge of their mechanism of ... [more ▼]

A therapeutic target can be defined as the biochemical entity by which a drug exerts its beneficial effects. Historically, most drugs have been used without a precise knowledge of their mechanism of action. The rational drug design for a predefined target has been progressively implemented during the second half of the 20th century. Recent advances in genomics have accelerated the discovery of several targets involved in many pathologies. During the recent period, there has also been a diversification of the types of targets used in therapy. Generally, the proteins modulated by drugs belonged mainly to the families of membrane receptors (receptors coupled to G proteins, ion channels, etc.), nuclear receptors or enzymes. Technological advances in the field of therapeutic antibodies and biotechnologies enabled curative agents to reach previously undruggable targets. In this article, we review these trends and illustrate them by various examples, notably in the field of anticancer drugs, lipid-lowering drugs, gene therapy or antisense therapy. [less ▲]

Detailed reference viewed: 42 (1 ULiège)
See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2020)

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH secreting pituitary tumors over ... [more ▼]

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). We report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice. We also show that GPR101 promotes GH secretion through the activation of not only Gs, but also Gq/11, in a PKA and PKC-dependent manner, respectively. Interestingly, in stark contrast with other Gs-coupled receptors, GPR101 activation did not lead to the proliferation of somatotrope cells. These signatures of GPR101 signaling, notably PKC activation, are also present in human X-LAG pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function. [less ▲]

Detailed reference viewed: 31 (6 ULiège)
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See detailSomatostatin Analogue Resistance in McCune-Albright Syndrome
Vandevoorde, Stéphanie ULiege; Daly, Adrian ULiege; Hanson, Julien ULiege et al

Poster (2019, December)

McCune-Albright Syndrome (MAS) is a disorder characterized by involvement of multiple tissues, including skin, bone and endocrine glands. MAS is caused by post-zygotic mosaicism for GNAS gene mutations ... [more ▼]

McCune-Albright Syndrome (MAS) is a disorder characterized by involvement of multiple tissues, including skin, bone and endocrine glands. MAS is caused by post-zygotic mosaicism for GNAS gene mutations, which lead to a constitutively active form of the Gαs protein and increased cAMP levels. In the somatotropes of the pituitary, this increased cAMP leads to excessive growth hormone (GH) secretion. Somatostatin analogues (SSA), such as octreotide, that binds to somatostatin receptor SSTR2 are used in MAS patients to reduce GH secretion. However, MAS patients generally do not respond well to SSA, and GH control can rarely be achieved with SSA alone. In an in vitro model of MAS, five of the most common activating GNAS mutations lead to an increased level of cAMP, and a resistance to the treatment with SSA due to hyperactivated phosphokinase A. To further determine the underlying molecular causes of the SSA resistance, we studied the phosphorylation status of Filamin A (FLNA), a protein that couples somatostatin receptors to their cytoplasmic partners and to the cytoskeleton. Preliminary results suggest that three mutations of the GNAS gene may increase the phosphorylation status of FLNA. [less ▲]

Detailed reference viewed: 31 (4 ULiège)
See detailGPR101 orphan receptor in XLAG syndrome
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2019, December)

Detailed reference viewed: 17 (3 ULiège)
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See detailTHE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors
Alexander; Christopoulos, A; Davenport, AP et al

in British Journal of Pharmacology (2019), 176(Suppl 1), 21-141

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with ... [more ▼]

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate. [less ▲]

Detailed reference viewed: 64 (2 ULiège)