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Article: Therapeutic activation of G protein-coupled estrogen receptor 1 in Waldenström Macroglobulinemia.

Morelli, Eugenio / Hunter, Zachary R / Fulciniti, Mariateresa / Gullà, Annamaria / Perrotta, Ida Daniela / Zuccalà, Valeria / Federico, Cinzia / Juli, Giada / Manzoni, Martina / Ronchetti, Domenica / Romeo, Enrica / Gallo Cantafio, Maria Eugenia / Soncini, Debora / Maltese, Lorenza / Rossi, Marco / Roccaro, Aldo M / Cea, Michele / Tassone, Pierfrancesco / Neri, Antonino /

Treon, Steven C / Munshi, Nikhil C / Viglietto, Giuseppe / Amodio, Nicola

Experimental hematology & oncology

2022 Volume 11, Issue 1, Page(s) 54

Abstract: Activating G protein-coupled estrogen receptor 1 (GPER1) is an attractive therapeutic strategy ... to normal B cells. Using the clinically applicable GPER1-selective small-molecule agonist G-1 (also named ... agonist G-1. ...

Abstract	Activating G protein-coupled estrogen receptor 1 (GPER1) is an attractive therapeutic strategy for treating a variety of human diseases including cancer. Here, we show that GPER1 is significantly upregulated in tumor cells from different cohorts of Waldenström Macroglobulinemia (WM) patients compared to normal B cells. Using the clinically applicable GPER1-selective small-molecule agonist G-1 (also named Tespria), we found that pharmacological activation of GPER1 leads to G2/M cell cycle arrest and apoptosis both in vitro and in vivo in animal models, even in the context of the protective bone marrow milieu. Activation of GPER1 triggered the TP53 pathway, which remains actionable during WM progression. Thus, this study identifies a novel therapeutic target in WM and paves the way for the clinical development of the GPER1 agonist G-1.
Language	English
Publishing date	2022-09-12
Publishing country	England
Document type	Letter
ZDB-ID	2669066-4
ISSN	2162-3619
ISSN	2162-3619
DOI	10.1186/s40164-022-00305-x
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Article ; Online: Why Not Use the Immunoglobulin G

Russell, Alyce C / Kepka, Agnieszka / Trbojević-Akmačić, Irena / Ugrina, Ivo / Song, Manshu / Hui, Jennie / Hunter, Michael / Laws, Simon M / Lauc, Gordan / Wang, Wei

Omics : a journal of integrative biology

2019 Volume 23, Issue 12, Page(s) 668–670

MeSH term(s)	Absorptiometry, Photon ; Biomarkers/metabolism ; Female ; Glycosylation ; Humans ; Immunoglobulin G/metabolism ; Male ; Multivariate Analysis ; Polysaccharides/metabolism
Chemical Substances	Biomarkers ; Immunoglobulin G ; Polysaccharides
Language	English
Publishing date	2019-10-25
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2019.0155
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Article: Engineered biosynthesis of bacteriochlorophyll g

Ortega-Ramos, Marcia / Canniffe, Daniel P / Radle, Matthew I / Neil Hunter, C / Bryant, Donald A / Golbeck, John H

Biochimica et biophysica acta. Bioenergetics

2018 Volume 1859, Issue 7, Page(s) 501–509

Abstract: ... bacteriochlorophyll (BChl) g, which absorbs in the near-infrared region of the spectrum. Like the more common BChls ... a and b, BChl g is a true bacteriochlorin. It carries characteristic C3-vinyl and C8-ethylidene groups ... as the platform into which the engineered production of BChl g ...

Abstract	Engineering photosynthetic bacteria to utilize a heterologous reaction center that contains a different (bacterio) chlorophyll could improve solar energy conversion efficiency by allowing cells to absorb a broader range of the solar spectrum. One promising candidate is the homodimeric type I reaction center from Heliobacterium modesticaldum. It is the simplest known reaction center and uses bacteriochlorophyll (BChl) g, which absorbs in the near-infrared region of the spectrum. Like the more common BChls a and b, BChl g is a true bacteriochlorin. It carries characteristic C3-vinyl and C8-ethylidene groups, the latter shared with BChl b. The purple phototrophic bacterium Rhodobacter (Rba.) sphaeroides was chosen as the platform into which the engineered production of BChl g
MeSH term(s)	Bacteriochlorophylls/biosynthesis ; Biosynthetic Pathways ; Photosynthesis ; Polyisoprenyl Phosphates/biosynthesis ; Rhodobacter sphaeroides/genetics ; Rhodobacter sphaeroides/metabolism
Chemical Substances	Bacteriochlorophylls ; Polyisoprenyl Phosphates ; geranylgeranyl pyrophosphate (N21T0D88LX)
Language	English
Publishing date	2018-02-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0005-2728 ; 0006-3002 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0005-2728 ; 0006-3002 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbabio.2018.02.006
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Article ; Online: Type 2 Diabetes Mellitus is Associated with the Immunoglobulin G N-Glycome through Putative Proinflammatory Mechanisms in an Australian Population.

Li, Xingang / Wang, Hao / Russell, Alyce / Cao, Weijie / Wang, Xueqing / Ge, Siqi / Zheng, Yulu / Guo, Zheng / Hou, Haifeng / Song, Manshu / Yu, Xinwei / Wang, Youxin / Hunter, Michael / Roberts, Peter / Lauc, Gordan / Wang, Wei

Omics : a journal of integrative biology

2019 Volume 23, Issue 12, Page(s) 631–639

Abstract: ... immunoglobulin G (IgG) N-glycan patterns, T2DM, and their clinical risk factors in an Australian population. N ...

Abstract	Type 2 diabetes mellitus (T2DM) is a common complex trait arising from interactions among multiple environmental, genomic, and postgenomic factors. We report here the first attempt to investigate the association between immunoglobulin G (IgG) N-glycan patterns, T2DM, and their clinical risk factors in an Australian population. N-glycosylation of proteins is one of the most frequently observed co- and post-translational modifications, reflecting, importantly, the real-time status of the interplay between the genomic and postgenomic factors. In a community-based case-control study, 849 participants (217 cases and 632 controls) were recruited from an urban community in Busselton, Western Australia. We applied the ultraperformance liquid chromatography method to analyze the composition of IgG N-glycans. We then conducted Spearman's correlation analyses to explore the association between glycan biomarker candidates and clinical risk factors. We performed area under the curve (AUC) analysis of the receiver operating characteristic curves by fivefold cross-validation for clinical risk factors, IgG glycans, and their combination. Two directly measured and four derived glycan peaks were significantly associated with T2DM, after correction for extensive clinical confounders and false discovery rate, thus suggesting that IgG N-glycan traits are highly correlated with T2DM clinical risk factors. Moreover, adding the IgG glycan profiles to fasting blood glucose in the logistic regression model increased the AUC from 0.799 to 0.859. The AUC for IgG glycans alone was 0.623 with a 95% confidence interval 0.580-0.666. In addition, our study provided new evidence of diversity in T2DM complex trait by IgG N-glycan stratification. Six IgG glycan traits were firmly associated with T2DM, which reflects an increased proinflammatory and biological aging status. In summary, our study reports novel associations between the IgG N-glycome and T2DM in an Australian population and the putative role of proinflammatory mechanisms. Furthermore, IgG N-glycomic alterations offer future prospects as inflammatory biomarker candidates for T2DM diagnosis, and monitoring of T2DM progression to cardiovascular disease or renal failure.
MeSH term(s)	Aged ; Australia ; Biomarkers/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Female ; Glycosylation ; Humans ; Immunoglobulin G/metabolism ; Logistic Models ; Male ; Middle Aged ; Polysaccharides/metabolism ; Risk Factors
Chemical Substances	Biomarkers ; Immunoglobulin G ; Polysaccharides
Language	English
Publishing date	2019-09-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2019.0075
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Article ; Online: Identification of Immunoglobulin G Autoantibody Against Malondialdehyde-Acetaldehyde Adducts as a Novel Serological Biomarker for Ulcerative Colitis.

Duryee, Michael J / Ahmad, Rizwan / Eichele, Derrick D / Hunter, Carlos D / Mitra, Ananya / Talmon, Geoffrey A / Singh, Shailender / Smith, Lynette M / Rosen, Michael J / Dhawan, Punita / Thiele, Geoffrey M / Singh, Amar B

Clinical and translational gastroenterology

2022 Volume 13, Issue 4, Page(s) e00469

Abstract: ... the sensitivity and specificity.: Results: The MAA and blood immunoglobulin G (IgG) anti-MAA antibody levels were significantly ...

Abstract	Introduction: Inflammatory bowel disease (IBD) is associated with immune responses with oxidative stress wherein high levels of malondialdehyde result in the formation of a highly stable and immunogenic malondialdehyde-acetaldehyde adduct (MAA). Thus, this study evaluated the status of MAA and anti-MAA antibody isotypes in IBD and their potential as novel serological biomarkers for differentiating ulcerative colitis (UC) from Crohn's disease (CD). Methods: Levels of MAA and anti-MAA antibodies were examined in patients with IBD (171), non-IBD gastrointestinal diseases (77), and controls (83) from 2 independent cohorts using immunohistochemistry and enzyme-linked immunosorbent assay. Receiver operating characteristic curves and Youden cutoff index from logistic regression were used to determine the sensitivity and specificity. Results: The MAA and blood immunoglobulin G (IgG) anti-MAA antibody levels were significantly elevated in IBD compared with non-IBD patients (P = 0.0008) or controls (P = 0.02). Interestingly, patients with UC showed higher levels of IgG anti-MAA (P < 0.0001) than patients with CD including those with colonic CD (P = 0.0067). The odds ratio by logistic regression analysis predicted stronger association of IgG anti-MAA antibody with UC than CD. Subsequent analysis showed that IgG anti-MAA antibody levels could accurately identify (P = 0.0004) UC in the adult cohort with a sensitivity of 75.3% and a specificity of 71.4% and an area under the curve of 0.8072 (0.7121-0.9024). The pediatric cohort also showed an area under the curve of 0.8801 (0.7988-0.9614) and precisely distinguished (P < 0.0001) UC with sensitivity (95.8%) and specificity (72.3%). Discussion: Circulating IgG anti-MAA antibody levels can serve as a novel, noninvasive, and highly sensitive test to identify patients with UC and possibly differentiate them from patients with CD.
MeSH term(s)	Acetaldehyde ; Adult ; Autoantibodies ; Biomarkers ; Child ; Colitis, Ulcerative ; Crohn Disease ; Humans ; Immunoglobulin G ; Inflammatory Bowel Diseases ; Malondialdehyde
Chemical Substances	Autoantibodies ; Biomarkers ; Immunoglobulin G ; Malondialdehyde (4Y8F71G49Q) ; Acetaldehyde (GO1N1ZPR3B)
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2581516-7
ISSN	2155-384X ; 2155-384X
ISSN (online)	2155-384X
ISSN	2155-384X
DOI	10.14309/ctg.0000000000000469
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Article ; Online: Increased central adiposity is associated with pro-inflammatory immunoglobulin G N-glycans.

Russell, Alyce C / Kepka, Agnieszka / Trbojević-Akmačić, Irena / Ugrina, Ivo / Song, Manshu / Hui, Jennie / Hunter, Michael / Laws, Simon M / Lauc, Gordan / Wang, Wei

Immunobiology

2018 Volume 224, Issue 1, Page(s) 110–115

Abstract: ... Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation ... immunoglobulin G N-glycans.: Aim: We aimed to determine the association between increased body fat and ... the immunoglobulin G glycosylation features, comparing body mass index to other measures of body fat distribution ...

Abstract	Background: Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans. Aim: We aimed to determine the association between increased body fat and the immunoglobulin G glycosylation features, comparing body mass index to other measures of body fat distribution. Methods: We investigated a sample of 637 community-based 45-69 year olds, with mixed phenotypes, residing in Busselton, Western Australia. Body mass index and the waist-to-hip and waist-to-height ratios were calculated using anthropometry, while dual-energy x-ray absorptiometry was performed to gain an accurate measure of total and area specific body fat. Serum immunoglobulin GN-glycans were analysed by ultra-performance liquid chromatography. Results: Twenty-two N-glycan peaks were found to be associated with at least one of the fat measures. While the previous association of body mass index to agalactosylated immunoglobulin G was replicated, measures of central adiposity explained the most variation in the immunoglobulin G glycome. Conclusion: Central adiposity is associated with an increased pro-inflammatory fraction of immunoglobulin G, suggesting that the android/gynoid ratio or waist-to-height ratio instead be considered when controlling for adiposity in immunoglobulin G glycome biomarker studies.
MeSH term(s)	Absorptiometry, Photon ; Adipose Tissue/diagnostic imaging ; Adiposity/physiology ; Aged ; Anthropometry ; Australia/epidemiology ; Body Mass Index ; Chromatography, Liquid ; Community-Based Participatory Research ; Female ; Glycosylation ; Humans ; Immunoglobulin G/chemistry ; Immunoglobulin G/metabolism ; Inflammation Mediators/chemistry ; Inflammation Mediators/metabolism ; Male ; Middle Aged ; Obesity/epidemiology ; Risk Factors
Chemical Substances	Immunoglobulin G ; Inflammation Mediators
Language	English
Publishing date	2018-10-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	563292-4
ISSN	1878-3279 ; 0171-2985
ISSN (online)	1878-3279
ISSN	0171-2985
DOI	10.1016/j.imbio.2018.10.002
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Article ; Online: SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK).

Asquith, Christopher R M / Berger, Benedict-Tilman / Wan, Jing / Bennett, James M / Capuzzi, Stephen J / Crona, Daniel J / Drewry, David H / East, Michael P / Elkins, Jonathan M / Fedorov, Oleg / Godoi, Paulo H / Hunter, Debra M / Knapp, Stefan / Müller, Susanne / Torrice, Chad D / Wells, Carrow I / Earp, H Shelton / Willson, Timothy M / Zuercher, William J

Journal of medicinal chemistry

2019 Volume 62, Issue 5, Page(s) 2830–2836

Abstract: We describe SGC-GAK-1 (11), a potent, selective, and cell-active inhibitor of cyclin G-associated ...

Abstract	We describe SGC-GAK-1 (11), a potent, selective, and cell-active inhibitor of cyclin G-associated kinase (GAK), together with a structurally related negative control SGC-GAK-1N (14). 11 was highly selective in an in vitro kinome-wide screen, but cellular engagement assays defined RIPK2 as a collateral target. We identified 18 as a potent RIPK2 inhibitor lacking GAK activity. Together, this chemical probe set can be used to interrogate GAK cellular biology.
MeSH term(s)	Cyclin G/metabolism ; HEK293 Cells ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Molecular Probes/metabolism ; Protein-Serine-Threonine Kinases/metabolism
Chemical Substances	Cyclin G ; Intracellular Signaling Peptides and Proteins ; Molecular Probes ; GAK protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2019-02-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.8b01213
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Article ; Online: Conserved associations between G-quadruplex-forming DNA motifs and virulence gene families in malaria parasites.

Gage, Hunter L / Merrick, Catherine J

BMC genomics

2020 Volume 21, Issue 1, Page(s) 236

Abstract: ... diversification appear to be promoted by G-quadruplex (G4) DNA motifs, which are strongly associated with var ...

Abstract	Background: The Plasmodium genus of malaria parasites encodes several families of antigen-encoding genes. These genes tend to be hyper-variable, highly recombinogenic and variantly expressed. The best-characterized family is the var genes, exclusively found in the Laveranian subgenus of malaria parasites infecting humans and great apes. Var genes encode major virulence factors involved in immune evasion and the maintenance of chronic infections. In the human parasite P. falciparum, var gene recombination and diversification appear to be promoted by G-quadruplex (G4) DNA motifs, which are strongly associated with var genes in P. falciparum. Here, we investigated how this association might have evolved across Plasmodium species - both Laverania and also more distantly related species which lack vars but encode other, more ancient variant gene families. Results: The association between var genes and G4-forming motifs was conserved across Laverania, spanning ~ 1 million years of evolutionary time, with suggestive evidence for evolution of the association occurring within this subgenus. In rodent malaria species, G4-forming motifs were somewhat associated with pir genes, but this was not conserved in the Laverania, nor did we find a strong association of these motifs with any gene family in a second outgroup of avian malaria parasites. Secondly, we compared two different G4 prediction algorithms in their performance on extremely A/T-rich Plasmodium genomes, and also compared these predictions with experimental data from G4-seq, a DNA sequencing method for identifying G4-forming motifs. We found a surprising lack of concordance between the two algorithms and also between the algorithms and G4-seq data. Conclusions: G4-forming motifs are uniquely strongly associated with Plasmodium var genes, suggesting a particular role for G4s in recombination and diversification of these genes. Secondly, in the A/T-rich genomes of Plasmodium species, the choice of prediction algorithm may be particularly influential when studying G4s in these important protozoan pathogens.
MeSH term(s)	Animals ; G-Quadruplexes ; Malaria/parasitology ; Nucleotide Motifs ; Phylogeny ; Plasmodium/classification ; Plasmodium/genetics ; Plasmodium/pathogenicity ; Protozoan Proteins/genetics ; Virulence/genetics
Chemical Substances	Protozoan Proteins ; erythrocyte membrane protein 1, Plasmodium falciparum
Language	English
Publishing date	2020-03-17
Publishing country	England
Document type	Journal Article
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/s12864-020-6625-x
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Article ; Online: Native phasing of x-ray free-electron laser data for a G protein-coupled receptor.

Batyuk, Alexander / Galli, Lorenzo / Ishchenko, Andrii / Han, Gye Won / Gati, Cornelius / Popov, Petr A / Lee, Ming-Yue / Stauch, Benjamin / White, Thomas A / Barty, Anton / Aquila, Andrew / Hunter, Mark S / Liang, Mengning / Boutet, Sébastien / Pu, Mengchen / Liu, Zhi-Jie / Nelson, Garrett / James, Daniel / Li, Chufeng /

Zhao, Yun / Spence, John C H / Liu, Wei / Fromme, Petra / Katritch, Vsevolod / Weierstall, Uwe / Stevens, Raymond C / Cherezov, Vadim

Science advances

2016 Volume 2, Issue 9, Page(s) e1600292

Abstract: Serial femtosecond crystallography (SFX) takes advantage of extremely bright and ultrashort pulses produced by x-ray free-electron lasers (XFELs), allowing for the collection of high-resolution diffraction intensities from micrometer-sized crystals at ... ...

Abstract	Serial femtosecond crystallography (SFX) takes advantage of extremely bright and ultrashort pulses produced by x-ray free-electron lasers (XFELs), allowing for the collection of high-resolution diffraction intensities from micrometer-sized crystals at room temperature with minimal radiation damage, using the principle of "diffraction-before-destruction." However, de novo structure factor phase determination using XFELs has been difficult so far. We demonstrate the ability to solve the crystallographic phase problem for SFX data collected with an XFEL using the anomalous signal from native sulfur atoms, leading to a bias-free room temperature structure of the human A
Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.1600292
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Article ; Online: Urea-derived graphitic carbon nitride (u-g-C

Thurston, John H / Hunter, Necia M / Wayment, Lacey J / Cornell, Kenneth A

Journal of colloid and interface science

2017 Volume 505, Page(s) 910–918

Abstract: ... from urea-derived graphitic carbon nitride (u-g-C ...

Abstract	In this manuscript, we describe the fabrication of photoactive biocidal or sporicidal films from urea-derived graphitic carbon nitride (u-g-C
MeSH term(s)	Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Catalysis ; Escherichia coli/drug effects ; Escherichia coli/growth & development ; Graphite/chemistry ; Light ; Nitriles/chemistry ; Photochemical Processes ; Spores, Bacterial/drug effects ; Spores, Bacterial/growth & development ; Staphylococcus aureus/drug effects ; Staphylococcus aureus/growth & development ; Urea/chemistry
Chemical Substances	Anti-Bacterial Agents ; Nitriles ; cyanogen (534Q0F66RK) ; Graphite (7782-42-5) ; Urea (8W8T17847W)
Language	English
Publishing date	2017-06-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	241597-5
ISSN	1095-7103 ; 0021-9797
ISSN (online)	1095-7103
ISSN	0021-9797
DOI	10.1016/j.jcis.2017.06.089
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