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3,018 results on '"Morgan, Gareth J."'

7. Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens

Author

Maura, Francesco, Boyle, Eileen M., Coffey, David, Maclachlan, Kylee, Gagler, Dylan, Diamond, Benjamin, Ghamlouch, Hussein, Blaney, Patrick, Ziccheddu, Bachisio, Cirrincione, Anthony, Chojnacka, Monika, Wang, Yubao, Siegel, Ariel, Hoffman, James E., Kazandjian, Dickran, Hassoun, Hani, Guzman, Emily, Mailankody, Sham, Shah, Urvi A., Tan, Carlyn, Hultcrantz, Malin, Scordo, Michael, Shah, Gunjan L., Landau, Heather, Chung, David J., Giralt, Sergio, Zhang, Yanming, Arbini, Arnaldo, Gao, Qi, Roshal, Mikhail, Dogan, Ahmet, Lesokhin, Alexander M., Davies, Faith E., Usmani, Saad Z., Korde, Neha, Morgan, Gareth J., and Landgren, Ola

Published
2023
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11. The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma

Author

Cirrincione, Anthony M., Poos, Alexandra M., Ziccheddu, Bachisio, Kaddoura, Marcella, Bärtsch, Marc-Andrea, Maclachlan, Kylee, Chojnacka, Monika, Diamond, Benjamin, John, Lukas, Reichert, Philipp, Huhn, Stefanie, Blaney, Patrick, Gagler, Dylan, Rippe, Karsten, Zhang, Yanming, Dogan, Ahmet, Lesokhin, Alexander M., Davies, Faith, Goldschmidt, Hartmut, Fenk, Roland, Weisel, Katja C., Mai, Elias K., Korde, Neha, Morgan, Gareth J., Usmani, Saad, Landgren, Ola, Raab, Marc S., Weinhold, Niels, and Maura, Francesco

Published
2024
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15. BPAS Stenting

Author

Zablah, Jenny E., O’Callaghan, Barry, Morgan, Gareth J., and Mahadevan, Vaikom S., editor

Published
2023
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22. Maintenance lenalidomide in newly diagnosed transplant eligible and non-eligible myeloma patients; profiling second primary malignancies in 4358 patients treated in the Myeloma XI Trial

Author

Jones, John R., Cairns, David A., Menzies, Tom, Pawlyn, Charlotte, Davies, Faith E., Sigsworth, Rachel, Brioli, Annamaria, Jenner, Matthew W., Kaiser, Martin F., Olivier, Catherine, Reed, Molly, Drayson, Mark T., Owen, Roger G., Boyd, Kevin D., Cook, Gordon, Morgan, Gareth J., and Jackson, Graham H.

Published
2023
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24. A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry

Author

Du, Zhaohui, Weinhold, Niels, Song, Gregory Chi, Rand, Kristin A, Van Den Berg, David J, Hwang, Amie E, Sheng, Xin, Hom, Victor, Ailawadhi, Sikander, Nooka, Ajay K, Singhal, Seema, Pawlish, Karen, Peters, Edward S, Bock, Cathryn, Mohrbacher, Ann, Stram, Alexander, Berndt, Sonja I, Blot, William J, Casey, Graham, Stevens, Victoria L, Kittles, Rick, Goodman, Phyllis J, Diver, W Ryan, Hennis, Anselm, Nemesure, Barbara, Klein, Eric A, Rybicki, Benjamin A, Stanford, Janet L, Witte, John S, Signorello, Lisa, John, Esther M, Bernstein, Leslie, Stroup, Antoinette M, Stephens, Owen W, Zangari, Maurizio, Van Rhee, Frits, Olshan, Andrew, Zheng, Wei, Hu, Jennifer J, Ziegler, Regina, Nyante, Sarah J, Ingles, Sue Ann, Press, Michael F, Carpten, John David, Chanock, Stephen J, Mehta, Jayesh, Colditz, Graham A, Wolf, Jeffrey, Martin, Thomas G, Tomasson, Michael, Fiala, Mark A, Terebelo, Howard, Janakiraman, Nalini, Kolonel, Laurence, Anderson, Kenneth C, Le Marchand, Loic, Auclair, Daniel, Chiu, Brian C-H, Ziv, Elad, Stram, Daniel, Vij, Ravi, Bernal-Mizrachi, Leon, Morgan, Gareth J, Zonder, Jeffrey A, Huff, Carol Ann, Lonial, Sagar, Orlowski, Robert Z, Conti, David V, Haiman, Christopher A, and Cozen, Wendy

Subjects
Hematology, Rare Diseases, Genetics, Cancer, Clinical Research, Prevention, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Multiple Myeloma, Polymorphism, Single Nucleotide, Transcriptional Elongation Factors
Abstract

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

Published
2020

33. An updated AL-base reveals ranked enrichment of immunoglobulin light chain variable genes in AL amyloidosis.

Author

Morgan, Gareth J., Nau, Allison N., Wong, Sherry, Spencer, Brian H., Shen, Yun, Hua, Axin, Bullard, Matthew J., Sanchorawala, Vaishali, and Prokaeva, Tatiana

Abstract

AbstractBackgroundMethodsResultsConclusionsEach monoclonal antibody light chain associated with AL amyloidosis has a unique sequence. Defining how these sequences drive amyloid deposition could facilitate faster diagnosis and lead to new treatments.Light chain sequences are collected in the AL-Base repository. Monoclonal sequences from AL amyloidosis, multiple myeloma and the healthy polyclonal immune repertoire were compared to identify differences in precursor gene use, mutation frequency and physicochemical properties.AL-Base now contains 2,200 monoclonal light chain sequences from AL amyloidosis and other plasma cell dyscrasias. Sixteen germline precursor genes were enriched in AL amyloidosis, relative to multiple myeloma and the polyclonal repertoire. Two genes, IGKV1-16 and IGLV1-36, were infrequently observed but highly enriched in AL amyloidosis. The number of mutations varied widely between light chains. AL-associated κ light chains harboured significantly more mutations compared to multiple myeloma and polyclonal sequences, whereas AL-associated λ light chains had fewer mutations. Machine learning tools designed to predict amyloid propensity were less accurate for new sequences than their original training data.Rarely-observed light chain variable genes may carry a high risk of AL amyloidosis. New approaches are needed to define sequence-associated risk factors for AL amyloidosis. AL-Base is a foundational resource for such studies. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Perturbations of tryptophan catabolism via the kynurenine pathway are associated with stage 2 postoperative outcomes in single ventricle heart disease.

Author

Romanowicz, Jennifer, Niemiec, Sierra, Khailova, Ludmila, Lehmann, Tanner, Mancuso, Christopher A., Mitchell, Max B., Morgan, Gareth J., Twite, Mark, DiMaria, Michael V., Klawitter, Jelena, Davidson, Jesse A., and Frank, Benjamin S.

Subjects
PICOLINIC acid, HEART ventricles, CONGENITAL heart disease, HEART diseases, MASS spectrometry
Abstract

Preliminary evidence suggests perturbations of the kynurenine pathway (KP) of tryptophan metabolism in infants with single ventricle heart disease (SVHD). In 72 infants with SVHD undergoing stage 2 palliation (S2P) and 41 controls, we quantified serum KP metabolite concentrations via tandem mass spectroscopy pre‐S2P and post‐S2P at 2, 24, and 48 h and assessed metabolite relationships with post‐S2P outcomes (length of stay, hypoxemia burden, and intubation duration). Pre‐S2P, SVHD infants had lower tryptophan and serotonin levels and higher kynurenic acid, 3‐hydroxykynurenine, and picolinic acid levels than controls. Post‐S2P, metabolites peaked at 2 h, with return to baseline by 48 h for all except kynurenic acid, which remained elevated. Metabolite concentrations pre‐S2P were poorly associated with outcomes. A lower serotonin peak 2 h post‐S2P was associated with longer length of stay and intubation duration. Multiple metabolites at 24 and 48 h correlated with outcomes; notably, elevated kynurenic acid was associated with worse results for all three outcomes. Our results confirm that interstage SVHD infants have altered KP activity compared to controls. Further, the link between outcomes and KP metabolites post‐S2P—but not at baseline—demonstrates that acute, perioperative changes in tryptophan catabolism may be more important to tolerating S2P physiology than chronic interstage changes. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Predicting Structural Consequences of Antibody Light Chain N-Glycosylation in AL Amyloidosis.

Author

Morgan, Gareth J., Yung, Zach, Spencer, Brian H., Sanchorawala, Vaishali, and Prokaeva, Tatiana

Abstract

Background/Objectives: Antibody light chains form amyloid fibrils that lead to progressive tissue damage in amyloid light chain (AL) amyloidosis. The properties of each patient's unique light chain appear to determine its propensity to form amyloid. One factor is N-glycosylation, which is more frequent in amyloid-associated light chains than in light chains from the normal immune repertoire. However, the mechanisms underlying this association are unknown. Here, we investigate the frequency and position within the light chain sequence of the N-glycosylation sequence motif, or sequon. Methods: Monoclonal light chains from AL amyloidosis and multiple myeloma were identified from the AL-Base repository. Polyclonal light chains were obtained from the Observed Antibody Space resource. We compared the fraction of light chains from each group harboring an N-glycosylation sequon, and the positions of these sequons within the sequences. Results: Sequons are enriched among AL-associated light chains derived from a subset of precursor germline genes. Sequons are observed at multiple positions, which differ between the two types of light chains, κ and λ, but are similar between light chains from AL amyloidosis and multiple myeloma. Positions of sequons map to residues with surface-exposed sidechains that are compatible with the folded structures of light chains. Within the known structures of λ AL amyloid fibrils, many residues where sequons are observed are buried, inconsistent with N-glycosylation. Conclusions: There is no clear structural rationale for why N-glycosylation of κ light chains is associated with AL amyloidosis. A better understanding of the roles of N-glycosylation in AL amyloidosis is required before it can be used as a marker for disease risk. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Plasma cells expression from smouldering myeloma to myeloma reveals the importance of the PRC2 complex, cell cycle progression, and the divergent evolutionary pathways within the different molecular subgroups

Author

Boyle, Eileen M., Rosenthal, Adam, Ghamlouch, Hussein, Wang, Yan, Farmer, Phillip, Rutherford, Michael, Ashby, Cody, Bauer, Michael, Johnson, Sarah K., Wardell, Christopher P., Wang, Yubao, Hoering, Antje, Schinke, Carolina, Thanendrarajan, Sharmilan, Zangari, Maurizio, Barlogie, Bart, Dhodapkar, Madhav V., Davies, Faith E., Morgan, Gareth J., van Rhee, Frits, and Walker, Brian A.

Published
2022
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42. Improving prognostic assignment in older adults with multiple myeloma using acquired genetic features, clonal hemopoiesis and telomere length

Author

Boyle, Eileen M., Williams, Louis, Blaney, Patrick, Ashby, Cody, Bauer, Michael, Walker, Brian A., Ghamlouch, Hussein, Choi, Jinyoung, Perrial, Emeline, Wang, Yubao, Caro, Jessica, Stoeckle, James H., Arbini, Arnaldo, Kaminetzky, David, Braunstein, Marc, Bruno, Benedetto, Razzo, Beatrice, Diamond, Benjamin, Maclachlan, Kylee, Maura, Francesco, Landgren, Ola, Litke, Rachel, Fegan, Christopher D., Keats, Johnathan, Auclair, Daniel, Davies, Faith E., and Morgan, Gareth J.

Published
2022
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44. Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes

Author

Bustoros, Mark, Anand, Shankara, Sklavenitis-Pistofidis, Romanos, Redd, Robert, Boyle, Eileen M., Zhitomirsky, Benny, Dunford, Andrew J., Tai, Yu-Tzu, Chavda, Selina J., Boehner, Cody, Neuse, Carl Jannes, Rahmat, Mahshid, Dutta, Ankit, Casneuf, Tineke, Verona, Raluca, Kastritis, Efstathis, Trippa, Lorenzo, Stewart, Chip, Walker, Brian A., Davies, Faith E., Dimopoulos, Meletios-Athanasios, Bergsagel, P. Leif, Yong, Kwee, Morgan, Gareth J., Aguet, François, Getz, Gad, and Ghobrial, Irene M.

Published
2022
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49. Definitions of adverse events associated with extracorporeal membrane oxygenation in children: results of an international Delphi process from the ECMO-CENTRAL ARC

Author

Alexander, Peta M A, Di Nardo, Matteo, Combes, Alain, Vogel, Adam M, Antonini, Marta Velia, Barrett, Nicholas, Benedetti, Giulia M, Bettencourt, Amanda, Brodie, Daniel, Gómez-Gutiérrez, René, Gorga, Stephen M, Hodgson, Carol, Kapoor, Poonam Malhotra, Le, Jennifer, MacLaren, Graeme, O’Neil, Erika R, Ostermann, Marlies, Paden, Matthew L, Patel, Neil, Rojas-Peña, Alvaro, Said, Ahmed S, Sperotto, Francesca, Willems, Ariane, Vercaemst, Leen, Yoganathan, Ajit P, Lorts, Angela, del Nido, Pedro J, Barbaro, Ryan P, Abecasis, Francisco, Al Foudri, Huda, Anders, Marc M., Angus, Derek C., Annich, Gail M., Arachchillage, Deepa J., Akcan-Arikan, Ayse, Armstrong, Aimee K., Balcells, Joan, Barrett, Meredith, Bartlett, Robert H., Belda-Hofheinz, Sylvia, Bembea, Melania M., Best, Derek J., Bonadonna, Desiree, Boonstra, Philip S., Brogan, Thomas V, Brown, Katherine L, Butragueño-Laiseca, Laura, Butt, Warwick W., Camporota, Luigi, Cardenas, Barbara, Cascarano, Maria T., Caspi, Joseph, Chen, Eric, Chiletti, Roberto, Colombo, Giovanna G., Conte, Marisa L., Crowe, Liz, Cvetkovic, Mirjana, Dalton, Heidi J., Daverio, Marco, Davidson, Mark G., Davis, Carl, DiGeronimo, Robert J., Egbunine, Ariel, Ellis, W. Cory, Fan, Eddy, Foster, Claire C, Fraser, John F., Friedman, Matthew L., Furlong-Dillard, Jamie, Fynn-Thompson, Francis, Garcia, Alejandro V., Geppert, Jeffery, Gillette, Nicole, Grazioli, Lorenzo, Greene, Christina L, Guerguerian, Anne-Marie, Guilliams, Kristin P., Haji Fortis, Jumana Y., Hao, Jianming, Heinsar, Silver, Hejduk, Mark W., Himebauch, Adam S., Horvat, Christopher M., Hoskote, Aparna, Hou, Xiaotong, Hyslop, Robert W., Ibrahim, Nicole, Ito, Takuya, Karagiannidis, Christian, Karam, Oliver, Kaushik, Shubhi, Kilbaugh, Todd J., Kim-Campbell, Nahmah, Kirsch, Roxanne E, Kormos, Robert L., Kornberger, Angela, Krucoff, Mitchell W., Lakshminrusimha, Satyan, LaRovere, Kerri L, Leger, Pierre-Louis, Levy, Philip T., Lorusso, Roberto, Lyster, Haifa, Malone, Matthew P., McMullan, D. Michael, Mečířová, Soña, Mehran, Roxana, Merz, Scott I., Mochizuki, Shuichi, Moler, Frank W., Molla, Kalkidan, Monagle, Paul, Morgan, Gareth J., Morgan, Catherine, Morice, Marie-Claude, Muszynski, Jennifer A., Najaf, Tasnim A., Nellis, Marianne E., Newburger, Jane W., O'Rourke, P. Pearl, Ostadal, Petr, Ozment, Caroline P., Pagani, Francis D., Peek, Giles J., Polito, Angelo, Priest, John R., Raman, Lakshmi, Rintoul, Natalie E., Roy, Nathalie, Rubin, Juli, Rumford, Martha, Rycus, Peter, Ryerson, Lindsay M., Sakamoto, Wakako, Segura-Matute, Susana, Shekar, Kiran, Spinella, Philip C., Spitzer, Ernest, Starr, Joanne P., Stead, Christine, Steffen, Katherine, Steiner, Marie E., Tan, Lucy, Tasker, Robert C., Taylor, J. Michael, Thiagarajan, Ravi R., Tonna, Joseph E., Ubertini, Gina M., van Leeuwen, Grace, Vang, Eric, Ventetuolo, Corey E., Venugopal, Prem S., Weinberg, Allison, Westrope, Claire, Wu, Changfu, Wylie, Gillian, Zeymer, Uwe, Zivick, Elizabeth E., and Zochios, Vasileios

Abstract

Extracorporeal membrane oxygenation (ECMO) is a high-risk and low-volume life support with increasing clinical study. However, heterogenous outcome definitions impede data assimilation into evidence to guide practice. The Academic Research Consortium (ARC), an international collaborative forum committed to facilitating the creation of stakeholder-driven consensus nomenclature and outcomes for clinical trials of medical devices, supported the ECMO Core Elements Needed for Trials Regulation And quality of Life (ECMO-CENTRAL) ARC. The ECMO-CENTRAL ARC was assembled to develop definitions of paediatric ECMO adverse events for use in clinical trials and regulatory device evaluation. An initial candidate list of ECMO adverse events derived from the mechanical circulatory support ARC was supplemented with a review of ECMO-relevant adverse event definitions collated from literature published between Jan 1, 1988, and Feb 20, 2023. Distinct teams of international topic experts drafted separate adverse event definitions that were harmonised to existing literature when appropriate. Draft definitions were revised for paediatric ECMO relevance with input from patients, families, and an international expert panel of trialists, clinicians, statisticians, biomedical engineers, device developers, and regulatory agencies. ECMO-CENTRAL ARC was revised and disseminated across research societies and professional organisations. Up to three rounds of internet-based anonymous surveys were planned as a modified Delphi process. The expert panel defined 13 adverse event definitions: neurological, bleeding, device malfunction, acute kidney injury, haemolysis, infection, vascular access-associated injury, non-CNS thrombosis, hepatic dysfunction, right heart failure, left ventricular overload, lactic acidaemia, and hypoxaemia. Definitional structure varied. Among 165 expert panel members, 114 were eligible to vote and 111 voted. Consensus was achieved for all proposed definitions. Agreement ranged from 82% to 95%. ECMO-CENTRAL ARC paired rigorous development with methodical stakeholder involvement and dissemination to define paediatric ECMO adverse events. These definitions will facilitate new research and the assimilation of data across clinical trials and ECMO device evaluation in children.

Published
2024
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50. Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial

Author

Croft, James, Ellis, Sidra, Sherborne, Amy L., Sharp, Kim, Price, Amy, Jenner, Matthew W., Drayson, Mark T., Owen, Roger G., Chown, Sally, Lindsay, Jindriska, Karunanithi, Kamaraj, Hunter, Hannah, Gregory, Walter M., Davies, Faith E., Morgan, Gareth J., Cook, Gordon, Atanesyan, Lilit, Savola, Suvi, Cairns, David A., Jackson, Graham, Houlston, Richard S., and Kaiser, Martin F.

Published
2021
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