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151. Feasibility of indocyanine green‐guided localization of pulmonary nodules in children with solid tumors

Author

Abdelhafeez, Abdelhafeez H., primary, Mothi, Suraj Sarvode, additional, Pio, Luca, additional, Mori, Motomi, additional, Santiago, Teresa C., additional, McCarville, M. Beth, additional, Kaste, Sue C., additional, Pappo, Alberto S., additional, Talbot, Lindsay J., additional, Murphy, Andrew J., additional, and Davidoff, Andrew M., additional

Published
2023
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156. The pathophysiology of bilateral and multifocal Wilms tumors: What we can learn from the study of predisposition syndromes

Author

Child Health, Cancer, Genetica Klinische Genetica, Welter, Nils, Brzezinski, Jack, Treece, Amy, Chintagumpala, Murali, Young, Matthew D, Perotti, Daniela, Kieran, Kathleen, Jongmans, Marjolijn C J, Murphy, Andrew J, Child Health, Cancer, Genetica Klinische Genetica, Welter, Nils, Brzezinski, Jack, Treece, Amy, Chintagumpala, Murali, Young, Matthew D, Perotti, Daniela, Kieran, Kathleen, Jongmans, Marjolijn C J, and Murphy, Andrew J

Published
2023

160. Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor

Author

Murphy, Andrew J., Chen, Xiang, Pinto, Emilia M., Williams, Justin S., Clay, Michael R., Pounds, Stanley B., Cao, Xueyuan, Shi, Lei, Lin, Tong, Neale, Geoffrey, Morton, Christopher L., Woolard, Mary A., Mulder, Heather L., Gil, Hyea Jin, Rehg, Jerold E., Billups, Catherine A., Harlow, Matthew L., Dome, Jeffrey S., Houghton, Peter J., Easton, John, Zhang, Jinghui, George, Rani E., Zambetti, Gerard P., and Davidoff, Andrew M.

Published
2019
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161. Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease.

Author

Kott, Katharine A, Chan, Adam S, Vernon, Stephen T, Hansen, Thomas, Kim, Taiyun, de Dreu, Macha, Gunasegaran, Bavani, Murphy, Andrew J, Patrick, Ellis, Psaltis, Peter J, Grieve, Stuart M, Yang, Jean Y, Fazekas de St Groth, Barbara, McGuire, Helen M, and Figtree, Gemma A

Subjects
CORONARY artery disease, CYTOMETRY, DISEASE risk factors, REGULATORY T cells, B cells
Abstract

Objective: The importance of inflammation in atherosclerosis is well accepted, but the role of the adaptive immune system is not yet fully understood. To further explore this, we assessed the circulating immune cell profile of patients with coronary artery disease (CAD) to identify discriminatory features by mass cytometry. Methods: Mass cytometry was performed on patient samples from the BioHEART‐CT study, gated to detect 82 distinct cell subsets. CT coronary angiograms were analysed to categorise patients as having CAD (CAD+) or having normal coronary arteries (CAD−). Results: The discovery cohort included 117 patients (mean age 61 ± 12 years, 49% female); 79 patients (68%) were CAD+. Mass cytometry identified changes in 15 T‐cell subsets, with higher numbers of proliferating, highly differentiated and cytotoxic cells and decreases in naïve T cells. Five T‐regulatory subsets were related to an age and gender‐independent increase in the odds of CAD incidence when expressing CCR2 (OR 1.12), CCR4 (OR 1.08), CD38 and CD45RO (OR 1.13), HLA‐DR (OR 1.06) and Ki67 (OR 1.22). Markers of proliferation and differentiation were also increased within B cells, while plasmacytoid dendritic cells were decreased. This combination of changes was assessed using SVM models in discovery and validation cohorts (area under the curve = 0.74 for both), confirming the robust nature of the immune signature detected. Conclusion: We identified differences within immune subpopulations of CAD+ patients which are indicative of a systemic immune response to coronary atherosclerosis. This immune signature needs further study via incorporation into risk scoring tools for the precision diagnosis of CAD. [ABSTRACT FROM AUTHOR]

Published
2023
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162. Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes.

Author

Oostveen, Reindert F., Kaiser, Yannick, Ståhle, Mia R., Nurmohamed, Nick S., Tzolos, Evangelos, Dweck, Marc R., Kroon, Jeffrey, Murphy, Andrew J., Dey, Damini, Slomka, Piotr J., Verberne, Hein J., Stroes, Erik S. G., and Hanssen, Nordin M. J.

Abstract

Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. Methods: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). Results: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was −31% (95% CI −50, −12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of −15% (95% CI −27, −4) and −17% (95% CI −32, −2), respectively. Conclusions/interpretation: 68Ga-DOTATATE uptake across the cardio–haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT05730634 [ABSTRACT FROM AUTHOR]

Published
2023
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163. Neutrophil-Derived S100A8/A9 Amplify Granulopoiesis After Myocardial Infarction

Author

Sreejit, Gopalkrishna, Abdel-Latif, Ahmed, Athmanathan, Baskaran, Annabathula, Rahul, Dhyani, Ashish, Noothi, Sunil K., Quaife-Ryan, Gregory A., Al-Sharea, Annas, Pernes, Gerard, Dragoljevic, Dragana, Lal, Hind, Schroder, Kate, Hanaoka, Beatriz Y., Raman, Chander, Grant, Maria B., Hudson, James E., Smyth, Susan S., Porrello, Enzo R., Murphy, Andrew J., and Nagareddy, Prabhakara R.

Published
2020
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167. The Genetic and Epigenetic Features of Bilateral Wilms Tumor Predisposition: A Report from the Children's Oncology Group AREN18B5-Q Study

Author

Murphy, Andrew J., primary, Cheng, Changde, additional, Williams, Justin, additional, Shaw, Timothy I., additional, Pinto, Emilia M., additional, Dieseldorff-Jones, Karissa, additional, Brzezinski, Jack, additional, Renfro, Lindsay A., additional, Tornwall, Brett, additional, Huff, Vicki, additional, Hong, Andrew L., additional, Mullen, Elizabeth A., additional, Crompton, Brian, additional, Dome, Jeffrey S., additional, Fernandez, Conrad V., additional, Geller, James I., additional, Ehrlich, Peter F., additional, Mulder, Heather, additional, Oak, Ninad, additional, Maciezsek, Jamie, additional, Jablonowski, Carolyn, additional, Fleming, Andrew M., additional, Pichavaram, Prahalathan, additional, Morton, Christopher L., additional, Easton, John, additional, Nichols, Kim E., additional, Clay, Michael R., additional, Santiago, Teresa, additional, Zhang, Jinghui, additional, Yang, Jun, additional, Zambetti, Gerard P., additional, Wang, Zhaoming, additional, Davidoff, Andrew M., additional, and Chen, Xiang, additional

Published
2023
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168. Divergent roles for caspase-8 and MLKL in high-fat diet induced obesity and NAFLD in mice

Author

Tye, Hazel, primary, Conos, Stephanie A, additional, Djajawi, Tirta M, additional, Abdoulkader, Nasteho, additional, Kong, Isabella Y, additional, Kaummon, Helene L, additional, Narayana, Vinod K, additional, Speir, Mary, additional, Gottschalk, Timothy A, additional, Emery, Jack, additional, Simpson, Daniel S, additional, Hall, Cathrine, additional, Vince, Angelina J, additional, Russo, Sophia, additional, Crawley, Rhiannan, additional, Rashidi, Maryam, additional, Hildebrand, Joanne, additional, Murphy, James M, additional, Whitehead, Lachlan, additional, De Souza, David P., additional, Masters, Seth L, additional, Hawkins, Edwin D, additional, Murphy, Andrew J, additional, Vince, James, additional, and Lawlor, Kate, additional

Published
2023
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169. Structural insights into the assembly of gp130 family cytokine signaling complexes

Author

Zhou, Yi, primary, Stevis, Panayiotis E., additional, Cao, Jing, additional, Saotome, Kei, additional, Wu, Jiaxi, additional, Glatman Zaretsky, Arielle, additional, Haxhinasto, Sokol, additional, Yancopoulos, George D., additional, Murphy, Andrew J., additional, Sleeman, Mark W., additional, Olson, William C., additional, and Franklin, Matthew C., additional

Published
2023
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170. Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Author

Barrachina, Maria N, primary, Pernes, Gerard, additional, Becker, Isabelle C, additional, Allaeys, Isabelle, additional, Hirsch, Thomas I., additional, Groeneveld, Dafna J, additional, Khan, Abdullah O., additional, Freire, Daniela, additional, Guo, Karen, additional, Carminita, Estelle, additional, Morgan, Pooranee K, additional, Collins, Thomas J, additional, Mellett, Natalie A, additional, Wei, Zimu, additional, Almazni, Ibrahim, additional, Italiano, Joseph E., additional, Luyendyk, James, additional, Meikle, Peter J, additional, Puder, Mark, additional, Morgan, Neil V., additional, Boilard, Eric, additional, Murphy, Andrew J, additional, and Machlus, Kellie R, additional

Published
2023
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171. An immune cell lipid atlas reveals the basis of susceptibility to ferroptosis

Author

Pernes, Gerard, primary, Morgan, Pooranee K, additional, Huynh, Kevin, additional, Giles, Corey, additional, Paul, Sudip, additional, Smith, Adam Alexander T, additional, Mellett, Natalie A, additional, Veiga, Camilla Bertuzzo, additional, Collins, Thomas JC, additional, De Silva, T Michael, additional, Lee, Man KS, additional, Meikle, Peter J, additional, Lancaster, Graeme I, additional, and Murphy, Andrew J, additional

Published
2023
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172. IL-4 and IL-13, not eosinophils, drive type 2 airway inflammation, remodeling and lung function decline

Author

Scott, George, primary, Asrat, Seblewongel, additional, Allinne, Jeanne, additional, Keat Lim, Wei, additional, Nagashima, Kirsten, additional, Birchard, Dylan, additional, Srivatsan, Subhashini, additional, Ajithdoss, Dharani K., additional, Oyejide, Adelekan, additional, Ben, Li-Hong, additional, Walls, Johnathon, additional, Le Floc'h, Audrey, additional, Yancopoulos, George D., additional, Murphy, Andrew J., additional, Sleeman, Matthew A., additional, and Orengo, Jamie M., additional

Published
2023
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173. Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice

Author

Hanssen, Nordin M.J., primary, Tikellis, Chris, additional, Pickering, Raelene J., additional, Dragoljevic, Dragana, additional, Lee, Man Kit Sam, additional, Block, Tomasz, additional, Scheijen, Jean LJM, additional, Wouters, Kristiaan, additional, Miyata, Toshio, additional, Cooper, Mark E., additional, Murphy, Andrew J., additional, Thomas, Merlin C., additional, and Schalkwijk, Casper G., additional

Published
2023
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174. Late Health Outcomes Among Survivors of Wilms Tumor Diagnosed Over Three Decades: A Report From the Childhood Cancer Survivor Study

Author

Weil, Brent R., primary, Murphy, Andrew J., additional, Liu, Qi, additional, Howell, Rebecca M., additional, Smith, Susan A., additional, Weldon, Christopher B., additional, Mullen, Elizabeth A., additional, Madenci, Arin L., additional, Leisenring, Wendy M., additional, Neglia, Joseph P., additional, Turcotte, Lucie M., additional, Oeffinger, Kevin C., additional, Termuhlen, Amanda M., additional, Mostoufi-Moab, Sogol, additional, Levine, Jennifer M., additional, Krull, Kevin R., additional, Yasui, Yutaka, additional, Robison, Leslie L., additional, Armstrong, Gregory T., additional, Chow, Eric J., additional, and Armenian, Saro H., additional

Published
2023
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176. Blocking common γ chain cytokine signaling ameliorates T cell–mediated pathogenesis in disease models

Author

Le Floc’h, Audrey, primary, Nagashima, Kirsten, additional, Birchard, Dylan, additional, Scott, George, additional, Ben, Li-Hong, additional, Ajithdoss, Dharani, additional, Gayvert, Kaitlyn, additional, Romero Hernandez, Annabel, additional, Herbin, Olivier, additional, Tay, Amanda, additional, Farrales, Pamela, additional, Korgaonkar, Chandrashekhar K., additional, Pan, Hao, additional, Shah, Sweta, additional, Kamat, Vishal, additional, Chatterjee, Ishita, additional, Popke, Jon, additional, Oyejide, Adelekan, additional, Lim, Wei Keat, additional, Kim, Jee H., additional, Huang, Tammy, additional, Franklin, Matthew, additional, Olson, William, additional, Norton, Thomas, additional, Perlee, Lorah, additional, Yancopoulos, George D., additional, Murphy, Andrew J., additional, Sleeman, Matthew A., additional, and Orengo, Jamie M., additional

Published
2023
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177. Administration of an LXR agonist promotes atherosclerotic lesion remodelling in murine inflammatory arthritis

Author

Dragoljevic, Dragana, primary, Lee, Man Kit Sam, additional, Pernes, Gerard, additional, Morgan, Pooranee K, additional, Louis, Cynthia, additional, Shihata, Waled, additional, Huynh, Kevin, additional, Kochetkova, Arina A, additional, Bell, Patrick W, additional, Mellett, Natalie A, additional, Meikle, Peter J, additional, Lancaster, Graeme I, additional, Kraakman, Michael J, additional, Nagareddy, Prabhakara R, additional, Hanaoka, Beatriz Y, additional, Wicks, Ian P, additional, and Murphy, Andrew J, additional

Published
2023
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180. IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome

Author

Murphy, Andrew J., Kraakman, Michael J., Kammoun, Helene L., Dragoljevic, Dragana, Lee, Man K.S., Lawlor, Kate E., Wentworth, John M., Vasanthakumar, Ajithkumar, Gerlic, Motti, Whitehead, Lachlan W., DiRago, Ladina, Cengia, Louise, Lane, Rachael M., Metcalf, Donald, Vince, James E., Harrison, Leonard C., Kallies, Axel, Kile, Benjamin T., Croker, Ben A., Febbraio, Mark A., and Masters, Seth L.

Published
2016
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182. A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells

Author

Cruz, Jonathan W., Damko, Ermelinda, Modi, Bhavika, Tu, Naxin, Meagher, Karoline, Voronina, Vera, Gartner, Hans, Ehrlich, George, Rafique, Ashique, Babb, Robert, Aneja, Priya, Potocky, Terra B., D’ Orvilliers, Amanda, Coppi, Alida, E, Sook Yen, Qiu, Haibo, Williams, Courtney M., Bennett, Brandy L., Chen, Gang, Macdonald, Lynn, Olson, William, Lin, John C., Stahl, Neil, Murphy, Andrew J., Kyratsous, Christos A., and Prasad, Brinda C.

Published
2019
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183. A cellular and molecular spatial atlas of dystrophic muscle.

Author

Steca, Michael J., Qi Sua, Adler, Christina, Zhang, Lance, Golann, David R., Khan, Naveen P., Panagis, Lampros, Armando Villalta, S., Min Ni, Yi Wei, Walls, Johnathon R., Murphy, Andrew J., Yancopoulos, George D., Atwal, Gurinder S., Kleiner, Sandra, Halasz, Gabor, and Sleeman, Mark W.

Subjects
DUCHENNE muscular dystrophy, SKELETAL muscle, GENE expression, DNA probes, CELL populations
Abstract

Asynchronous skeletal muscle degeneration/regeneration is a hallmark feature of Duchenne muscular dystrophy (DMD); however, traditional -omics technologies that lack spatial context make it difficult to study the biological mechanisms of how asynchronous regeneration contributes to disease progression. Here, using the severely dystrophic D2-mdx mouse model, we generated a high-resolution cellular and molecular spatial atlas of dystrophic muscle by integrating spatial transcriptomics and single-cell RNAseq datasets. Unbiased clustering revealed nonuniform distribution of unique cell populations throughout D2-mdx muscle that were associated with multiple regenerative timepoints, demonstrating that this model faithfully recapitulates the asynchronous regeneration observed in human DMD muscle. By probing spatiotemporal gene expression signatures, we found that propagation of inflammatory and fibrotic signals from locally damaged areas contributes to widespread pathology and that querying expression signatures within discrete microenvironments can identify targetable pathways for DMD therapy. Overall, this spatial atlas of dystrophic muscle provides a valuable resource for studying DMD disease biology and therapeutic target discovery. [ABSTRACT FROM AUTHOR]

Published
2023
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184. Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance

Author

Kraakman, Michael J., Kammoun, Helene L., Allen, Tamara L., Deswaerte, Virginie, Henstridge, Darren C., Estevez, Emma, Matthews, Vance B., Neill, Bronwyn, White, David A., Murphy, Andrew J., Peijs, Lone, Yang, Christine, Risis, Steve, Bruce, Clinton R., Du, Xiao-Jun, Bobik, Alex, Lee-Young, Robert S., Kingwell, Bronwyn A., Vasanthakumar, Ajithkumar, Shi, Wei, Kallies, Axel, Lancaster, Graeme I., Rose-John, Stefan, and Febbraio, Mark A.

Published
2015
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185. Cancer cell-derived type I interferons instruct tumor monocyte polarization

Author

Kwart, Dylan, primary, He, Jing, additional, Srivatsan, Subhashini, additional, Lett, Clarissa, additional, Golubov, Jacquelynn, additional, Oswald, Erin M., additional, Poon, Patrick, additional, Ye, Xuan, additional, Waite, Janelle, additional, Zaretsky, Arielle Glatman, additional, Haxhinasto, Sokol, additional, Au-Yeung, Elsa, additional, Gupta, Namita T., additional, Chiu, Joyce, additional, Adler, Christina, additional, Cherravuru, Samvitha, additional, Malahias, Evangelia, additional, Negron, Nicole, additional, Lanza, Kathryn, additional, Coppola, Angel, additional, Ni, Min, additional, Song, Hang, additional, Wei, Yi, additional, Atwal, Gurinder S., additional, Macdonald, Lynn, additional, Oristian, Nicole Stokes, additional, Poueymirou, William, additional, Jankovic, Vladimir, additional, Fury, Matthew, additional, Lowy, Israel, additional, Murphy, Andrew J., additional, Sleeman, Matthew A., additional, Wang, Bei, additional, and Skokos, Dimitris, additional

Published
2022
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186. Germline Missense Variants in SH2B3 Underpin Platelet Count Variation and Inherited MPN

Author

Butler, Liesl, primary, Lee, Christine, additional, Magor, Graham William, additional, Morris, Rhiannon, additional, Tallack, Michael, additional, Lam, Charlene, additional, Ivey, Adam, additional, Lin, Jane, additional, Deng, Zihao, additional, Grigg, Andrew, additional, Mason, Jane, additional, Perchard, Malaika, additional, Weston, Helen, additional, Cummings, Nik, additional, Brooks, Andrew, additional, Babon, Jeffrey J, additional, Murphy, Andrew J, additional, Salmon, Jessica M, additional, and Perkins, Andrew Charles, additional

Published
2022
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187. The Effect of Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Aspirin on Clinical Outcomes in the Healthy Elderly: A Sub-Study of the Aspirin in Reducing Events in the Elderly (ASPREE) Randomized Controlled Trial

Author

McQuilten, Zoe, primary, Wong, Nicholas C., additional, Leichter, Anna, additional, Thao, Le T.P., additional, Phung, James, additional, Murphy, Andrew J, additional, Riaz, Moeen, additional, Sebra, Robert, additional, Bick, Alexander G., additional, McNeil, John J., additional, Wolfe, Rory, additional, Woods, Robyn L., additional, Lacaze, Paul, additional, Wood, Erica M., additional, and Curtis, David J., additional

Published
2022
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188. Evaluation of Common Gamma Chain Cytokine Signaling Blockade with REGN7257, an Interleukin 2 Receptor Gamma (IL2RG) Monoclonal Antibody, on Immune Cell Populations in Monkey and Human

Author

Le Floch-Ramondou, Audrey, primary, Nagashima, Kirsten, additional, Gayvert, Kaitlyn, additional, Pan, Hao, additional, Korgaonkar, Chandrashekhar, additional, Shakil, Hassan, additional, Ullman, Erica, additional, Norton, Thomas, additional, Perlee, Lorah, additional, Murphy, Andrew J., additional, Sleeman, Matthew, additional, and Orengo, Jamie, additional

Published
2022
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189. The Growth Kinetics of Clonal Hematopoiesis Inform Risk of Blood Cancer Progression

Author

Curtis, David J., primary, Wong, Nicholas C., additional, Leichter, Anna, additional, Thao, Le T.P., additional, Phung, James, additional, Murphy, Andrew J, additional, Riaz, Moeen, additional, Sebra, Robert, additional, Bick, Alexander G., additional, McNeil, John J., additional, Wolfe, Rory, additional, Woods, Robyn L., additional, Lacaze, Paul, additional, Wood, Erica M., additional, and McQuilten, Zoe, additional

Published
2022
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190. Blockade of Common Gamma Chain Cytokine Signaling with REGN7257, an Interleukin 2 Receptor Gamma (IL2RG) Monoclonal Antibody, Protected Mice from Inflammatory and Autoimmune Diseases

Author

Le Floch-Ramondou, Audrey, primary, Nagashima, Kirsten, additional, Farrales, Pamela, additional, Tay, Amanda, additional, Herbin, Olivier, additional, Ajithdoss, Dharani, additional, Norton, Thomas, additional, Perlee, Lorah, additional, Murphy, Andrew J., additional, Sleeman, Matthew, additional, and Orengo, Jamie, additional

Published
2022
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191. CD22-targeted CD28 bispecific antibody enhances antitumor efficacy of odronextamab in refractory diffuse large B cell lymphoma models

Author

Wei, Joyce, primary, Montalvo-Ortiz, Welby, additional, Yu, Lola, additional, Krasco, Amanda, additional, Olson, Kara, additional, Rizvi, Sahar, additional, Fiaschi, Nathalie, additional, Coetzee, Sandra, additional, Wang, Fang, additional, Ullman, Erica, additional, Ahmed, Hassan Shakil, additional, Herlihy, Evan, additional, Lee, Ken, additional, Havel, Lauren, additional, Potocky, Terra, additional, Ebstein, Sarah, additional, Frleta, Davor, additional, Khatri, Aditi, additional, Godin, Stephen, additional, Hamon, Sara, additional, Brouwer-Visser, Jurriaan, additional, Gorenc, Travis, additional, MacDonald, Doug, additional, Hermann, Aynur, additional, Chaudhry, Aafia, additional, Sirulnik, Andres, additional, Olson, William, additional, Lin, John, additional, Thurston, Gavin, additional, Lowy, Israel, additional, Murphy, Andrew J., additional, Smith, Eric, additional, Jankovic, Vladimir, additional, Sleeman, Matthew A., additional, and Skokos, Dimitris, additional

Published
2022
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193. Extracellular vesicles carrying HIV-1 Nef induce long-term hyperreactivity of myeloid cells

Author

Dubrovsky, Larisa, primary, Brichacek, Beda, additional, Prashant, N.M., additional, Pushkarsky, Tatiana, additional, Mukhamedova, Nigora, additional, Fleetwood, Andrew J., additional, Xu, Yangsong, additional, Dragoljevic, Dragana, additional, Fitzgerald, Michael, additional, Horvath, Anelia, additional, Murphy, Andrew J., additional, Sviridov, Dmitri, additional, and Bukrinsky, Michael I., additional

Published
2022
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196. IgG Subclass-Dependent Pulmonary Antigen Retention during Acute IgG-Dependent Systemic Anaphylaxis in Mice

Author

Todorova, Biliana, primary, Godon, Ophélie, additional, Conde, Eva, additional, Gillis, Caitlin M., additional, Iannascoli, Bruno, additional, Richard-Le Goff, Odile, additional, Fiole, Daniel, additional, Roumenina, Lubka T., additional, Leusen, Jeanette H. W., additional, Murphy, Andrew J., additional, Macdonald, Lynn E., additional, Reber, Laurent L., additional, Jönsson, Friederike, additional, and Bruhns, Pierre, additional

Published
2022
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197. Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes

Author

Kraakman, Michael J., Lee, Man K.S., Al-Sharea, Annas, Dragoljevic, Dragana, Barrett, Tessa J., Montenont, Emilie, Basu, Debapriya, Heywood, Sarah, Kammoun, Helene L., Flynn, Michelle, Whillas, Alexandra, Hanssen, Nordin M.J., Febbraio, Mark A., Westein, Erik, Fisher, Edward A., Chin -Dusting, Jaye, Cooper, Mark E., Berger, Jeffrey S., Goldberg, Ira J., Nagareddy, Prabhakara R., and Murphy, Andrew J.

Subjects
Thrombocytosis -- Development and progression, Diabetes mellitus -- Complications and side effects, Calcium binding proteins -- Health aspects, Health care industry
Abstract

Platelets play a critical role In atherogenesis and thrombosis-mediated myocardial Ischemia, processes that are accelerated In diabetes. Whether hyperglycemia promotes platelet production and whether enhanced platelet production contributes to enhanced atherothrombosis remains unknown. Here we found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL-6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis. IL-6 acts on hepatocytes to enhance the production of thrombopoietin, which in turn interacts with its cognate receptor c-MPL on megakaryocytes and bone marrow progenitor cells to promote their expansion and proliferation, resulting in reticulated thrombocytosis. Lowering blood glucose using a sodium -glucose cotransporter 2 inhibitor (dapagliflozin), depleting neutrophils or Kupffer cells, or inhibiting S100A8/A9 binding to RAGE (using paquinimod), all reduced diabetes-induced thrombocytosis. Inhibiting S100A8/A9 also decreased atherogenesis in diabetic mice. Finally, we found that patients with type 2 diabetes have reticulated thrombocytosis that correlates with glycated hemoglobin as well as increased plasma S100A8/A9 levels. These studies provide insights into the mechanisms that regulate platelet production and may aid in the development of strategies to improve on current antiplatelet therapies and to reduce cardiovascular disease risk in diabetes., Introduction Diabetes is a major risk factor for cardiovascular disease (CVD), which remains the leading cause of mortality worldwide (1-3). Atherosclerosis is the major underlying cause of CVD and is [...]

Published
2017
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200. Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes

Author

Akbari, Parsa, Sosina, Olukayode A., Bovijn, Jonas, Landheer, Karl, Nielsen, Jonas B., Kim, Minhee, Aykul, Senem, De, Tanima, Haas, Mary E., Hindy, George, Lin, Nan, Dinsmore, Ian R., Luo, Jonathan Z., Hectors, Stefanie, Geraghty, Benjamin, Germino, Mary, Panagis, Lampros, Parasoglou, Prodromos, Walls, Johnathon R., Halasz, Gabor, Atwal, Gurinder S., Della Gatta, Giusy, Jones, Marcus, LeBlanc, Michelle G., Still, Christopher D., Carey, David J., Giontella, Alice, Orho-Melander, Marju, Berumen, Jaime, Kuri-Morales, Pablo, Alegre-Díaz, Jesus, Torres, Jason M., Emberson, Jonathan R., Collins, Rory, Rader, Daniel J., Zambrowicz, Brian, Murphy, Andrew J., Balasubramanian, Suganthi, Overton, John D., Reid, Jeffrey G., Shuldiner, Alan R., Cantor, Michael, Abecasis, Goncalo R., Ferreira, Manuel A. R., Sleeman, Mark W., Gusarova, Viktoria, Altarejos, Judith, Harris, Charles, Economides, Aris N., Idone, Vincent, Karalis, Katia, Mirshahi, Tooraj, Yancopoulos, George D., Melander, Olle, Marchini, Jonathan, Tapia-Conyer, Roberto, Locke, Adam E., Baras, Aris, Verweij, Niek, and Lotta, Luca A.

Subjects
Multidisciplinary, Adipose Tissue, Diabetes Mellitus, Type 2, Mutation, Humans, General Physics and Astronomy, Exome, General Chemistry, General Biochemistry, Genetics and Molecular Biology, Adiposity, Inhibin-beta Subunits
Abstract

Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution (p = 1.8 × 10−09), favorable metabolic profile and protection from type 2 diabetes (~28% lower odds; p = 0.004) for heterozygous protein-truncating mutations in INHBE, which encodes a circulating growth factor of the activin family, highly and specifically expressed in hepatocytes. Our results suggest that inhibin βE is a liver-expressed negative regulator of adipose storage whose blockade may be beneficial in fat distribution-associated metabolic disease.

Published
2022

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