7 results on '"Kimberly Argueta"'
Search Results
2. Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
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Girish Nadkarni, Ishan Paranjpe, Pushkala Jayaraman, Chen-Yang Su, Sirui Zhou, Steven Chen, Diane Del Valle, Ryan Thompson, Ephraim Kenigsberg, Shan Zhao, Suraj Jaladanki, Kumardeep Chaudhary, Steven Ascolillo, Akhil Vaid, Edgar Gonzalez-Kozlova, Arvind Kumar, Manish Paranjpe, Ross O'Hagan, Samir Kamat, Faris Gulamali, Justin Kauffman, Hui Xie, Joceyln Harris, Manishkumar Patel, Kimberly Argueta, Craig Batchelor, Kai Nie, Sergio Dellepiane, Leisha Scott, Matthew Levin, John He, Mayte Suárez-Fariñas, Steven Coca, Lili Chan, Evren Azeloglu, Eric Schadt, Noam Beckmann, Sacha Gnjatic, Miriam Merad, Seunghee Kim-Schulze, J. Brent Richards, Benjamin Glicksberg, and Alexander Charney
- Abstract
Background Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Methods Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437), we identified 413 higher plasma abundances of protein targets and 40 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p Results We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-Cindicating tubular dysfunction and injury. Conclusions Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.
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- 2021
3. Circulating proteins to predict adverse COVID-19 outcomes
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Edgar Gonzalez-Kozlova, David R. Morrison, Branka Vulesevic, Nofar Kimchi, Robert Marvin, Maik Pietzner, Zaman Afrasiabi, Kimberly Argueta, Louis Petitjean, Naomi Duggan, Ryan Thompson, Meriem Bouab, Manishkumar Patel, Kevin Tuballes, Ieisha Scott, J. Brent Richards, Mario A. Cedillo, Nicole W. Simons, Jocelyn Harris, Tala Abdullah, Claudia Langenberg, Danielle Henry, Vincenzo Forgetta, Daniel Kaufmann, Madeleine Durand, Chen-Yang Su Mr., Michael A Hinterberg, Elsa Brunet-Ratnasingham, Celia M. T. Greenwood, Miriam Merad, Wonseok Jeon, Alexander W. Charney, Sacha Gnjatic, Noam D. Beckmann, Xiaoqing Xue, Nicolas Zaki, Julia Carrasco-Zanini, Diane Marie Del Valle, Joelle Pineau, Esther Cheng, Tomoko Nakanishi, Olumide Adeleye, Kai Nie, Chantal DeLuca, Konstantinos Mouskas, Thomas U. Marron, Marc Afilalo, Guillaume Butler-Laporte, Yiheng Chen, Yossi Farjoun, Yara Moussa, Vincent Mooser, Eric E. Schadt, Clare Paterson, Noor Almamlouk, Chris Tselios, Nathalie Brassard, Sirui Zhou, Hui Xie, Ephraim Kenigsberg, Nardin Rezk, Seunghee Kim-Schulze, Laetitia Laurent, Charlotte Guzman, Erwin Schurr, and Joanthan Afilalo
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Oncology ,medicine.medical_specialty ,Receiver operating characteristic ,Coronavirus disease 2019 (COVID-19) ,business.industry ,medicine.medical_treatment ,Disease progression ,Age and sex ,Cytokine ,Internal medicine ,Cohort ,Medicine ,Generalizability theory ,business ,Predictive modelling - Abstract
Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4,701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict adverse COVID-19 outcomes in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4,701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different adverse COVID-19 outcomes were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of adverse COVID-19 outcomes. Further research is needed to understand how to incorporate protein measurement into clinical care.
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- 2021
4. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children
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Noam D. Beckmann, Nancy J. Francoeur, Diane Marie Del Valle, Gurpawan Kang, Anh Do, Emily Moya, Lillian Wilkins, Jessica Le Berichel, Christie Chang, Robert Marvin, Sharlene Calorossi, Phillip H. Comella, Alona Lansky, Laura Walker, Nancy Yi, Alex Yu, Jonathan Chung, Matthew Hartnett, Melody Eaton, Sandra Hatem, Hajra Jamal, Alara Akyatan, Esther Cheng, Alexandra Tabachnikova, Lora E. Liharska, Liam Cotter, Brian Fennessy, Akhil Vaid, Guillermo Barturen, Hardik Shah, Ying-chih Wang, Shwetha Hara Sridhar, Juan Soto, Lauren Lepow, Swaroop Bose, Kent Madrid, Ethan Ellis, Elyze Merzier, Konstantinos Vlachos, Nataly Fishman, Manying Tin, Melissa Smith, Hui Xie, Manishkumar Patel, Aviva G. Beckmann, Kai Nie, Kimberly Argueta, Jocelyn Harris, Neha Karekar, Craig Batchelor, Jose Lacunza, Mahlet Yishak, Kevin Tuballes, Ieisha Scott, Arvind Kumar, Scott R. Tyler, Suraj Jaladanki, Charuta Agashe, Ryan Thompson, Evan Clark, Bojan Losic, Lauren Peters, The Mount Sinai COVID-19 Biobank Team, Panagiotis Roussos, Jun Zhu, Wenhui Wang, Konstantinos Mouskas, Andrew Kasarskis, Benjamin S. Glicksberg, Girish Nadkarni, Dusan Bogunovic, Cordelia Elaiho, Sandeep Gangadharan, George Ofori-Amanfo, Kasey Alesso-Carra, Kenan Onel, Karen M. Wilson, Nicole W. Simons, Carmen Argmann, Supinda Bunyavanich, Marta E. Alarcón-Riquelme, Thomas U. Marron, Adeeb Rahman, Seunghee Kim-Schulze, Sacha Gnjatic, Bruce D. Gelb, Miriam Merad, Robert Sebra, Gabriel E. Hoffman, Eric E. Schadt, and Alexander W. Charney
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Male ,TBX21 ,Cell type ,Adolescent ,Science ,Down-Regulation ,General Physics and Astronomy ,Inflammation ,CD8-Positive T-Lymphocytes ,Mucocutaneous Lymph Node Syndrome ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Pathogenesis ,Transcriptome ,Young Adult ,CD57 Antigens ,Downregulation and upregulation ,otorhinolaryngologic diseases ,medicine ,Humans ,Cytotoxic T cell ,Child ,Multidisciplinary ,SARS-CoV-2 ,Infant, Newborn ,COVID-19 ,Infant ,General Chemistry ,CD56 Antigen ,Systemic Inflammatory Response Syndrome ,Killer Cells, Natural ,Child, Preschool ,Immunology ,Female ,medicine.symptom ,CD8 - Abstract
Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C., Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.
- Published
- 2021
5. Abstract 5026: Dynamic changes in circulating protein levels reveal an association between ipilimumab and nivolumab combination treatment (SWOG Lung-MAP S1400I trial) with outcomes in squamous cell lung cancer
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Edgar Gonzalez-Kozlova, Hsin-Hui Huang, Mary Redman, Roy Herbst, Scott Gettinger, Luda Bazhenova, Hui Xie, Manishkumar Patel, Kai Nie, Jocelyn Harris, Kimberly Argueta, Karen Kelly, Ethan Cerami, James Lindsay, Joyce Yu, Roshni Biswas, Stephen Van Nostrand, Radim Moravec, Diane Marie Del Valle, Seunghee Kim-schulze, and Sacha Gnjatic
- Subjects
Cancer Research ,Oncology - Abstract
Squamous cell lung cancer (SqCLC) is a type of non-small cell lung cancer strongly associated with cigarette smoking and with known targetable mutations, however some patients do not have matching targeted drugs. The S1400I Phase III randomized LungMap sub-study of nivo+ipi versus nivo accrued 275 (252 eligible) previously-treated patients with stage IV SqCLC and absence of matched mutations (NCT02154490).Here, to investigate the longitudinal (baseline, C2 week 3, C4 week 7, C5 week 9) serum protein changes associated with treatment or response, we performed Olink proximity extension assay in 160 patients (561 samples) using an immuno-oncology panel of 92 analytes. We utilized mixed linear and joint models to identify differentially expressed proteins between treatment arms (nivo vs. nivo+ipi), response and quantify the effect of other potential prognostic factors. This approach quantifies the effect of covariates such as smoking status, demographics, prior radiation therapy, and metastases. We jointly modeled expression and survival to identify changes in proteins over time. The thresholds for significance in differentially expression tests were a log fold change of at least 0.5 and a false discovery rate of under 0.05 (FDR as a multiple testing adjustment method). The joint models used thresholds of log fold change of more than 1 and hazard ratio of more than 1. Results revealed increases in 40 serum proteins after treatment with either nivo alone or combined with ipi, including CXCL9, CXCL10, CXCL11, CXCL13, IL6, IL8, IL10, IFNg, and soluble PD-L1 and PDCD1. nivo+ipi treatment showed greater increases in IL8 and CXCL13 post-treatment compared to nivo alone. In addition, circulating IL6, CXCL13, and MIC-A/B were higher in patients with stable or progressive disease compared to those with objective response after treatment. The joint model revealed a worse hazard ratio with increases in 10 soluble proteins, including IL6, IL8, and CXCL13. Finally, for patients with similar values of IL8, those treated by combination had a better survival outcome than those treated by nivo alone. Using a data-modeling approach, we identified significant longitudinal changes in 40 serum proteins out of 92 tested in patients with SqCLC treated with nivo or nivo+ipi. Increases in serum inflammatory markers IL6 and CXCL13 were associated with worse disease. Although overall survival was not statistically different between arms, our modeling approaches suggested that IL-8 monitoring may help identify patients benefiting more from the combination vs. nivo alone. Citation Format: Edgar Gonzalez-Kozlova, Hsin-Hui Huang, Mary Redman, Roy Herbst, Scott Gettinger, Luda Bazhenova, Hui Xie, Manishkumar Patel, Kai Nie, Jocelyn Harris, Kimberly Argueta, Karen Kelly, Ethan Cerami, James Lindsay, Joyce Yu, Roshni Biswas, Stephen Van Nostrand, Radim Moravec, Diane Marie Del Valle, Seunghee Kim-schulze, Sacha Gnjatic. Dynamic changes in circulating protein levels reveal an association between ipilimumab and nivolumab combination treatment (SWOG Lung-MAP S1400I trial) with outcomes in squamous cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5026.
- Published
- 2022
6. Dynamic changes in serum analyte levels associated with clinical outcome in squamous cell lung cancer trial SWOG Lung-MAP S1400I of nivolumab ± ipilimumab
- Author
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Edgar Gonzalez-Kozlova, Hsin-Hui Huang, Mary Weber Redman, Roy S. Herbst, Scott N. Gettinger, Lyudmila Bazhenova, Hui Xie, Manishkumar Patel, Kai Nie, Jocelyn Harris, Kimberly Argueta, Ethan Cerami, Joyce Hong, Roshni Biswas, Stephen Van Nostrand, Karen Kelly, Radim Moravec, Diane Del Valle, Seunghee Kim-Schulze, and Sacha Gnjatic
- Subjects
Cancer Research ,Oncology - Abstract
9044 Background: While Immune checkpoint blockade (ICB) is standard treatment for lung cancer there are limited biomarkers that predict benefit, pharmacokinetic on-treatment activity or explain progression. S1400I was a randomized Phase III trial of nivolumab(N)+ipilimumab(I) versus N (NCT02154490, PMID 34264316) for ICB naïve, previously treated stage IV or recurrent squamous cell lung cancer. We performed circulating serum protein analysis of serial blood specimens from patients enrolled in S1400I to evaluate if serum proteins levels changed over time, changes differed by treatment arm, and if they were associated with overall survival. Methods: 561 serial blood specimens (baseline, weeks (wk) 3, 7, 9, and progression [PD]) from 160 of 252 eligible patients enrolled to S1400I were analyzed for 92 immuno-oncology analytes with the Olink proximity extension assay. Protein levels were normalized with use of internal controls and quantified as log2 protein expression (denoted as NPX). Linear mixed models evaluated change in expression from baseline at each time point (wks 3,7,9 and PD), and NPX differences at baseline, wk3, and PD depending on best objective response. A Cox model was used to evaluate the association between baseline NPX and survival. Overall survival and longitudinal cytokine expression were jointly modeled using a linear mixed model to estimate dynamic biomarker changes in NPX and a Cox model for survival. The joint models for time-varying NPX values included a random intercept and modeled time using a natural spline with three knots. Significance was defined as P < 0.05. Results: Serum proteins PCDC1, CXCL9, and CXCL10 were increased from baseline at wks 3,7,9 and at PD. CCL19 was increased at wks 3 and 7 but not at wk 9 and PD. IL10 and IFNγ were increased at wk 3 but subsequently returned to baseline. Change in CXCL13 from baseline to PD was larger for N+I versus N. Baseline CCL23, CSF-1, IL6, and MUC-16 were associated with shorter survival (HR > 1). Joint modeling of survival with cytokines showed an increased risk of death (HR > 1) with higher longitudinal serum levels of CXCL13, MMP12, CSF-1, and IL8. Patients achieving objective response had higher IL4 and LAMP3 and lower IL6 and IL8 at baseline and wk 3 compared to non-responders. Conclusions: Measurements of blood circulating soluble proteins represent easily accessible biomarkers that may be useful as indicators of outcome, and that will need to be prospectively confirmed. Clinical trial information: NCT02154490.
- Published
- 2022
7. Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children
- Author
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Sandeep Gangadharan, Matthew Harnett, Ryan Thompson, Seunghee Kim-Schulze, Liam Cotter, Melody Eaton, Robert Sebra, Konstantinos Vlachos, Karen M. Wilson, Nicole W. Simons, Jocelyn Harris, Manying Tin, Hardik Shah, Nancy Yi, Scott R. Tyler, Emily Moya, Leisha Scott, Brian Fennessey, Arvind Kumar, Guillermo Barturen, Konstantinos Mouskas, Benjamin S. Glicksberg, Elyze Merzier, Kasey Alesso-Carra, Diane Marie Del Valle, Kevin Tuballes, Alona Lansky, Bojan Losic, Cordelia Elaiho, Yinh-chih Wang, Jessica Le Berichel, Aviva G. Beckmann, Akhil Vaid, Suraj K. Jaladanki, Lora Liharska, Noam D. Beckmann, Hui Xie, Christie Chang, Laura Walker, Mahlet Yishak, Marta E. Alarcón-Riquelme, Evan Clark, Esther Cheng, Bruce D. Gelb, Hajra Jamal, Kent Madrid, Alara Akyatan, Sharlene Calorossi, Carmen Argmann, Craig Batchelor, Kimberly Argueta, Jose Lacunza, Lauren Lepow, Andrew Kasarskis, Gabriel E. Hoffman, Eric E. Schadt, Miriam Merad, Nancy Francoeur, Wenhui Wang, Alexander W. Charney, Sacha Gnjatic, Neha Karekar, Melissa Smith, Sandra Hatem, Thomas U. Marron, Shwetha Hara Sridhar, Ethan Ellis, Kenan Onel, Girish N. Nadkarni, Jun Zhu, Manishkumar Patel, Lillian Wilkins, George Ofori-Amanfo, Swaroop Bose, Robert Marvin, Alex J. Yu, Nataly Fishman, Gurpawan Kang, Phillip H. Comella, Alexandra Tabachnikova, Juan C. Diaz Soto, Adeeb Rahman, and Dusan Bogunovic
- Subjects
TBX21 ,Male ,Cell type ,pediatrics ,Adolescent ,Lymphocyte ,Systems analysis ,Down-Regulation ,Inflammation ,MIS-C ,CD8-Positive T-Lymphocytes ,Mucocutaneous Lymph Node Syndrome ,Article ,Transcriptome ,Prognostic markers ,Young Adult ,CD57 Antigens ,medicine ,otorhinolaryngologic diseases ,Cytotoxic T cell ,Humans ,Child ,business.industry ,SARS-CoV-2 ,Infant, Newborn ,COVID-19 ,Infant ,Antimicrobial responses ,medicine.disease ,CD56 Antigen ,Systemic Inflammatory Response Syndrome ,Killer Cells, Natural ,medicine.anatomical_structure ,Child, Preschool ,Immunology ,Kawasaki disease ,Female ,medicine.symptom ,business ,CD8 - Abstract
Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C., Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.
- Published
- 2020
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