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159 results on '"Hilchey, Shannon P."'

10. Cyclosporine A Modulates LSP1 Protein Levels in Human B Cells to Attenuate B Cell Migration at Low O 2 Levels.

Author

Hilchey, Shannon P., Palshikar, Mukta G., Mendelson, Eric S., Shen, Shichen, Rasam, Sailee, Emo, Jason A., Qu, Jun, Thakar, Juilee, and Zand, Martin S.

Subjects
*CELL migration, *LYMPHOID tissue, *CXCR4 receptors, *CYCLOSPORINE, *CHEMOTAXIS, *B cells, *ANTIBODY formation
Abstract

Coordinated migration of B cells within and between secondary lymphoid tissues is required for robust antibody responses to infection or vaccination. Secondary lymphoid tissues normally expose B cells to a low O 2 (hypoxic) environment. Recently, we have shown that human B cell migration is modulated by an O 2 -dependent molecular switch, centrally controlled by the hypoxia-induced (transcription) factor-1 α (HIF1A), which can be disrupted by the immunosuppressive calcineurin inhibitor, cyclosporine A (CyA). However, the mechanisms by which low O 2 environments attenuate B cell migration remain poorly defined. Proteomics analysis has linked CXCR4 chemokine receptor signaling to cytoskeletal rearrangement. We now hypothesize that the pathways linking the O 2 sensing molecular switch to chemokine receptor signaling and cytoskeletal rearrangement would likely contain phosphorylation events, which are typically missed in traditional transcriptomic and/or proteomic analyses. Hence, we have performed a comprehensive phosphoproteomics analysis of human B cells treated with CyA after engagement of the chemokine receptor CXCR4 with CXCL12. Statistical analysis of the separate and synergistic effects of CyA and CXCL12 revealed 116 proteins whose abundance is driven by a synergistic interaction between CyA and CXCL12. Further, we used our previously described algorithm BONITA to reveal a critical role for Lymphocyte Specific Protein 1 (LSP1) in cytoskeletal rearrangement. LSP1 is known to modulate neutrophil migration. Validating these modeling results, we show experimentally that LSP1 levels in B cells increase with low O 2 exposure, and CyA treatment results in decreased LSP1 protein levels. This correlates with the increased chemotactic activity observed after CyA treatment. Lastly, we directly link LSP1 levels to chemotactic capacity, as shRNA knock-down of LSP1 results in significantly increased B cell chemotaxis at low O 2 levels. These results directly link CyA to LSP1-dependent cytoskeletal regulation, demonstrating a previously unrecognized mechanism by which CyA modulates human B cell migration. Data are available via ProteomeXchange with identifier PXD036167. [ABSTRACT FROM AUTHOR]

Published
2022
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17. WikiNetworks: translating manually created biological pathways for topological analysis.

Author

Palshikar, Mukta G, Hilchey, Shannon P, Zand, Martin S, and Thakar, Juilee

Subjects
*BIOLOGICAL databases, *DATA analysis, *BIOINFORMATICS, *ANNOTATIONS
Abstract

Summary WikiPathways is a database of 2979 biological pathways across 31 species created using the drawing software PathVisio. Many of these pathways are not directly usable for network-based topological analyses due to differences in curation styles and drawings. We developed the WikiNetworks package to standardize and construct directed networks by combining geometric information and manual annotations from WikiPathways. WikiNetworks performs significantly better than existing tools. This enables the use of high-quality WikiPathways resource for network-based topological analysis of high-throughput data. Availability and implementation WikiNetworks is written in Python3 and is available on github.com/Thakar-Lab/wikinetworks and on PyPI. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Published
2022
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18. Surfactant Cocktail-Aided Extraction/Precipitation/On-Pellet Digestion Strategy Enables Efficient and Reproducible Sample Preparation for Large-Scale Quantitative Proteomics

Author

Shen, Shichen, primary, An, Bo, additional, Wang, Xue, additional, Hilchey, Shannon P., additional, Li, Jun, additional, Cao, Jin, additional, Tian, Yu, additional, Hu, Chenqi, additional, Jin, Liang, additional, Ng, Andrew, additional, Tu, Chengjian, additional, Qu, Miao, additional, Zand, Martin S., additional, and Qu, Jun, additional

Published
2018
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19. Broad cross-reactive IgG responses elicited by adjuvanted vaccination with recombinant influenza hemagglutinin (rHA) in ferrets and mice

Author

Wang, Jiong, primary, Hilchey, Shannon P., additional, DeDiego, Marta, additional, Perry, Sheldon, additional, Hyrien, Ollivier, additional, Nogales, Aitor, additional, Garigen, Jessica, additional, Amanat, Fatima, additional, Huertas, Nelson, additional, Krammer, Florian, additional, Martinez-Sobrido, Luis, additional, Topham, David J., additional, Treanor, John J., additional, Sangster, Mark Y., additional, and Zand, Martin S., additional

Published
2018
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22. Follicular Lymphoma Tregs Have a Distinct Transcription Profile Impacting Their Migration and Retention in the Malignant Lymph Node

Author

Nedelkovska, Hristina, primary, Rosenberg, Alexander F., additional, Hilchey, Shannon P., additional, Hyrien, Ollivier, additional, Burack, W. Richard, additional, Quataert, Sally A., additional, Baker, Christina M., additional, Azadniv, Mitra, additional, Welle, Stephen L., additional, Ansell, Stephen M., additional, Kim, Minsoo, additional, and Bernstein, Steven H., additional

Published
2016
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27. Human Follicular Lymphoma CD39+-Infiltrating T Cells Contribute to Adenosine-Mediated T Cell Hyporesponsiveness1

Author

Hilchey, Shannon P., Kobie, James J., Cochran, Mathew R., Secor-Socha, Shelley, Wang, Jyh-Chiang E., Hyrien, Ollivier, Burack, W. Richard, Mosmann, Tim R., Quataert, Sally A., and Bernstein, Steven H.

Subjects
Clonal Anergy, Adenosine, Triazines, Apyrase, Receptors, Purinergic P1, CD8-Positive T-Lymphocytes, Triazoles, T-Lymphocytes, Regulatory, Article, Interferon-gamma, Adenosine Triphosphate, Lymphocytes, Tumor-Infiltrating, Neuroprotective Agents, Pyrimidines, Antigens, CD, Humans, Interleukin-2, Lymphoma, Follicular
Abstract

Our previous work has demonstrated that human follicular lymphoma (FL) infiltrating T cells are anergic, in part due to suppression by regulatory T cells. In this study, we identify pericellular adenosine, interacting with T cell-associated G protein-coupled A(2A/B) adenosine receptors (AR), as contributing to FL T cell hyporesponsiveness. In a subset of FL patient samples, treatment of lymph node mononuclear cells (LNMC) with specific A(2A/B) AR antagonists results in an increase in IFN-gamma or IL-2 secretion upon anti-CD3/CD28 Ab stimulation, as compared with that seen without inhibitors. In contrast, treatment with an A(1) AR antagonist had no effect on cytokine secretion. As the rate limiting step for adenosine generation from pericellular ATP is the ecto-ATPase CD39, we next show that inhibition of CD39 activity using the inhibitor ARL 67156 partially overcomes T cell hyporesponsiveness in a subset of patient samples. Phenotypic characterization of LNMC demonstrates populations of CD39-expressing CD4(+) and CD8(+) T cells, which are overrepresented in FL as compared with that seen in normal or reactive nodes, or normal peripheral blood. Thirty percent of the FL CD4(+)CD39(+) T cells coexpress CD25(high) and FOXP3 (consistent with regulatory T cells). Finally, FL or normal LNMC hydrolyze ATP in vitro, in a dose- and time-dependent fashion, with the rate of ATP consumption being associated with the degree of CD39(+) T cell infiltration. Together, these results support the finding that the ATP-ectonucleotidase-adenosine system mediates T cell anergy in a human tumor. In addition, these studies suggest that the A(2A/B) AR as well as CD39 are novel pharmacological targets for augmenting cancer immunotherapy.

Published
2009

28. Modeling the Dynamics and Migratory Pathways of Virus-Specific Antibody-Secreting Cell Populations in Primary Influenza Infection

Author

Miao, Hongyu, primary, Sangster, Mark Y., additional, Livingstone, Alexandra M., additional, Hilchey, Shannon P., additional, Zhang, Le, additional, Topham, David J., additional, Mosmann, Tim R., additional, Holden-Wiltse, Jeanne, additional, Perelson, Alan S., additional, Wu, Hulin, additional, and Zand, Martin S., additional

Published
2014
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32. Comprehensive in Vitro and in Vivo Analysis of Phosphatidylinositol-3-Kinase Delta (PI3Kδ) Inhibition Using GS-1101 (CAL-101) in Combination with Mammalian Target of Rapamycin (mTOR) Inhibition Using Temsirolimus or Everolimus in Mantle Cell Lymphoma (MCL)

Author

Barr, Paul M., primary, Hernandez-Ilizaliturri, Francisco J., additional, Murante, Thomas, additional, Hilchey, Shannon P., additional, Peterson, Derick R, additional, Kelly, Jennifer L., additional, Johnson, Dave M., additional, Lannutti, Brian J., additional, Czuczman, Myron S., additional, Friedberg, Jonathan W., additional, and Bernstein, Steven H., additional

Published
2012
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36. Follicular lymphoma tumor–infiltrating T-helper (TH) cells have the same polyfunctional potential as normal nodal TH cells despite skewed differentiation

Author

Hilchey, Shannon P., primary, Rosenberg, Alexander F., additional, Hyrien, Ollivier, additional, Secor-Socha, Shelley, additional, Cochran, Matthew R., additional, Brady, Michael T., additional, Wang, Jyh-Chiang E., additional, Sanz, Iñaki, additional, Burack, W. Richard, additional, Quataert, Sally A., additional, and Bernstein, Steven H., additional

Published
2011
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37. Follicular Lymphoma Tumor Infiltrating T-Helper (Th) Cells Have the Same Intrinsic Polyfunctional Response Potential Upon Stimulation as Do Reactive and Normal Lymph Node Th Cells Despite Having Skewed Differentiation; Implications for Immunotherapy

Author

Hilchey, Shannon P., primary, Rosenberg, Alexander F., additional, Hyrien, Ollivier, additional, Secor-Socha, Shelley, additional, Cochran, Matthew R., additional, Burack, W. Richard, additional, Wang, Jyh-Chiang E., additional, Quataert, Sally A., additional, and Bernstein, Steven H., additional

Published
2010
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40. Increased Proportions of CD39+ Infiltrating T-Cells Contribute to Adenosine Mediated T-Cell Hypo-Responsiveness within Human Follicular Lymphoma.

Author

Hilchey, Shannon P., primary, Kobie, James J., additional, Cochran, Matthew R., additional, Secor-Socha, Shelley, additional, Wang, Jyh-Chiang E., additional, Hyrien, Ollivier, additional, Burack, W. Richard, additional, Mosmann, Tim R., additional, Quataert, Sally A., additional, and Bernstein, Steven H., additional

Published
2009
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46. Ion-Current-Based Temporal Proteomic Profiling of Influenza-A-Virus-Infected Mouse Lungs Revealed Underlying Mechanisms of Altered Integrity of the Lung Microvascular Barrier

Author

Shen, Shichen, Li, Jun, Hilchey, Shannon, Shen, Xiaomeng, Tu, Chengjian, Qiu, Xing, Ng, Andrew, Ghaemmaghami, Sina, Wu, Hulin, Zand, Martin S., and Qu, Jun

Abstract

Investigation of influenza-A-virus (IAV)-infected lung proteomes will greatly promote our understanding on the virus-host crosstalk. Using a detergent-cocktail extraction and digestion procedure and a reproducible ion-current-based method, we performed the first comprehensive temporal analysis of mouse IAV infection. Mouse lung tissues at three time points post-inoculation were compared with controls (n= 4/group), and >1600 proteins were quantified without missing value in any animal. Significantly changed proteins were identified at 4 days (n= 144), 7 days (n= 695), and 10 days (n= 396) after infection, with low false altered protein rates (1.73–8.39%). Functional annotation revealed several key biological processes involved in the systemic host responses. Intriguingly, decreased levels of several cell junction proteins as well as increased levels of tissue metalloproteinase MMP9 were observed, reflecting the IAV-induced structural breakdown of lung epithelial barrier. Supporting evidence of MMP9 activation came from immunoassays examining the abundance and phosphorylation states of all MAPKs and several relevant molecules. Importantly, IAV-induced MMP gelatinase expression was suggested to be specific to MMP9, and p38 MAPK may contribute predominantly to MMP9 elevation. These findings help to resolve the long-lasting debate regarding the signaling pathways of IAV-induced MMP9 expression and shed light on the molecular mechanisms underlying pulmonary capillary-alveolar leak syndrome that can occur during influenza infection.

Published
2016
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50. Follicular lymphoma tumor-infiltrating T-helper (TH) cells have the same polyfunctional potential as normal nodal TH cells despite skewed differentiation.

Author

Hilchey, Shannon P., Rosenberg, Alexander F., Hyrien, Ollivier, Secor-Socha, Shelley, Cochran, Matthew R., Brady, Michael T., Wang, Jyh-Chiang E., Sanz, Iñaki, Burack, W. Richard, Quataert, Sally A., and Bernstein, Steven H.

Subjects
*T cells, *FACTOR analysis, *TRANSCRIPTION factors, *LYMPH nodes, *TUMORS, *STAPHYLOCOCCUS
Abstract

The follicular lymphoma (FL) T-cell microenvironment plays a critical role in the biology of this disease. We therefore determined the lineage, differentiation state, and functional potential of FL-infiltrating CD4+ T-helper cells (TH) compared with reactive and normal lymph node (NLN) TH cells. Relative to NLNs, FL cells have decreased proportions of naive and central memory but increased proportions of effector memory TH cells. We further show differences in the distribution and anatomical localization of CXCR5+ TH populations that, on the basis of transcription factor analysis, include both regulatory and follicular helper T cells. On Staphylococcus enterotoxin-B stimulation, which stimulates T cells through the T-cell receptor, requires no processing by APCs, and can overcome regulator T cell-mediated suppression, the proportion of uncommitted primed precursor cells, as well as TH2 and TH17 cells is higher in FL cells than in reactive lymph nodes or NLNs. However, the proportion of TH1 and polyfunctional TH cells (producing multiple cytokines simultaneously) is similar in FL cells and NLNs. These data suggest that, although TH-cell differentiation in FL is skewed compared with NLNs, FL TH cells should have the same intrinsic ability to elicit antitumor effector responses as NLN TH cells when tumor suppressive mechanisms are attenuated. [ABSTRACT FROM AUTHOR]

Published
2011
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