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23 results on '"Hesterberg, Rebecca S."'

2. BatchFLEX: feature-level equalization of X-batch.

Author

Davis, Joshua T, Obermayer, Alyssa N, Soupir, Alex C, Hesterberg, Rebecca S, Duong, Thac, Yang, Ching-Yao, Dao, Ken Phong, Manley, Brandon J, Grass, G Daniel, Avram, Dorina, Rodriguez, Paulo C, Fridley, Brooke L, Yu, Xiaoqing, Teng, Mingxiang, Wang, Xuefeng, and Shaw, Timothy I

Subjects
GENE expression, SAMPLING (Process), RNA, MOTIVATION (Psychology), MOBILE apps
Abstract

Motivation Integrative analysis of heterogeneous expression data remains challenging due to variations in platform, RNA quality, sample processing, and other unknown technical effects. Selecting the approach for removing unwanted batch effects can be a time-consuming and tedious process, especially for more biologically focused investigators. Results Here, we present BatchFLEX, a Shiny app that can facilitate visualization and correction of batch effects using several established methods. BatchFLEX can visualize the variance contribution of a factor before and after correction. As an example, we have analyzed ImmGen microarray data and enhanced its expression signals that distinguishes each immune cell type. Moreover, our analysis revealed the impact of the batch correction in altering the gene expression rank and single-sample GSEA pathway scores in immune cell types, highlighting the importance of real-time assessment of the batch correction for optimal downstream analysis. Availability and implementation Our tool is available through Github https://github.com/shawlab-moffitt/BATCH-FLEX-ShinyApp with an online example on Shiny.io https://shawlab-moffitt.shinyapps.io/batch_flex/. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Cereblon harnesses Myc-dependent bioenergetics and activity of CD8+ T lymphocytes

Author

Hesterberg, Rebecca S., Beatty, Matthew S., Han, Ying, Fernandez, Mario R., Akuffo, Afua A., Goodheart, William E., Yang, Chunying, Chang, Shiun, Colin, Christelle M., Alontaga, Aileen Y., McDaniel, Jessica M., Mailloux, Adam W., Billington, Julia M.R., Yue, Lanzhu, Russell, Shonagh, Gillies, Robert J., Yun, Sang Y., Ayaz, Muhammad, Lawrence, Nicholas J., Lawrence, Harshani R., Yu, Xue-Zhong, Fu, Jianing, Darville, Lancia N., Koomen, John M., Ren, Xiubao, Messina, Jane, Jiang, Kun, Garrett, Timothy J., Rajadhyaksha, Anjali M., Cleveland, John L., and Epling-Burnette, Pearlie K.

Published
2020
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4. Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8+T cells to suppress anti-tumor immunity

Author

Tejero, Joanne D., primary, Hesterberg, Rebecca S., additional, Drapela, Stanislav, additional, Ilter, Didem, additional, Raizada, Devesh, additional, Lazure, Felicia, additional, Kashfi, Hossein, additional, Liu, Min, additional, Fernández-García, Juan, additional, Asara, John M., additional, Fendt, Sarah-Maria, additional, Cleveland, John L., additional, and Gomes, Ana P., additional

Published
2024
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5. Ligand-mediated protein degradation reveals functional conservation among sequence variants of the CUL4-type E3 ligase substrate receptor cereblon

Author

Akuffo, Afua A., Alontaga, Aileen Y., Metcalf, Rainer, Beatty, Matthew S., Becker, Andreas, McDaniel, Jessica M., Hesterberg, Rebecca S., Goodheart, William E., Gunawan, Steven, Ayaz, Muhammad, Yang, Yan, Karim, Md Rezaul, Orobello, Morgan E., Daniel, Kenyon, Guida, Wayne, Yoder, Jeffrey A., Rajadhyaksha, Anjali M., Schönbrunn, Ernst, Lawrence, Harshani R., Lawrence, Nicholas J., and Epling-Burnette, Pearlie K.

Published
2018
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6. Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells

Author

Elmarsafawi, Aya G., primary, Hesterberg, Rebecca S., additional, Fernandez, Mario R., additional, Yang, Chunying, additional, Darville, Lancia N.F., additional, Liu, Min, additional, Koomen, John M., additional, Phanstiel, Otto, additional, Atkins, Reginald, additional, Mullinax, John E., additional, Pilon-Thomas, Shari A., additional, Locke, Frederick L., additional, Epling-Burnette, Pearlie K., additional, and Cleveland, John L., additional

Published
2023
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7. Supplementary Figure from TCR-Independent Metabolic Reprogramming Precedes Lymphoma-Driven Changes in T-cell Fate

Author

Hesterberg, Rebecca S., primary, Liu, Min, primary, Elmarsafawi, Aya G., primary, Koomen, John M., primary, Welsh, Eric A., primary, Hesterberg, Stephen G., primary, Ranatunga, Sujeewa, primary, Yang, Chunying, primary, Li, Weimin, primary, Lawrence, Harshani R., primary, Rodriguez, Paulo C., primary, Berglund, Anders E., primary, and Cleveland, John L., primary

Published
2023
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8. Data from TCR-Independent Metabolic Reprogramming Precedes Lymphoma-Driven Changes in T-cell Fate

Author

Hesterberg, Rebecca S., primary, Liu, Min, primary, Elmarsafawi, Aya G., primary, Koomen, John M., primary, Welsh, Eric A., primary, Hesterberg, Stephen G., primary, Ranatunga, Sujeewa, primary, Yang, Chunying, primary, Li, Weimin, primary, Lawrence, Harshani R., primary, Rodriguez, Paulo C., primary, Berglund, Anders E., primary, and Cleveland, John L., primary

Published
2023
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9. Supplementary Table from TCR-Independent Metabolic Reprogramming Precedes Lymphoma-Driven Changes in T-cell Fate

Author

Hesterberg, Rebecca S., primary, Liu, Min, primary, Elmarsafawi, Aya G., primary, Koomen, John M., primary, Welsh, Eric A., primary, Hesterberg, Stephen G., primary, Ranatunga, Sujeewa, primary, Yang, Chunying, primary, Li, Weimin, primary, Lawrence, Harshani R., primary, Rodriguez, Paulo C., primary, Berglund, Anders E., primary, and Cleveland, John L., primary

Published
2023
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11. Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8+T cells to suppress anti-tumor immunity

Author

Tejero, Joanne D., Hesterberg, Rebecca S., Drapela, Stanislav, Ilter, Didem, Raizada, Devesh, Lazure, Felicia, Kashfi, Hossein, Liu, Min, Silvane, Leonardo, Avram, Dorina, Fernández-García, Juan, Asara, John M., Fendt, Sarah-Maria, Cleveland, John L., and Gomes, Ana P.

Abstract

Systemic levels of methylmalonic acid (MMA), a byproduct of propionate metabolism, increase with age and MMA promotes tumor progression via its direct effects in tumor cells. However, the role of MMA in modulating the tumor ecosystem remains to be investigated. The proliferation and function of CD8+T cells, key anti-tumor immune cells, declines with age and in conditions of vitamin B12 deficiency, which are the two most well-established conditions that lead to increased systemic levels of MMA. Thus, we hypothesized that increased circulatory levels of MMA would lead to a suppression of CD8+T cell immunity. Treatment of primary CD8+T cells with MMA induced a dysfunctional phenotype characterized by robust immunosuppressive transcriptional reprogramming and marked increases in the expression of the exhaustion regulator, TOX. Accordingly, MMA treatment upregulated exhaustion markers in CD8+T cells and decreased their effector functions, which drove the suppression of anti-tumor immunity in vitro and in vivo. Mechanistically, MMA-induced CD8+T cell exhaustion was associated with a suppression of NADH-regenerating reactions in the TCA cycle and concomitant defects in mitochondrial function. Thus, MMA has immunomodulatory roles, thereby highlighting MMA as an important link between aging, immune dysfunction, and cancer.

Published
2024
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12. TCR-Independent Metabolic Reprogramming Precedes Lymphoma-Driven Changes in T-cell Fate

Author

Hesterberg, Rebecca S., primary, Liu, Min, additional, Elmarsafawi, Aya G., additional, Koomen, John M., additional, Welsh, Eric A., additional, Hesterberg, Stephen G., additional, Ranatunga, Sujeewa, additional, Yang, Chunying, additional, Li, Weimin, additional, Lawrence, Harshani R., additional, Rodriguez, Paulo C., additional, Berglund, Anders E., additional, and Cleveland, John L., additional

Published
2022
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14. Circulating Immunosuppressive Regulatory T Cells Predict Risk of Incident Cutaneous Squamous Cell Carcinoma

Author

Rollison, Dana E., primary, Messina, Jane L., additional, Cherpelis, Basil S., additional, Fenske, Neil A., additional, Schell, Michael J., additional, Adeegbe, Dennis O., additional, Zhao, Yayi, additional, Amorrortu, Rossybelle P., additional, Akuffo, Afua A., additional, Hesterberg, Rebecca S., additional, and Epling-Burnette, Pearlie K., additional

Published
2021
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15. CAR-T Phenotype and Efficacy Is Impaired By Lymphoma-Associated CD39 + T Cells

Author

Jain, Michael D., Yu, Xiaoqing, Atkins, Reginald, Turner, Joel G., Noble, Jerald, Menges, Meghan, Reid, Kayla, Corallo, Salvatore, Cen, Ling, Yoder, Sean J., Abraham Miranda, Julieta, Naderinezhad, Samira, Liu, Hien, Shah, Bijal D., Chavez, Julio C, Dean, Erin, Fahrmann, Johannes, Saini, Neeraj Y., Hanash, Samir, Hesterberg, Rebecca S., Rodriguez, Paulo C., Cleveland, John L., Davila, Marco, Wang, Xuefeng, and Locke, Frederick L.

Published
2023
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16. T Regulatory Cell Subpopulations Associated with Recent Ultraviolet Radiation Exposure in a Skin Cancer Screening Cohort

Author

Hesterberg, Rebecca S., primary, Amorrortu, Rossybelle P., additional, Zhao, Yayi, additional, Hampras, Shalaka, additional, Akuffo, Afua A., additional, Fenske, Neil, additional, Cherpelis, Basil, additional, Balliu, Juliana, additional, Vijayan, Laxmi, additional, Epling-Burnette, Pearlie K., additional, and Rollison, Dana E., additional

Published
2018
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17. Intracellular protein degradation of BRD4 by dBET1 reveals conserved in vivo cereblon function in human and mouse T-cells

Author

Akuffo, Afua Adutwumwa, primary, Alontaga, Aileen, additional, Metclaf, Rainer, additional, Beatty, Matthew S, additional, McDaniel, Jessica, additional, Gunawan, Steven, additional, Ayaz, Muhammad, additional, Becker, Andreas, additional, Hesterberg, Rebecca S, additional, Goodheart, William E, additional, Yang, Yan, additional, Daniel, Kenyon G, additional, Schonbrunn, Ernst, additional, Guida, Wayne, additional, Lawrence, Harshani, additional, Lawrence, Nicholas, additional, and Epling-Burnette, Pearlie, additional

Published
2017
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19. Cereblon harnesses Myc-dependent bioenergetics and activity of CD8+T lymphocytes

Author

Hesterberg, Rebecca S., Beatty, Matthew S., Han, Ying, Fernandez, Mario R., Akuffo, Afua A., Goodheart, William E., Yang, Chunying, Chang, Shiun, Colin, Christelle M., Alontaga, Aileen Y., McDaniel, Jessica M., Mailloux, Adam W., Billington, Julia M.R., Yue, Lanzhu, Russell, Shonagh, Gillies, Robert J., Yun, Sang Y., Ayaz, Muhammad, Lawrence, Nicholas J., Lawrence, Harshani R., Yu, Xue-Zhong, Fu, Jianing, Darville, Lancia N., Koomen, John M., Ren, Xiubao, Messina, Jane, Jiang, Kun, Garrett, Timothy J., Rajadhyaksha, Anjali M., Cleveland, John L., and Epling-Burnette, Pearlie K.

Abstract

Immunomodulatory drugs, such as thalidomide and related compounds, potentiate T-cell effector functions. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex, is the only molecular target for this drug class, where drug-induced, ubiquitin-dependent degradation of known “neosubstrates,” such as IKAROS, AIOLOS, and CK1α, accounts for their biological activity. Far less clear is whether these CRBN E3 ligase-modulating compounds disrupt the endogenous functions of CRBN. We report that CRBN functions in a feedback loop that harnesses antigen-specific CD8+T-cell effector responses. Specifically, Crbndeficiency in murine CD8+T cells augments their central metabolism manifested as elevated bioenergetics, with supraphysiological levels of polyamines, secondary to enhanced glucose and amino acid transport, and with increased expression of metabolic enzymes, including the polyamine biosynthetic enzyme ornithine decarboxylase. Treatment with CRBN-modulating compounds similarly augments central metabolism of human CD8+T cells. Notably, the metabolic control of CD8+T cells by modulating compounds or Crbndeficiency is linked to increased and sustained expression of the master metabolic regulator MYC. Finally, Crbn-deficient T cells have augmented antigen-specific cytolytic activity vs melanoma tumor cells, ex vivo and in vivo, and drive accelerated and highly aggressive graft-versus-host disease. Therefore, CRBN functions to harness the activation of CD8+T cells, and this phenotype can be exploited by treatment with drugs.

Published
2020
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20. Role of Polyamines in Immune Cell Functions.

Author

Hesterberg, Rebecca S., Cleveland, John L., and Epling-Burnette, Pearlie K.

Subjects
POLYAMINES, CELL physiology, IMMUNE response, GLUTAMINE metabolism, KREBS cycle, TUMOR microenvironment, THERAPEUTICS
Abstract

The immune system is remarkably responsive to a myriad of invading microorganisms and provides continuous surveillance against tissue damage and developing tumor cells. To achieve these diverse functions, multiple soluble and cellular components must react in an orchestrated cascade of events to control the specificity, magnitude and persistence of the immune response. Numerous catabolic and anabolic processes are involved in this process, and prominent roles for L-arginine and L-glutamine catabolism have been described, as these amino acids serve as precursors of nitric oxide, creatine, agmatine, tricarboxylic acid cycle intermediates, nucleotides and other amino acids, as well as for ornithine, which is used to synthesize putrescine and the polyamines spermidine and spermine. Polyamines have several purported roles and high levels of polyamines are manifest in tumor cells as well in autoreactive B- and T-cells in autoimmune diseases. In the tumor microenvironment, L-arginine catabolism by both tumor cells and suppressive myeloid cells is known to dampen cytotoxic T-cell functions suggesting there might be links between polyamines and T-cell suppression. Here, we review studies suggesting roles of polyamines in normal immune cell function and highlight their connections to autoimmunity and anti-tumor immune cell function. [ABSTRACT FROM AUTHOR]

Published
2018
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21. CAR-T Phenotype and Efficacy Is Impaired By Lymphoma-Associated CD39 +T Cells

Author

Jain, Michael D., Yu, Xiaoqing, Atkins, Reginald, Turner, Joel G., Noble, Jerald, Menges, Meghan, Reid, Kayla, Corallo, Salvatore, Cen, Ling, Yoder, Sean J., Abraham Miranda, Julieta, Naderinezhad, Samira, Liu, Hien, Shah, Bijal D., Chavez, Julio C, Dean, Erin, Fahrmann, Johannes, Saini, Neeraj Y., Hanash, Samir, Hesterberg, Rebecca S., Rodriguez, Paulo C., Cleveland, John L., Davila, Marco, Wang, Xuefeng, and Locke, Frederick L.

Abstract

Background:Autologous chimeric antigen receptor (CAR) T-cell therapy is standard of care for patients with relapsed or refractory Large B cell Lymphoma (R/R LBCL). Each patient's CAR T product is unique, and the patient-specific determinants of CAR T-cell quality are poorly understood. CD39 is an ectonucleosidase that participates in the conversion of ATP and ADP and is upregulated in cancer. On T-cells, CD39 is expressed on CD4+ Tregs and on exhausted CD8+ T-cells that are prone to apoptosis.

Published
2023
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