26 results on '"Nguyen-Lefebvre AT"'
Search Results
2. OrganEx: A Promising Solution for Rescuing Organs After Prolonged Ischemia
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Anh Thu Nguyen-Lefebvre and Mamatha Bhat
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Hepatology ,Gastroenterology - Published
- 2023
3. Hotspot Immune Exhaustion: Key to Liver Transplant Rejection.
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Nguyen-Lefebvre, Anh Thu and Bhat, Mamatha
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- 2024
- Full Text
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4. Sugar defeats the Hippo: Glycogen regulation of the Hippo pathway in liver
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Jeffrey L. Wrana, Mamatha Bhat, and Anh Thu Nguyen-Lefebvre
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body regions ,Hippo signaling pathway ,chemistry.chemical_compound ,Glycogen ,chemistry ,fungi ,Cell Biology ,Biology ,Molecular Biology ,Cell biology - Abstract
Liver glycogen is famous for glucose storage, but new work by Liu et al. (2021) now reveals that it's been hiding a few secrets and can directly promote liver enlargement and tumorigenesis by sequestering the tumor-suppressive Hippo signaling pathway.
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- 2021
5. Identification of human, rat and chicken ribosomal proteins by a combination of two-dimensional polyacrylamide gel electrophoresis and mass spectrometry
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Nguyen-Lefebvre, Anh Thu, Gonin-Giraud, Sandrine, Scherl, Alexander, Arboit, Patrizia, Granger, Laure, Sanchez, Jean-Charles, Diaz, Jean-Jacques, Gandrillon, Olivier, and Madjar, Jean-Jacques
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- 2011
- Full Text
- View/download PDF
6. Sugar defeats the Hippo: Glycogen regulation of the Hippo pathway in liver
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Nguyen-Lefebvre, Anh Thu, primary, Bhat, Mamatha, additional, and Wrana, Jeffrey L., additional
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- 2021
- Full Text
- View/download PDF
7. V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors
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Nguyen-Lefebvre, A T, Leprun, G, Morin, V, Viñuelas, J, Couté, Y, Madjar, J-J, Gandrillon, O, and Gonin-Giraud, S
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- 2014
- Full Text
- View/download PDF
8. HLA‐G dimer targets Granzyme B pathway to prolong human renal allograft survival
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Daniel D. Horuzsko, Christine Callaway, Anh Thu Nguyen-Lefebvre, Rajan Kapoor, Vera Portik-Dobos, Ashwin Ajith, Anatolij Horuzsko, Carlos Zayas, Laura L. Mulloy, and Katsumi Maenaka
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Adult ,Graft Rejection ,0301 basic medicine ,T-Lymphocytes ,Dimer ,Fetal tissue ,Human leukocyte antigen ,CD8-Positive T-Lymphocytes ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Granzymes ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Leukocyte Immunoglobulin-like Receptor B1 ,0302 clinical medicine ,Antigens, CD ,HLA-G ,Concanavalin A ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,HLA-G Antigens ,Pregnancy ,business.industry ,Research ,Graft Survival ,Flow Cytometry ,medicine.disease ,Kidney Transplantation ,Granzyme B ,030104 developmental biology ,chemistry ,Immunology ,Humanized mouse ,Renal allograft ,Female ,business ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Human leukocyte antigen G (HLA-G), a nonclassic HLA class Ib molecule involved in the maintenance of maternal tolerance to semiallogeneic fetal tissues during pregnancy, has emerged as a potential therapeutic target to control allograft rejection. We demonstrate here that the level of soluble HLA-G dimer was higher in a group of 90 patients with a functioning renal allograft compared with 40 patients who rejected (RJ) their transplants. The HLA-G dimer level was not affected by demographic status. One of the potential mechanisms in tissue-organ allograft rejection involves the induction of granzymes and perforin, which are the main effector molecules expressed by CD8(+) cytotoxic T lymphocytes and function to destroy allogeneic transplants. Using genomics and molecular and cellular analyses of cells from T-cell–mediated RJ and nonrejected kidney transplant patients, cells from leukocyte Ig-like receptor B1 (LILRB1) transgenic mice, humanized mice, and genetically engineered HLA-G dimer, we demonstrated a novel mechanism by which HLA-G dimer inhibits activation and cytotoxic capabilities of human CD8(+) T cells. This mechanism implicated the down-regulation of Granzyme B expression and the essential involvement of LILRB1. Thus, HLA-G dimer has the potential to be a specific and effective therapy for prevention of allograft rejection and prolongation of graft survival.—Ajith, A., Portik-Dobos, V., Nguyen-Lefebvre, A. T., Callaway, C., Horuzsko, D. D., Kapoor, R., Zayas, C., Maenaka, K., Mulloy, L. L., Horuzsko, A. HLA-G dimer targets Granzyme B pathway to prolong human renal allograft survival.
- Published
- 2019
9. The hippo pathway: A master regulator of liver metabolism, regeneration, and disease
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Jeffrey L. Wrana, Nazia Selzner, Anh Thu Nguyen-Lefebvre, and Mamatha Bhat
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0301 basic medicine ,Cell ,Protein Serine-Threonine Kinases ,Biology ,Biochemistry ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Genetics ,medicine ,Animals ,Humans ,Hippo Signaling Pathway ,Molecular Biology ,Hippo signaling pathway ,Liver Diseases ,Regeneration (biology) ,medicine.disease ,Liver regeneration ,Liver Regeneration ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Liver ,Stem cell ,Liver cancer ,030217 neurology & neurosurgery ,Homeostasis ,Biotechnology - Abstract
The liver is the only visceral organ in the body with a tremendous capacity to regenerate in response to insults that induce inflammation, cell death, and injury. Liver regeneration is a complicated process involving a well-orchestrated activation of non-parenchymal cells in the injured area and proliferation of undamaged hepatocytes. Furthermore, the liver has a Hepatostat, defined as adjustment of its volume to that required for homeostasis. Understanding the mechanisms that control different steps of liver regeneration is critical to informing therapies for liver repair, to help patients with liver disease. The Hippo signaling pathway is well known for playing an essential role in the control and regulation of liver size, regeneration, stem cell self-renewal, and liver cancer. Thus, the Hippo pathway regulates dynamic cell fates in liver, and in absence of its downstream effectors YAP and TAZ, liver regeneration is severely impaired, and the proliferative expansion of liver cells blocked. We will mainly review upstream mechanisms activating the Hippo signaling pathway following partial hepatectomy in mouse model and patients, its roles during different steps of liver regeneration, metabolism, and cancer. We will also discuss how targeting the Hippo signaling cascade might improve liver regeneration and suppress liver tumorigenesis.
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- 2021
10. The hippo pathway: A master regulator of liver metabolism, regeneration, and disease
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Nguyen‐Lefebvre, Anh Thu, primary, Selzner, Nazia, additional, Wrana, Jeffrey L., additional, and Bhat, Mamatha, additional
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- 2021
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11. The innate immune receptor TREM-1 promotes liver injury and fibrosis
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Ali S. Arbab, Anatolij Horuzsko, Daniel D. Horuzsko, Vera Portik-Dobos, Ashwin Ajith, Amiran Dzutsev, Anh Thu Nguyen-Lefebvre, Giorgio Trinchieri, and Ramses F. Sadek
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Liver Cirrhosis ,Male ,0301 basic medicine ,Kupffer Cells ,Inflammation ,Monocytes ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,Liver disease ,Fibrosis ,medicine ,Animals ,Humans ,Liver injury ,business.industry ,Kupffer cell ,General Medicine ,medicine.disease ,Mice, Mutant Strains ,Triggering Receptor Expressed on Myeloid Cells-1 ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Liver ,Chronic Disease ,Cancer research ,Hepatic stellate cell ,Cytokines ,Female ,medicine.symptom ,business ,Hepatic fibrosis ,Research Article - Abstract
Inflammation occurs in all tissues in response to injury or stress and is the key process underlying hepatic fibrogenesis. Targeting chronic and uncontrolled inflammation is one strategy to prevent liver injury and fibrosis progression. Here, we demonstrate that triggering receptor expressed on myeloid cells 1 (TREM-1), an amplifier of inflammation, promotes liver disease by intensifying hepatic inflammation and fibrosis. In the liver, TREM-1 expression was limited to liver macrophages and monocytes and was highly upregulated on Kupffer cells, circulating monocytes, and monocyte-derived macrophages in a mouse model of chronic liver injury and fibrosis induced by carbon tetrachloride (CCl4) administration. TREM-1 signaling promoted proinflammatory cytokine production and mobilization of inflammatory cells to the site of injury. Deletion of Trem1 reduced liver injury, inflammatory cell infiltration, and fibrogenesis. Reconstitution of Trem1-deficient mice with Trem1-sufficient Kupffer cells restored the recruitment of inflammatory monocytes and the severity of liver injury. Markedly increased infiltration of liver fibrotic areas with TREM-1–positive Kupffer cells and monocytes/macrophages was found in patients with hepatic fibrosis. Our data support a role of TREM-1 in liver injury and hepatic fibrogenesis and suggest that TREM-1 is a master regulator of Kupffer cell activation, which escalates chronic liver inflammatory responses, activates hepatic stellate cells, and reveals a mechanism of promotion of liver fibrosis.
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- 2018
12. SALL1 expression in acute myeloid leukemia
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Xiao Shuai, Mingqiang Ren, Wei Hou, Banabihari Giri, Michael Rauchman, Huda S Salman, Hasan Korkaya, Lynn Robbins, Anh Thu Nguyen-Lefebvre, and Yupo Ma
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0301 basic medicine ,medicine.medical_specialty ,Hematology ,business.industry ,SALL1 ,CD34 ,Myeloid leukemia ,medicine.disease ,Minimal residual disease ,03 medical and health sciences ,Haematopoiesis ,Leukemia ,030104 developmental biology ,0302 clinical medicine ,Oncology ,AML ,030220 oncology & carcinogenesis ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Cancer research ,Progenitor cell ,Stem cell ,business ,Research Paper - Abstract
// Huda Salman 1, 2 , Xiao Shuai 2, 3, * , Anh Thu Nguyen-Lefebvre 1, * , Banabihari Giri 1 , Mingqiang Ren 1 , Michael Rauchman 4 , Lynn Robbins 4 , Wei Hou 2 , Hasan Korkaya 1 and Yupo Ma 2 1 Georgia Regent University Cancer Center, Augusta, GA, USA 2 Present address: Stony Brook University Cancer Center, Stony Brook, NY, USA 3 Department of Hematology, West China hospital of Sichuan University, Chengdu, P.R. China 4 Department of Nephrology, Saint Louis University, St Louis, MO, USA * These authors contributed equally to this work Correspondence to: Huda Salman, email: huda.salman@stonybrookmedicine.edu Keywords: SALL1; AML Received: August 18, 2017 Accepted: October 25, 2017 Published: December 15, 2017 ABSTRACT Similar signaling pathways could operate in both normal hematopoietic stem and progenitor cells (HSPCs) and leukemia stem cells (LSCs). Thus, targeting LSCs signaling without substantial toxicities to normal HSPCs remains challenging. SALL1, is a member of the transcriptional network that regulates stem cell pluripotency, and lacks significant expression in most adult tissues, including normal bone marrow (NBM). We examined the expression and functional characterization of SALL1 in NBM and in acute myeloid leukemia (AML) using in vitro and in vivo assays. We showed that SALL1 is expressed preferentially in LSCs- enriched CD34+CD38- cell subpopulation but not in NBM. SALL1 inhibition resulted in decreased cellular proliferation and in inferior AML engraftment in NSG mice and it was also associated with upregulation of PTEN and downregulation of m-TOR, β-catenin, and NF- қB expression. These findings suggest that SALL1 inhibition interrupts leukemogenesis. Further studies to validate SALL1 as a potential biomarker for minimal residual disease (MRD) and to determine SALL1’s role in prognostication are ongoing. Additionally, pre-clinical evaluation of SALL1 as a therapeutic target in AML is warranted.
- Published
- 2017
13. OrganEx: A Promising Solution for Rescuing Organs After Prolonged Ischemia
- Author
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Nguyen-Lefebvre, Anh Thu and Bhat, Mamatha
- Published
- 2023
- Full Text
- View/download PDF
14. HLA‐G dimer targets Granzyme B pathway to prolong human renal allograft survival
- Author
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Ajith, Ashwin, primary, Portik‐Dobos, Vera, additional, Nguyen‐Lefebvre, Anh Thu, additional, Callaway, Christine, additional, Horuzsko, Daniel D., additional, Kapoor, Rajan, additional, Zayas, Carlos, additional, Maenaka, Katsumi, additional, Mulloy, Laura L., additional, and Horuzsko, Anatolij, additional
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- 2019
- Full Text
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15. The innate immune receptor TREM-1 promotes liver injury and fibrosis.
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Anh Thu Nguyen-Lefebvre, Ajith, Ashwin, Portik-Dobos, Vera, Horuzsko, Daniel David, Arbab, Ali Syed, Dzutsev, Amiran, Sadek, Ramses, Trinchieri, Giorgio, Horuzsko, Anatolij, and Nguyen-Lefebvre, Anh Thu
- Subjects
- *
NATURAL immunity , *FIBROSIS , *LIVER injuries , *DISEASE progression , *GENE expression - Abstract
Inflammation occurs in all tissues in response to injury or stress and is the key process underlying hepatic fibrogenesis. Targeting chronic and uncontrolled inflammation is one strategy to prevent liver injury and fibrosis progression. Here, we demonstrate that triggering receptor expressed on myeloid cells 1 (TREM-1), an amplifier of inflammation, promotes liver disease by intensifying hepatic inflammation and fibrosis. In the liver, TREM-1 expression was limited to liver macrophages and monocytes and was highly upregulated on Kupffer cells, circulating monocytes, and monocyte-derived macrophages in a mouse model of chronic liver injury and fibrosis induced by carbon tetrachloride (CCl4) administration. TREM-1 signaling promoted proinflammatory cytokine production and mobilization of inflammatory cells to the site of injury. Deletion of Trem1 reduced liver injury, inflammatory cell infiltration, and fibrogenesis. Reconstitution of Trem1-deficient mice with Trem1-sufficient Kupffer cells restored the recruitment of inflammatory monocytes and the severity of liver injury. Markedly increased infiltration of liver fibrotic areas with TREM-1-positive Kupffer cells and monocytes/macrophages was found in patients with hepatic fibrosis. Our data support a role of TREM-1 in liver injury and hepatic fibrogenesis and suggest that TREM-1 is a master regulator of Kupffer cell activation, which escalates chronic liver inflammatory responses, activates hepatic stellate cells, and reveals a mechanism of promotion of liver fibrosis. [ABSTRACT FROM AUTHOR]
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- 2018
- Full Text
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16. The innate immune receptor TREM-1 promotes liver injury and fibrosis
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Nguyen-Lefebvre, Anh Thu, primary, Ajith, Ashwin, additional, Portik-Dobos, Vera, additional, Horuzsko, Daniel David, additional, Arbab, Ali Syed, additional, Dzutsev, Amiran, additional, Sadek, Ramses, additional, Trinchieri, Giorgio, additional, and Horuzsko, Anatolij, additional
- Published
- 2018
- Full Text
- View/download PDF
17. SALL1expression in acute myeloid leukemia
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Salman, Huda, primary, Shuai, Xiao, additional, Nguyen-Lefebvre, Anh Thu, additional, Giri, Banabihari, additional, Ren, Mingqiang, additional, Rauchman, Michael, additional, Robbins, Lynn, additional, Hou, Wei, additional, Korkaya, Hasan, additional, and Ma, Yupo, additional
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- 2017
- Full Text
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18. V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors
- Author
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Valérie Morin, Sandrine Gonin-Giraud, Anh Thu Nguyen-Lefebvre, Yohann Couté, Olivier Gandrillon, Jean Jacques Madjar, José Viñuelas, G. Leprun, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Etude de la dynamique des protéomes (EDyP ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'étude de la dynamique des protéomes (LEDyP), and Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Ribosomal Proteins ,Cancer Research ,Erythrocytes ,animal structures ,Transcription, Genetic ,Immunoprecipitation ,[SDV]Life Sciences [q-bio] ,Biology ,Ribosome ,Transcriptome ,Ribosomal protein ,Polysome ,Genetics ,Animals ,Humans ,HSP70 Heat-Shock Proteins ,RNA, Messenger ,Serial analysis of gene expression ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,Stem Cells ,Oncogene Proteins v-erbA ,Cell Transformation, Viral ,Molecular biology ,Hsp70 ,Cell biology ,Protein Biosynthesis ,Eukaryotic Ribosome ,Chickens ,Ribosomes - Abstract
The v-erbA oncogene transforms chicken erythrocytic progenitors (T2EC) by blocking their differentiation and freezing them in a state of self-renewal. Transcriptomes of T2EC, expressing either v-erbA or a non-transforming form of v-erbA (S61G), were compared using serial analysis of gene expression and some, but not all, mRNA-encoding ribosomal proteins were seen to be affected by v-erbA. These results suggest that this oncogene could modulate the composition of ribosomes. In the present study, we demonstrate, using two-dimensional difference in gel electrophoresis, that v-erbA-expressing cells have a lower amount of RPL11 associated with the ribosomes. The presence of ribosomes devoid of RPL11 in v-erbA-expressing cells was further confirmed by immunoprecipitation. In order to assess the possible impact of these specialized ribosomes on the translational activity, we analyzed proteomes of either v-erbA or S61G-expressing cells using 2D/mass spectrometry, and identified nine proteins present in differing amounts within these cells. Among these proteins, we focused on HSP70 because of its involvement in erythroid differentiation. Our results indicate that, in v-erbA-expressing cells, hsp70 is not only transcribed but also translated more efficiently, as shown by polyribosome fractionation experiments. We demonstrate here, for the first time, the existence of ribosomes with different protein components, notably ribosomes devoid of RPL11, and a regulation of mRNA translation depending on v-erbA oncogene expression.
- Published
- 2013
19. Mouse models for studies of HLA-G functions in basic science and pre-clinical research
- Author
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Vera Portik-Dobos, Anh Thu Nguyen-Lefebvre, Daniel D. Horuzsko, Anatolij Horuzsko, Laura L. Mulloy, and Ashwin Ajith
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0301 basic medicine ,Graft Rejection ,Immunology ,Mice, Transgenic ,Human leukocyte antigen ,Mice, SCID ,Biology ,Bioinformatics ,Infections ,Immune tolerance ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Pregnancy ,HLA-G ,Neoplasms ,Immune Tolerance ,Immunology and Allergy ,Animals ,Humans ,Precision Medicine ,Receptor ,HLA-G Antigens ,General Medicine ,Organ Transplantation ,Transplantation ,030104 developmental biology ,Tumor Escape ,Humanized mouse ,Models, Animal ,Female ,Immunotherapy ,030215 immunology - Abstract
HLA-G was described originally as a tolerogenic molecule that allows the semiallogeneic fetus to escape from recognition by the maternal immune response. This review will discuss different steps in the study of HLA-G expression and functions in vivo, starting with analyses of expression of the HLA-G gene and its receptors in transgenic mice, and continuing with applications of HLA-G and its receptors in prevention of allograft rejection, transplantation tolerance, and controlling the development of infection. Humanized mouse models have been discussed for developing in vivo studies of HLA-G in physiological and pathological conditions. Collectively, animal models provide an opportunity to evaluate the importance of the interaction between HLA-G and its receptors in terms of its ability to regulate immune responses during maternal-fetal tolerance, survival of allografts, tumor-escape mechanisms, and development of infections when both HLA-G and its receptors are expressed. In addition, in vivo studies on HLA-G also offer novel approaches to achieve a reproducible transplantation tolerance and to develop personalized medicine to prevent allograft rejection.
- Published
- 2015
20. Kupffer Cell Metabolism and Function
- Author
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Nguyen-Lefebvre, Anh Thu and Horuzsko, Anatolij
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Article - Abstract
Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions.
- Published
- 2015
21. Mouse models for studies of HLA-G functions in basic science and pre-clinical research
- Author
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Nguyen-Lefebvre, Anh Thu, primary, Ajith, Ashwin, additional, Portik-Dobos, Vera, additional, Horuzsko, Daniel D., additional, Mulloy, Laura L., additional, and Horuzsko, Anatolij, additional
- Published
- 2016
- Full Text
- View/download PDF
22. Implication of ribosomal proteins in transformation process induced by v-erbA oncogene
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Nguyen-Lefebvre, Anh Thu and STAR, ABES
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Two-Dimensional Difference Gel Electrophoresis ,Progéniteurs érythrocytaires aviaires ,RPL11 ,Ribosomal composition ,Two- Dimensional Difference Gel Electrophoresis ,Composition des ribosomes ,Oncogène v-erbA ,Ribosomal proteins ,Chicken erythrocytic progenitors ,Protéines ribosomiques ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,V-erbA oncogene - Abstract
The v-erbA oncogene transforms chicken erythroid progenitors by blocking their differentiation andpreventing them to exit a state of self-renewal. The transcriptome of primary avian erythroidprogenitors cells (T2EC) expressing either v-erbA or a non-transforming form of v-erbA werecompared by SAGE. Only some, but not all, mRNAs encoding ribosomal proteins were shown to beaffected. These results suggest that v-erbA could modulate the composition of ribosomes and/ormodulate the extraribosomal functions of specific ribosomal proteins. We therefore decided to analyzethe level of ribosomal proteins associated to ribosomes by 2D-DIGE performed on purified ribosomes.A statistical analysis performed on 4 independent flip-flop experiments demonstrated that the level ofRPL11 is significantly lower in T2EC expressing v-erbA as compared to the non-transforming form ofv-erbA. These data suggest the presence of ribosomes without RPL11 in T2EC expressing v-ErbA.Results obtained from immunoprecipitation experiments were strengthened this hypothesis. The set ofthese data evoke the involvement of ribosomal proteins, and specially RPL11, in the v-erbAtransformation process both at the translational level and possibly in its extra-ribosomal function.Overexpression of RPL11 in T2EC showed a decrease of cell proliferation., L’oncogène v-erbA transforme les progéniteurs érythrocytaires primaires aviaires (T2EC) en bloquantleur engagement d’un programme d’auto-renouvellement vers un programme de différenciation. Unecomparaison trancriptomique de T2EC exprimant soit v-erbA, soit une forme non transformante de verbAa été réalisée par SAGE et RT-qPCR. Seuls quelques uns, mais pas tous les messagers codant lesprotéines ribosomiques sont réprimés. Ces résultats suggèrent que v-erbA pourrait moduler lacomposition des ribosomes et/ou moduler les fonctions extra-ribosomiques de protéines ribosomiquesspécifiques. Ainsi, nous avons décidé d’analyser le taux des protéines ribosomiques associées auxribosomes par 2D-DIGE à partir des ribosomes purifiés. L’analyse statistique effectuée sur 4expériences indépendantes avec des marquages inversées a montré de manière significative que letaux de RPL11 est inférieur dans les T2EC exprimant v-erbA comparé à ceux exprimant la forme nontransformante de v-erbA. Ces données indiquent l’existence de ribosomes dépourvus de RPL11 dansles T2EC sous l’effet de v-erbA. Les résultats des expériences d’immunoprécipitation ont conforté cettehypothèse. L’ensemble des résultats obtenus suggèrent l’implication des protéines ribosomiques, etspécialement celle de RPL11, dans les processus de transformation induite par l’oncogène v-erbA, à lafois au niveau de la traduction, et probablement par sa fonction extra-ribosomique. L’analyse de lafonction biologique de RPL11 a montré qu’une sur-expression de RPL11 dans les T2EC retarderait laprolifération cellulaire.
- Published
- 2012
23. Identification of human, rat and chicken ribosomal proteins by a combination of two-dimensional polyacrylamide gel electrophoresis and mass spectrometry
- Author
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Laure Granger, Olivier Gandrillon, Anh Thu Nguyen-Lefebvre, Alexander Scherl, Patrizia Arboit, Jean-Charles Sanchez, Jean Jacques Madjar, Jean-Jacques Diaz, Sandrine Gonin-Giraud, Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biomedical Proteomics Research Group (BPRG), Centre médical universitaire, Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)
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Ribosomal Proteins ,Electrophoresis, Gel, Two-Dimensional/methods ,Databases, Factual ,Biophysics ,Biology ,Trypsin/metabolism ,Tandem mass spectrometry ,Tandem mass tag ,Mass spectrometry ,Tandem Mass Spectrometry/methods ,Biochemistry ,03 medical and health sciences ,Ribosomal protein ,Tandem Mass Spectrometry ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Electrophoresis, Gel, Two-Dimensional ,Trypsin ,ddc:576 ,Polyacrylamide gel electrophoresis ,030304 developmental biology ,Gel electrophoresis ,0303 health sciences ,Chromatography ,Molecular mass ,030302 biochemistry & molecular biology ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Rats ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Ribosomal Proteins/analysis/chemistry/metabolism ,Chickens ,medicine.drug ,HeLa Cells - Abstract
International audience; To identify the exact spot position of human, rat and chicken ribosomal proteins (RP) separated by two-dimensional polyacrylamide gel electrophoresis (2-DE), a 2-DE system was designed to separate RP with a pI>8.6 according to their charge in the first dimension and to their molecular mass in the second dimension. Individual proteins were excised from the gels and identified by mass spectrometry after digestion by trypsin. In addition, a mixture of purified RP from these three species was also analyzed by tandem mass tag spectrometry. By combining those two methods 74 RP from human, 76 from rat and 67 from chicken were identified according to the nomenclature initially defined for rat liver RP and by using the Swiss-Prot/trEMBL databases. Whereas human and rat RP were well described, most of RP from chicken were not characterized in databases, since 35 out of 67 chicken RP identified in this study were not listed yet. We propose here the first comprehensive description of chicken RP and their comparison to those from human and rat.
- Published
- 2010
24. V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors
- Author
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Nguyen-Lefebvre, A T, primary, Leprun, G, additional, Morin, V, additional, Viñuelas, J, additional, Couté, Y, additional, Madjar, J-J, additional, Gandrillon, O, additional, and Gonin-Giraud, S, additional
- Published
- 2013
- Full Text
- View/download PDF
25. SALL1 expression in acute myeloid leukemia.
- Author
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Salman H, Shuai X, Nguyen-Lefebvre AT, Giri B, Ren M, Rauchman M, Robbins L, Hou W, Korkaya H, and Ma Y
- Abstract
Similar signaling pathways could operate in both normal hematopoietic stem and progenitor cells (HSPCs) and leukemia stem cells (LSCs). Thus, targeting LSCs signaling without substantial toxicities to normal HSPCs remains challenging. SALL1, is a member of the transcriptional network that regulates stem cell pluripotency, and lacks significant expression in most adult tissues, including normal bone marrow (NBM). We examined the expression and functional characterization of SALL1 in NBM and in acute myeloid leukemia (AML) using in vitro and in vivo assays. We showed that SALL1 is expressed preferentially in LSCs- enriched CD34+CD38- cell subpopulation but not in NBM. SALL1 inhibition resulted in decreased cellular proliferation and in inferior AML engraftment in NSG mice and it was also associated with upregulation of PTEN and downregulation of m-TOR, β-catenin, and NF-қB expression. These findings suggest that SALL1 inhibition interrupts leukemogenesis. Further studies to validate SALL1 as a potential biomarker for minimal residual disease (MRD) and to determine SALL1's role in prognostication are ongoing. Additionally, pre-clinical evaluation of SALL1 as a therapeutic target in AML is warranted., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.
- Published
- 2017
- Full Text
- View/download PDF
26. Kupffer Cell Metabolism and Function.
- Author
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Nguyen-Lefebvre AT and Horuzsko A
- Abstract
Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions.
- Published
- 2015
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