Benoit Viollet

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (271)1852.76 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: An increase in muscle tissue delivery of glucose and insulin due to insulin-induced vasodilatation of arterioles and the subsequent increase in muscle microvascular perfusion is known to be a requisite response to food intake. An impairment of this physiological response could play a role in the development of both hyperglycemia and hypertension.
    11/2015; 11(4):183-184. DOI:10.1007/s12467-013-0137-0
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    ABSTRACT: AMPK is a master regulator of cellular metabolism that exerts either oncogenic or tumor suppressor activity depending on context. Here, we report that the specific AMPK agonist GSK621 selectively kills acute myeloid leukemia (AML) cells but spares normal hematopoietic progenitors. This differential sensitivity results from a unique synthetic lethal interaction involving concurrent activation of AMPK and mTORC1. Strikingly, the lethality of GSK621 in primary AML cells and AML cell lines is abrogated by chemical or genetic ablation of mTORC1 signaling. The same synthetic lethality between AMPK and mTORC1 activation is established in CD34-positive hematopoietic progenitors by constitutive activation of AKT or enhanced in AML cells by deletion of TSC2. Finally, cytotoxicity in AML cells from GSK621 involves the eIF2α/ATF4 signaling pathway that specifically results from mTORC1 activation. AMPK activation may represent a therapeutic opportunity in mTORC1-overactivated cancers.
    Cell Reports 06/2015; 11(9):1446. DOI:10.1016/j.celrep.2015.04.063 · 7.21 Impact Factor
  • Marc Foretz, Benoit Viollet
    Nature Reviews Endocrinology 06/2015; DOI:10.1038/nrendo.2015.85 · 12.96 Impact Factor
  • David Carling, Benoit Viollet
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    ABSTRACT: The recent exciting advances in our understanding of the regulation of the energy sensor AMP-activated protein kinase (AMPK), together with renewed appreciation of its importance in maintaining cellular function, brought together leading scientists at a recent FASEB-sponsored meeting in September 2014. Here, we report some of the highlights of this conference. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell metabolism 06/2015; 21(6). DOI:10.1016/j.cmet.2015.05.005 · 16.75 Impact Factor
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    ABSTRACT: Autophagy is induced during differentiation of human monocytes into macrophages that is mediated by CSF1/CSF-1/M-CSF (colony stimulating factor 1 [macrophage]). However, little is known about the molecular mechanisms that link CSF1 receptor engagement to the induction of autophagy. Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation. We reveal that this pathway links P2RY6 to the induction of autophagy, and we decipher the signalling network that links the CSF1 receptor to P2RY6-mediated autophagy and monocyte differentiation. In addition, we show that the physiological P2RY6 ligand UDP and the specific P2RY6 agonist MRS2693 can restore normal monocyte differentiation through reinduction of autophagy in primary myeloid cells from some but not all chronic myelomonocytic leukemia (CMML) patients. Collectively, our findings highlight an essential role for PRKAA1-mediated autophagy during differentiation of human monocytes and pave the way for future therapeutic interventions for CMML.
    Autophagy 06/2015; DOI:10.1080/15548627.2015.1034406 · 11.42 Impact Factor
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    ABSTRACT: Intracellular pathogens are known to manipulate host cell regulatory pathways to establish an optimal environment for their growth and survival. Pathogens employ active mechanisms to hijack host cell metabolism and acquire existing nutrient and energy store. The role of the cellular energy sensor AMP-activated protein kinase (AMPK) in the regulation of cellular energy homeostasis is well documented. Here, we highlight recent advances showing the importance of AMPK signaling in pathogen-host interactions. Pathogens interact with AMPK by a variety of mechanisms aimed at reprogramming host cell metabolism to their own benefit. Stimulation of AMPK activity provides an efficient process to rapidly adapt pathogen metabolism to the major nutritional changes often encountered during the different phases of infection. However, inhibition of AMPK is also used by pathogens to manipulate innate host response, indicating that AMPK appears relevant to restriction of pathogen infection. We also document the effects of pharmacological AMPK modulators on pathogen proliferation and survival. This review illustrates intricate pathogen-AMPK interactions that may be exploited to the development of novel anti-pathogen therapies.
    Current drug targets 04/2015; · 3.60 Impact Factor
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    ABSTRACT: Skeletal muscle possesses a remarkable plasticity and responds to environmental and physiological challenges by changing its phenotype in terms of size, composition, and metabolic properties. Muscle fibers rapidly adapt to drastic changes in energy demands during exercise through fine-tuning of the balance between catabolic and anabolic processes. One major sensor of energy demand in exercising muscle is AMP-activated protein kinase (AMPK). Recent advances have shed new light on the relevance of AMPK both as a multitask gatekeeper and as an energy regulator in skeletal muscle. Here we summarize recent findings on the function of AMPK in skeletal muscle adaptation to contraction and highlight its role in the regulation of energy metabolism and the control of skeletal muscle regeneration post-injury. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Trends in Endocrinology and Metabolism 03/2015; 26(6). DOI:10.1016/j.tem.2015.02.009 · 8.87 Impact Factor
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    ABSTRACT: Cigarette smoking promotes body weight reduction in humans while paradoxically also promoting insulin resistance (IR) and hyperinsulinemia. However, the mechanisms behind these effects are unclear. Here we show that nicotine, a major constituent of cigarette smoke, selectively activates AMP-activated protein kinase α2 (AMPKα2) in adipocytes, which in turn phosphorylates MAP kinase phosphatase-1 (MKP1) at serine 334, initiating its proteasome-dependent degradation. The nicotine-dependent reduction of MKP1 induces the aberrant activation of both p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, leading to increased phosphorylation of insulin receptor substrate 1 (IRS1) at serine 307. Phosphorylation of IRS1 leads to its degradation, protein kinase B inhibition, and the loss of insulin-mediated inhibition of lipolysis. Consequently, nicotine increases lipolysis, which results in body weight reduction, but this increase also elevates the levels of circulating free fatty acids and thus causes IR in insulin-sensitive tissues. These results establish AMPKα2 as an essential mediator of nicotine-induced whole-body IR in spite of reductions in adiposity.
    Nature medicine 03/2015; 21(4). DOI:10.1038/nm.3826 · 28.05 Impact Factor
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    ABSTRACT: Oogenesis and folliculogenesis are dynamic processes that are regulated by endocrine, paracrine and autocrine signals. These signals are exchanged between the oocyte and the somatic cells of the follicle. Here we analyzed the role of AMP-activated protein kinase (AMPK), an important regulator of cellular energy homeostasis, by using transgenic mice deficient in α1AMPK specifically in the oocyte. We found a decrease of 27% in litter size was observed in ZP3-α1AMPK-/- (ZP3-KO) female mice. Following in vitro fertilization, where conditions are stressful for the oocyte and embryo, ZP3-KO oocytes were 68% less likely to pass the 2-cell stage. In vivo and in cumulus-oocyte complexes, several proteins involved in junctional communication, such as connexin37 and N-cadherin were down-regulated in the absence of α1AMPK. While the two signalling pathways (PKA and MAPK) involved in the junctional communication between the cumulus/granulosa cells and the oocyte were stimulated in control oocytes, ZP3-KO oocytes exhibited only low phosphorylation of MAPK or CREB proteins. In addition, MII oocytes deficient in α1AMPK had a 3-fold lower ATP concentration, an increase in abnormal mitochondria, and a decrease in cytochrome C and PGC1α levels, suggesting perturbed energy production by mitochondria. The absence of α1AMPK also induced a reduction in histone deacetylase activity, which was associated with an increase in histone H3 acetylation (K9/K14 residues). Together, the results of the present study suggest that absence of AMPK, modifies oocyte quality through energy processes and oocyte/somatic cell communication. The limited effect observed in vivo could be partly due to a favourable follicle microenvironment where nutrients, growth factors, and adequate cell interaction were present. Whereas in a challenging environment such as that of in vitro culture following IVF, the phenotype is revealed.
    PLoS ONE 03/2015; 10(3):e0119680. DOI:10.1371/journal.pone.0119680 · 3.53 Impact Factor
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    ABSTRACT: Metabolic manipulation of host cells by intracellular pathogens is currently recognized to play an important role in the pathology of infection. Nevertheless, little information is available regarding mitochondrial energy metabolism in Leishmania infected macrophages. Here, we demonstrate that during L. infantum infection, macrophages switch from an early glycolytic metabolism to an oxidative phosphorylation, and this metabolic deviation requires SIRT1 and LKB1/AMPK. SIRT1 or LBK1 deficient macrophages infected with L. infantum failed to activate AMPK and up-regulate its targets such as Slc2a4 and Ppargc1a, which are essential for parasite growth. As a result, impairment of metabolic switch caused by SIRT1 or AMPK deficiency reduces parasite load in vitro and in vivo. Overall, our work demonstrates the importance of SIRT1 and AMPK energetic sensors for parasite intracellular survival and proliferation, highlighting the modulation of these proteins as potential therapeutic targets for the treatment of leishmaniasis.
    PLoS Pathogens 03/2015; 11(3):e1004684. · 8.06 Impact Factor
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    ABSTRACT: Protein synthesis is a major energy-consuming process, which is rapidly repressed upon energy stress by AMPK. How energy deficiency affects translation of mRNAs that cope with the stress response is poorly understood. We found that mitochondrial genes remain translationally active upon energy deprivation. Surprisingly, inhibition of translation is partially retained in AMPKα1/AMPKα2 knockout cells. Mitochondrial mRNAs are enriched with TISU, a translation initiator of short 5' UTR, which confers resistance specifically to energy stress. Purified 48S preinitiation complex is sufficient for initiation via TISU AUG, when preceded by a short 5' UTR. eIF1 stimulates TISU but inhibits non-TISU-directed initiation. Remarkably, eIF4GI shares this activity and also interacts with eIF1. Furthermore, eIF4F is released upon 48S formation on TISU. These findings describe a specialized translation tolerance mechanism enabling continuous translation of TISU genes under energy stress and reveal that a key step in start codon selection of short 5' UTR is eIF4F release. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell Metabolism 03/2015; 21(3):479-92. DOI:10.1016/j.cmet.2015.02.010 · 16.75 Impact Factor
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    ABSTRACT: Author Summary Leishmania infantum, a causative agent of visceral leishmaniasis, is able to infect host macrophages and modulate a myriad of signalling pathways that contributes to the disease outcome. In order to survive, L. infantum must compete with the host for the same metabolic resources, however scarce attention has been dedicated to clarify the potential interference of the parasite with the host metabolic pathways and its impact for the infection outcome. We analysed the macrophage metabolic alterations induced by L. infantum focusing on host energetic players exploited by the parasite. We describe that L. infantum induced a metabolic switch from an early aerobic glycolytic environment to a later mitochondrial metabolism. In this process, L. infantum modulates important energetic sensors of the host, such as the SIRT1-LKB1-AMPK axis. This triad is important for the recovery of the host energetic status and also for the parasite survival. With this work, we demonstrate that the host SIRT1-LKB1-AMPK axis has a crucial impact on the parasite survival in vitro and in vivo.
    PLoS Pathogens 03/2015; 11(3):e1004684. DOI:10.1371/journal.ppat.1004684 · 8.06 Impact Factor
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    ABSTRACT: AMP-activated protein kinase (AMPK) is a key cellular energy sensor and regulator of metabolic homeostasis. Although best known for its effects on carbohydrate and lipid metabolism, AMPK is implicated in diverse cellular processes, including mitochondrial biogenesis, autophagy, and cell growth and proliferation. To further our understanding of energy homeostasis through AMPK-dependent processes, the design and application of approaches to identify and characterise novel AMPK substrates is invaluable. Here, we report an affinity proteomic-strategy for the discovery and validation of AMPK targets using an antibody to isolate proteins containing the phospho-AMPK substrate recognition motif from hepatocytes that had been treated with pharmacological AMPK activators. We identified 57 proteins that were uniquely enriched in the activator-treated hepatocytes, but were absent in hepatocytes lacking AMPK. We focused on two candidates, cingulin and mitochondrial fission factor (MFF), and further characterised/validated them as AMPK-dependent targets by immunoblotting with phosphorylation site-specific antibodies. A small-molecule AMPK activator caused transient phosphorylation of endogenous cingulin at S137 in intestinal Caco2 cells. Multiple splice-variants of MFF appear to express in hepatocytes and we identified a common AMPK-dependent phospho-site (S129) in all the 3 predominant variants spanning the mass range and a short variant-specific site (S146). Collectively, our proteomic-based approach using a phospho-AMPK substrate antibody in combination with genetic models and selective AMPK activators will provide a powerful and reliable platform for identifying novel AMPK-dependent cellular targets. Copyright © 2015. Published by Elsevier Inc.
    Cellular Signalling 02/2015; 13(5). DOI:10.1016/j.cellsig.2015.02.008 · 4.47 Impact Factor
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    ABSTRACT: Glucagon release from pancreatic alpha cells is required for normal glucose homoeostasis and is dysregulated in both Type 1 and Type 2 diabetes. The tumour suppressor LKB1 (STK11) and the downstream kinase AMP-activated protein kinase (AMPK), modulate cellular metabolism and growth, and AMPK is an important target of the anti-hyperglycaemic agent metformin. While LKB1 and AMPK have emerged recently as regulators of beta cell mass and insulin secretion, the role of these enzymes in the control of glucagon production in vivo is unclear. Here, we ablated LKB1 (αLKB1KO), or the catalytic alpha subunits of AMPK (αAMPKdKO, -α1KO, -α2KO), selectively in ∼45% of alpha cells in mice by deleting the corresponding flox'd alleles with a preproglucagon promoter (PPG) Cre. Blood glucose levels in male αLKB1KO mice were lower during intraperitoneal glucose, aminoimidazole carboxamide ribonucleotide (AICAR) or arginine tolerance tests, and glucose infusion rates were increased in hypoglycemic clamps (p < 0.01). αLKB1KO mice also displayed impaired hypoglycemia-induced glucagon release. Glucose infusion rates were also elevated (p < 0.001) in αAMPKα1 null mice, and hypoglycemia-induced plasma glucagon increases tended to be lower (p = 0.06). Glucagon secretion from isolated islets was sensitized to the inhibitory action of glucose in αLKB1KO, αAMPKdKO, and -α1KO, but not -α2KO islets. An LKB1-dependent signalling cassette, involving but not restricted to AMPKα1, is required in pancreatic alpha cells for the control of glucagon release by glucose.
    01/2015; 4(4). DOI:10.1016/j.molmet.2015.01.006
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    ABSTRACT: The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα mdKO mice displayed normal respiratory exchange ratio (RER) when fed chow or a high-fat diet, or with prolonged fasting. However, in vivo treadmill exercise at the same relative intensity induced a higher RER in AMPKα mdKO mice compared to wild-type (WT = 0.81 ± 0.01 (sem); mdKO = 0.87 ± 0.02 (sem); P < 0.01), indicating a decreased utilization of FA. Further, ex vivo contraction-induced FA oxidation was impaired in AMPKα mdKO muscle, suggesting that the increased RER during exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 (cluster of differentiation 36) and FABPpm (plasma membrane fatty acid binding protein) (by ∼17-40%), together with fully abolished TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) Ser(237) phosphorylation during contraction/exercise in AMPKα mdKO mice, may impair FA transport capacity and FA transport protein translocation to sarcolemma, respectively. AMPKα is thus required for normal FA metabolism during exercise and muscle contraction.-Fentz, J., Kjøbsted, R., Birk, J. B., Jordy, A. B., Jeppesen, J., Thorsen, K., Schjerling, P., Kiens, B., Jessen, N., Viollet, B., Wojtaszewski, J. F. P. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice. © FASEB.
    The FASEB Journal 01/2015; 29(5). DOI:10.1096/fj.14-266650 · 5.48 Impact Factor
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    ABSTRACT: Naive T cells undergo metabolic reprogramming to support the increased energetic and biosynthetic demands of effector T cell function. However, how nutrient availability influences T cell metabolism and function remains poorly understood. Here we report plasticity in effector T cell metabolism in response to changing nutrient availability. Activated T cells were found to possess a glucose-sensitive metabolic checkpoint controlled by the energy sensor AMP-activated protein kinase (AMPK) that regulated mRNA translation and glutamine-dependent mitochondrial metabolism to maintain T cell bioenergetics and viability. T cells lacking AMPKα1 displayed reduced mitochondrial bioenergetics and cellular ATP in response to glucose limitation in vitro or pathogenic challenge in vivo. Finally, we demonstrated that AMPKα1 is essential for T helper 1 (Th1) and Th17 cell development and primary T cell responses to viral and bacterial infections in vivo. Our data highlight AMPK-dependent regulation of metabolic homeostasis as a key regulator of T cell-mediated adaptive immunity. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 01/2015; 42(1). DOI:10.1016/j.immuni.2014.12.030 · 19.75 Impact Factor
  • Diabetes 01/2015; DOI:10.2337/db15-0107 · 8.47 Impact Factor
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    ABSTRACT: Acute exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased cell surface abundance of GLUT4. While increased proximal insulin signaling does not seem to mediate this effect, elevated phosphorylation of TBC1D4, a downstream target of both insulin (Akt) and exercise (AMPK) signaling, appears to play a role. The main purpose of this study was to determine whether AMPK activation increases skeletal muscle insulin sensitivity. We found that prior AICAR stimulation of wild-type mouse muscle increases insulin sensitivity to stimulate glucose uptake. However, this was not observed in mice with reduced or ablated AMPK activity in skeletal muscle. Furthermore, prior AICAR stimulation enhanced insulin-stimulated phosphorylation of TBC1D4 at Thr(649) and Ser(711) in wild-type muscle only. These phosphorylation events were positively correlated with glucose uptake. Our results provide evidence to support that AMPK is sufficient to increase skeletal muscle insulin sensitivity. Moreover, TBC1D4 phosphorylation may facilitate the effect of prior AMPK activation to enhance glucose uptake in response to insulin. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 12/2014; 64(6). DOI:10.2337/db14-1402 · 8.47 Impact Factor
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    ABSTRACT: Dysfunction of complex I (CI) of the mitochondrial electron transport chain (ETC) features prominently in human pathology. Cell models of ETC dysfunction display adaptive survival responses that still are poorly understood but of relevance for therapy development. Here we comprehensively examined how primary human skin fibroblasts adapt to chronic CI inhibition. CI inhibition triggered transient and sustained changes in metabolism, redox homeostasis and mitochondrial (ultra)structure but no cell senescence/death. CI-inhibited cells consumed no oxygen and displayed minor mitochondrial depolarization, reverse-mode action of complex V, a slower proliferation rate and futile mitochondrial biogenesis. Adaptation was neither prevented by antioxidants nor associated with lower ATP or increased PGC1-α/SIRT1/mTOR levels. Survival of CI-inhibited cells was strictly glucose-dependent and accompanied by increased AMPK-α phosphorylation, which occurred without changes in ATP or cytosolic calcium levels. Conversely, cells devoid of AMPK-α died upon CI inhibition. Chronic CI inhibition did not increase mitochondrial superoxide levels or cellular lipid peroxidation and was paralleled by a specific increase in SOD2/GR, whereas SOD1/CAT/Gpx1/Gpx2/Gpx5 levels remained unchanged. Upon hormone stimulation, fully adapted cells displayed aberrant cytosolic and ER calcium handling due to hampered ATP fueling of ER calcium pumps. Using a cell model of CI inhibition we explored the temporal adaptation to CI dysfunction and circumvent problems associated with patient-derived cell systems. It is concluded that CI dysfunction triggers an adaptive program that depends on extracellular glucose and AMPK-α. This response avoids cell death by suppressing energy crisis, oxidative stress induction and substantial mitochondrial depolarization. Copyright © 2014. Published by Elsevier B.V.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 12/2014; 1852(3). DOI:10.1016/j.bbadis.2014.12.012 · 5.09 Impact Factor
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    ABSTRACT: Apoptolidin A was first isolated as a secondary metabolite of a Nocardiopsis sp. and is the founding member of a family of potential selective cancer cell toxins. We now report the isolation, production and pharmacological characterization of apoptolidins A and C from an alternate actinomycete producer, an Amycolatopsis sp. from soil samples collected in Indonesia. We investigated the action of apoptolidins A and C in representative human glioblastoma cells, lung cancer cells and mouse embryonic fibroblasts (MEFs) to better understand the mechanism of action of the known apoptolidins. Shifts in cellular metabolism in intact cells and the status of the AMP-activated protein kinase (AMPK) stress pathway in response to apoptolidin A were entirely consistent with the actions of an ATP synthase inhibitor. We find the metabolic phenotype of the cell to be a critical determinant of apoptolidin sensitivity and the likely basis for cancer cell selectivity. The apoptolidins induce indirect activation of AMPK and trigger autophagy in sensitive cell types without significant inhibition of mTORC1. Human U87-MG glioblastoma cells and wild type MEFs showed increased phosphorylation of AMPK (Thr172), ACC (Ser79) and ULK1 (Ser555), whereas AMPKα-null MEFs and more glycolytic SF-295 glioblastoma cells lacked this response. Although both are reported to be selective inhibitors of mitochondrial ATP synthase, differences between apoptolidin- and oligomycin A-induced responses in cells indicate that the action of these macrolides is not identical. Copyright © 2014. Published by Elsevier Inc.
    Biochemical Pharmacology 12/2014; 93(3). DOI:10.1016/j.bcp.2014.11.015 · 4.65 Impact Factor

Publication Stats

12k Citations
1,852.76 Total Impact Points


  • 2008–2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
  • 2002–2015
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 2001–2015
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2004–2014
    • Institut Cochin
      Lutetia Parisorum, Île-de-France, France
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 2001–2014
    • French Institute of Health and Medical Research
      • Cochin Institute
      Lutetia Parisorum, Île-de-France, France
  • 2006–2013
    • Catholic University of Louvain
      • • Institute of Experimental and Clinical Research (IREC)
      • • Institut de Duve
      Walloon Region, Belgium
    • The University of Tennessee Medical Center at Knoxville
      • Department of Surgery
      Knoxville, Tennessee, United States
    • SRI International
      Menlo Park, California, United States
  • 2012
    • Université Paris-Sorbonne - Paris IV
      Lutetia Parisorum, Île-de-France, France
    • University Pompeu Fabra
      • Department of Experimental and Health Sciences
      Barcino, Catalonia, Spain
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China
    • University of Oklahoma Health Sciences Center
      • Section of Molecular Medicine
      Oklahoma City, OK, United States
  • 2011
    • Università degli Studi di Bari Aldo Moro
      Bari, Apulia, Italy
    • Baylor College of Medicine
      • Department of Molecular & Cellular Biology
      Houston, Texas, United States
  • 2010
    • Jinan University (Guangzhou, China)
      Shengcheng, Guangdong, China
  • 2006–2008
    • Karolinska Institutet
      • Department of Molecular Medicine and Surgery
      Solna, Stockholm, Sweden
  • 2006–2007
    • University of Dundee
      • Division of Signal Transduction Therapy (DSTT)
      Dundee, Scotland, United Kingdom
  • 2005
    • University of Lausanne
      Lausanne, Vaud, Switzerland
  • 2003
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States