Georg Häcker

Universitätsklinikum Freiburg, Freiburg an der Elbe, Lower Saxony, Germany

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Publications (133)767.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The Chlamydiales are an order of obligate intracellular bacteria sharing a developmental cycle inside a cytosolic vacuole, with very diverse natural hosts from amoebae to mammals. The clinically most important species is Chlamydia trachomatis. Many uncertainties remain how Chlamydia organizes its intracellular development and replication. The discovery of new Chlamydiales species from other families permits the comparative analysis of cell biological events and may indicate events that are common to all or peculiar to some species and more or less tightly linked to 'chlamydial' development. We use this approach in the infection of human cells with Waddlia chondrophila, a species from the family Waddliaceae of uncertain natural host. Compared to C. trachomatis, W. chondrophila had slightly different growth characteristics, including faster cytotoxicity. The embedding in cytoskeletal structures was not as pronounced as for the C. trachomatis inclusion. C. trachomatis-infection generates proteolytic activity by the protease CPAF that degrades host substrates upon extraction; these substrates were not cleaved in the case of W. chondrophila. Unlike Chlamydia, W. chondrophila did not protect against staurosporine-induced apoptosis. C. trachomatis-infection causes Golgi-fragmentation and redirects post-Golgi sphingomyelin-transport to the inclusion; both was absent from W. chondrophila-infected cells. When host cells were infected with both species, growth of both species was reduced. This study highlights differences between bacterial species that both depend on obligate intracellular replication inside an inclusion. Some features seem principally dispensable for intracellular development of Chlamydiales in vitro but may be linked to host adaptation of Chlamydia and the higher virulence of C. trachomatis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Infection and immunity 06/2015; 83(8). DOI:10.1128/IAI.00322-15 · 3.73 Impact Factor
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    ABSTRACT: Cell death on extended mitotic arrest is considered arguably most critical for the efficacy of microtubule-targeting agents (MTAs) in anticancer therapy. While the molecular machinery controlling mitotic arrest on MTA treatment, the spindle assembly checkpoint (SAC), appears well defined, the molecular components executing cell death, as well as factors connecting both networks remain poorly understood. Here we conduct a mini screen exploring systematically the contribution of individual BCL2 family proteins at single cell resolution to death on extended mitotic arrest, and demonstrate that the mitotic phosphorylation of BCL2 and BCLX represent a priming event for apoptosis that is ultimately triggered by NOXA-dependent MCL1 degradation, enabling BIM-dependent cell death. Our findings provide a comprehensive model for the initiation of apoptosis in cells stalled in mitosis and provide a molecular basis for the increased efficacy of combinatorial treatment of cancer cells using MTAs and BH3 mimetics.
    Nature Communications 04/2015; 6:6891. DOI:10.1038/ncomms7891 · 11.47 Impact Factor
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    ABSTRACT: The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM). In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM) indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20) by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knock-downs of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated.
    PLoS ONE 04/2015; 10(4):e0123341. DOI:10.1371/journal.pone.0123341 · 3.23 Impact Factor
  • Georg Häcker
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    ABSTRACT: During ER-stress, one of the responses a cell can choose is apoptosis. Apoptosis generally is a cell’s preferred response when other control mechanisms are overwhelmed. We now have a reasonably clear molecular picture what is happening once the apoptotic apparatus has been started. Unclear however are the majority of the upstream pathways that connect other signalling to apoptosis. During ER-stress, confirmed apoptosis-regulating targets are pro- and anti-apoptotic proteins of the Bcl-2-family, whose concerted action induces apoptosis. I will here discuss how mitochondrial apoptosis is triggered, how this is linked to the ER-stress response and in what way this may be relevant during microbial infections.
    Microbes and Infection 10/2014; 16(10). DOI:10.1016/j.micinf.2014.08.009 · 2.86 Impact Factor
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    ABSTRACT: Chlamydia trachomatis is an obligate intracellular human pathogen that grows inside a membranous, cytosolic vacuole termed an inclusion. Septins are a group of 13 GTP-binding proteins that assemble into oligomeric complexes and that can form higher-order filaments. We report here that the septins SEPT2, -9, -11, and probably -7 form fibrillar structures around the chlamydial inclusion. Colocalization studies suggest that these septins combine with F actin into fibers that encase the inclusion. Targeting the expression of individual septins by RNA interference (RNAi) prevented the formation of septin fibers as well as the recruitment of actin to the inclusion. At the end of the developmental cycle of C. trachomatis, newly formed, infectious elementary bodies are released, and this release occurs at least in part through the organized extrusion of intact inclusions. RNAi against SEPT9 or against the combination of SEPT2/7/9 substantially reduced the number of extrusions from a culture of infected HeLa cells. The data suggest that a higher-order structure of four septins is involved in the recruitment or stabilization of the actin coat around the chlamydial inclusion and that this actin recruitment by septins is instrumental for the coordinated egress of C. trachomatis from human cells. The organization of F actin around parasite-containing vacuoles may be a broader response mechanism of mammalian cells to the infection by intracellular, vacuole-dwelling pathogens.
    mBio 08/2014; 5(5). DOI:10.1128/mBio.01802-14 · 6.79 Impact Factor
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    ABSTRACT: The c-MYC (MYC afterward) oncogene is well known for driving numerous oncogenic programs. However, MYC can also induce apoptosis and this function of MYC warrants further clarification. We report here that a clinically relevant proteasome inhibitor significantly increases MYC protein levels and that endogenous MYC is necessary for the induction of apoptosis. This kind of MYC-induced cell death is mediated by enhanced expression of the pro-apoptotic BCL2 family members NOXA and BIM. Quantitative promoter-scanning chromatin immunoprecipitations (qChIP) further revealed binding of MYC to the promoters of NOXA and BIM upon proteasome inhibition, correlating with increased transcription. Both promoters are further characterized by the presence of tri-methylated lysine 4 of histone H3, marking active chromatin. We provide evidence that in our apoptosis models cell death occurs independently of p53 or ARF. Furthermore, we demonstrate that recruitment of MYC to the NOXA as well as to the BIM gene promoters depends on MYC's interaction with the zinc finger transcription factor EGR1 and an EGR1-binding site in both promoters. Our study uncovers a novel molecular mechanism by showing that the functional cooperation of MYC with EGR1 is required for bortezomib-induced cell death. This observation may be important for novel therapeutic strategies engaging the inherent pro-death function of MYC.
    Nucleic Acids Research 08/2014; 42(16). DOI:10.1093/nar/gku763 · 9.11 Impact Factor
  • Georg Häcker · David M. Ojcius · Dagmar Heuer
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    ABSTRACT: It may be worth asking whether all the hoopla about CPAF is justified. Our view is: yes, it is. As in any active scientific area, not every proposal regarding CPAF function has held up. The recent developments are very encouraging: we now have a much better idea of what CPAF can do, but also what it does not do.This article is protected by copyright. All rights reserved.
    Pathogens and Disease 08/2014; 72(1). DOI:10.1111/2049-632X.12211 · 2.40 Impact Factor
  • Aparna R. Shenoy · Susanne Kirschnek · Georg Häcker
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    ABSTRACT: Maintenance of T cells is determined by their survival capacity, which is regulated by Bcl-2 proteins. Cytokines signalling through the common gamma chain such as IL-2, IL-7 and IL-15 are important for T-cell survival but how these cytokines determine the expression of Bcl-2-family proteins is not clear. We report signalling events of cytokines that regulate expression of two key Bcl-2 proteins, pro-apoptotic Bim and anti-apoptotic Mcl-1, in resting C57BL/6 mouse T cells. IL-2, IL-7 and IL-15 inhibited apoptosis but paradoxically induced the expression of Bim, countered by concomitant induction of Mcl-1. Bim induction by IL-15 was found at the mRNA and protein levels and depended on both JAK/STAT and PI3K signals. A new STAT5-binding site was identified in the Bim promoter, which was occupied by STAT5 upon IL-15 stimulation. Although it also depended on JAK/STAT- and PI3K signalling, Mcl-1 regulation was independent of Mcl-1 mRNA levels and of regulation of protein stability, suggesting translational regulation. Concurrent CD3 signals inhibited some of the IL-7 but not the IL-15 effect on Bcl-2 proteins. The data suggest that cytokines induce Bim and prime T cells for apoptosis, but also inhibit apoptosis by stabilising Mcl-1. Later downregulation of short-lived Mcl-1 may induce efficient, Bim-dependent apoptosis.This article is protected by copyright. All rights reserved
    European Journal of Immunology 08/2014; 44(8). DOI:10.1002/eji.201344238 · 4.03 Impact Factor
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    ABSTRACT: Chlamydia grows inside a cytosolic vacuole (the inclusion) that is supplied with nutrients by the host through vesicular and non-vesicular transport. It is unclear in many respects how Chlamydia organizes this transport. One model posits that the Chlamydia-induced fragmentation of the Golgi-apparatus is required for normal transport processes to the inclusion and for chlamydial development, and the chlamydial protease CPAF has been controversially implicated in Golgi-fragmentation. We here use a model of penicillin-induced persistence of infection with Chlamydia trachomatis to test this link. Under penicillin-treatment the inclusion grew in size for the first 24 h but after that growth was severely reduced. Penicillin did not reduce the number of infected cells with fragmented Golgi-apparatus, and normal Golgi-fragmentation was found in a CPAF-deficient mutant. Surprisingly, sphingomyelin transport into the inclusion and into the bacteria, as measured by fluorescence accumulation upon addition of labelled ceramide, was not reduced during penicillin-treatment. Thus, both Golgi-fragmentation and transport of sphingomyelin to C. trachomatis still occurred in this model of persistence. The portion of cells in which CPAF was detected in the cytosol, either by immunofluorescence or by immune-electron microscopy, was drastically reduced in cells cultured in the presence of penicillin. These data argue against an essential role of cytosolic CPAF for Golgi-fragmentation or for sphingomyelin transport in chlamydial infection.
    PLoS ONE 07/2014; 9(7):e103220. DOI:10.1371/journal.pone.0103220 · 3.23 Impact Factor
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    ABSTRACT: Acute graft-versus-host disease (GVHD) considerably limits wider usage of allogeneic hematopoietic cell transplantation (allo-HCT). Antigen-presenting cells and T cells are populations customarily associated with GVHD pathogenesis. Of note, neutrophils are the largest human white blood cell population. The cells cleave chemokines and produce reactive oxygen species, thereby promoting T cell activation. Therefore, during an allogeneic immune response, neutrophils could amplify tissue damage caused by conditioning regimens. We analyzed neutrophil infiltration of the mouse ileum after allo-HCT by in vivo myeloperoxidase imaging and found that infiltration levels were dependent on the local microbial flora and were not detectable under germ-free conditions. Physical or genetic depletion of neutrophils reduced GVHD-related mortality. The contribution of neutrophils to GVHD severity required reactive oxygen species (ROS) because selective Cybb (encoding cytochrome b-245, beta polypeptide, also known as NOX2) deficiency in neutrophils impairing ROS production led to lower levels of tissue damage, GVHD-related mortality and effector phenotype T cells. Enhanced survival of Bcl-xL transgenic neutrophils increased GVHD severity. In contrast, when we transferred neutrophils lacking Toll-like receptor-2 (TLR2), TLR3, TLR4, TLR7 and TLR9, which are normally less strongly activated by translocating bacteria, into wild-type C57BL/6 mice, GVHD severity was reduced. In humans, severity of intestinal GVHD strongly correlated with levels of neutrophils present in GVHD lesions. This study describes a new potential role for neutrophils in the pathogenesis of GVHD in both mice and humans.
    Nature Medicine 05/2014; 20(6). DOI:10.1038/nm.3517 · 27.36 Impact Factor
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    ABSTRACT: We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment.
    PLoS ONE 04/2014; 9(4):e93057. DOI:10.1371/journal.pone.0093057 · 3.23 Impact Factor
  • Georg Häcker
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    ABSTRACT: The protease CPAF is only found in Chlamydiales and in at least most bacteria that share with Chlamydia the biphasic life-style in a cytosolic inclusion. CPAF is intriguing: it appears to be secreted from the inclusion across the inclusion membrane into the cytosol. A bacterial protease ravaging in the cytosol of a human cell may cause a plethora of effects. Curiously, very few are known. The current discussion is bogged down by a focus on experimental artifact, while proposed functions of CPAF remain speculative. I here make the attempt to summarize what we know about CPAF.
    Microbes and Infection 03/2014; 16(5). DOI:10.1016/j.micinf.2014.02.008 · 2.86 Impact Factor
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    ABSTRACT: Inhibitor of apoptosis proteins (IAPs) were originally described to regulate apoptosis by direct binding to caspases. More recently, IAPs have been identified as important modulators of canonical and non-canonical NF-κB signalling via their ubiquitin-E3 ligase activity. IAPs are therefore not only gatekeepers of cell death but probably also involved in the regulation of inflammation as well as innate and adaptive immunity. Here we analysed the role of IAPs in T cell immunity during lymphocytic choriomeningitis virus (LCMV) infection by pharmacological targeting with an IAP-antagonist/Smac-mimetic. Expansion of virus-specific CD8 T cells was drastically reduced in LCMV-infected mice exposed to IAP-antagonist. Accordingly, virus control was substantially impaired, indicated by high virus titres in the spleen and spread of LCMV to peripheral organs. The profound negative effect of IAP-antagonists on T cell immunity was partially linked to TNF-mediated cell death of activated T cells and required inhibition of XIAP as well as cIAP1. Thus, IAPs play an important role in T cell expansion and survival in the context of a highly inflammatory environment such as a virus infection, indicating that IAP-antagonists may interfere with immune responses.
    Blood 12/2013; 123(5). DOI:10.1182/blood-2013-01-479543 · 10.45 Impact Factor
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    ABSTRACT: Purulent pericarditis is a life threatening disease that usually manifests following bacteraemia or through spreading from an intrathoracic focus. Only a few cases of this disease have been reported with Lancefield group C streptococci as etiologic agents, and the primary focus in these infections remains unknown. We report a case of purulent pericarditis with septic and cardiogenic shock, caused by Streptococcus equi subspecies zooepidemicus (group C) in a 51-year-old patient. The pathogen was possibly contracted through contact with horses. Most likely, it initially caused pneumonia before spreading to the pericardium, either directly or via the blood stream. A combined therapeutic approach, consisting of antibiotic therapy and repeated pericardial drainage, was necessary to ensure a clinical cure. After discharge, long-term follow-up for development of constrictive pericarditis is considered mandatory.
    Journal of Medical Microbiology 11/2013; 63(Pt_2). DOI:10.1099/jmm.0.066290-0 · 2.25 Impact Factor
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    ABSTRACT: Neutrophil granulocyte (neutrophil) apoptosis plays a key role in determining inflammation in infectious and non-infectious settings. Recent work has shown that inhibitors of cyclin-dependent kinases (cdk) such as roscovitine can potently induce neutrophil apoptosis and reduce inflammation. Using a conditional Hoxb8-expression system we tested the participation of Bcl-2-family proteins to roscovitine-induced apoptosis in mouse neutrophils and in neutrophil progenitor cells. Bcl-2 strongly protected against roscovitine-induced apoptosis in neutrophils. The isolated loss of either Bim or noxa provided significant, partial protection while protection through combined loss of Bim and noxa or Bim and Puma was only slightly greater than this individual loss. The only substantial change in protein levels observed was the loss of Mcl-1, which was not transcriptional and was inhibited by proteasome blockade. In progenitor cells there was no protection by the loss of Bim alone but substantial protection by the loss of both Bim and Puma; surprisingly, strongest protection was seen by the isolated loss of noxa. The pattern of protein expression and Mcl-1-regulation in progenitor cells was very similar to the one observed in differentiated neutrophils. In addition, roscovitine strongly inhibited proliferation in progenitor cells, associated with an accumulation of cells in G2/M-phase.
    PLoS ONE 11/2013; 8(11):e79352. DOI:10.1371/journal.pone.0079352 · 3.23 Impact Factor
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    ABSTRACT: Sparganosis is a parasitic zoonosis caused by the plerocercoid, i.e. infective larva (sparganum) of pseudophyllidean tapeworms belonging to the genus Spirometra. Human infections with spargana are classified into two forms, non-proliferative sparganosis and proliferative sparganosis. Non-proliferative sparganosis is endemic mainly in East and Southeast Asia (China, Japan, Korea, Taiwan and Thailand) and is caused by S. erinaceieuropaei (S. mansoni) in the Old World and S. mansonoides in the New World. Proliferative sparganosis is caused by the more pathogenic and disseminating Sparganum proliferum and is only sporadically reported from Asia (Japan, Taiwan, Thailand) and very rarely from the New World (Paraguay, Venezuela, United States) This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 10/2013; 170(3). DOI:10.1111/bjd.12679 · 4.28 Impact Factor
  • G Häcker
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    ABSTRACT: Cell death and differentiation is a monthly research journal focused on the exciting field of programmed cell death and apoptosis. It provides a single accessible source of information for both scientists and clinicians, keeping them up-to-date with advances in the field. It encompasses programmed cell death, cell death induced by toxic agents, differentiation and the interrelation of these with cell proliferation.
    Cell death and differentiation 10/2013; 20(10):1289-90. DOI:10.1038/cdd.2013.98 · 8.18 Impact Factor
  • Georg Häcker
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    ABSTRACT: Apoptosis is a well-studied form of cell death in metazoans, where it has a clear role during the life of the (multicellular) animal. Some situations of cell death in unicellular eukaryotes (protozoa and yeast) have also been referred to as apoptosis. In recent years apoptosis has further been identified in bacteria several times. As a bacterial response to external stimuli, apoptosis could be important not only for the bacteria but also to the host. Here I will discuss why I believe that the term apoptosis should be avoided for these situations in bacteria, no matter how interesting the molecular background or how biologically important the underlying mechanism may be.
    Microbes and Infection 06/2013; 15(8-9). DOI:10.1016/j.micinf.2013.05.005 · 2.86 Impact Factor
  • Arnim Weber · David Ausländer · Georg Häcker
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    ABSTRACT: Noxa is a member of the pro-apoptotic BH3-only group of Bcl-2 proteins that is known to bind specifically to anti-apoptotic Mcl-1 and A1, antagonizing their function. Mcl-1 has been reported to have a short half-life, and Noxa up-regulation accelerates Mcl-1 degradation by the proteasome. Unlike human Noxa, mouse Noxa has two BH3-domains, which both have affinity for Mcl-1. We here investigate two aspects of the molecular function of Noxa, namely the requirements for the two BH3-domains in mouse Noxa and the role of Noxa in Mcl-1-degradation. We found that only the C-terminal BH3-domain of mouse Noxa is active in neutralizing Mcl-1. This was the result of the targeting of Noxa to the outer mitochondrial membrane through its C-terminal alpha-helix, which allowed Mcl-1-neutralization only when the BH3-domain was immediately N-terminal of the membrane anchor. However, the N-terminal BH3-domain enhanced interaction with Mcl-1 and A1. The Noxa-dependent degradation of Mcl-1 was independent of the kinase GSK3 and the deubiquitinase Usp9x in mouse embryonic fibroblasts. These data show that Noxa is targeted to the mitochondrial membrane where it neutralises Mcl-1 via its C-terminal BH3-domain and suggest that Noxa is co-degraded with Noxa, in a way independent of ubiquitin-modifying enzymes described for Mcl-1.
    Apoptosis 06/2013; 18(9). DOI:10.1007/s10495-013-0868-9 · 3.69 Impact Factor
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    ABSTRACT: Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3(-/-) mice. Progenitor lines were established and differentiated into neutrophils when Hoxb8 was turned off. G6PC3(-/-) progenitor cells underwent substantial apoptosis when differentiation was started. Transgenic expression of Bcl-XL rescued survival; however, Bcl-XL-protected differentiated cells showed reduced proliferation, immaturity and functional deficiency such as altered MAP kinase signaling and reduced cytokine secretion. Impaired glucose utilization was found and was associated with ER stress and apoptosis, associated with the upregulation of Bim and Bax; downregulation of Bim protected against apoptosis during differentiation. ER-stress further caused a profound loss of expression and secretion of the main neutrophil product neutrophil elastase during differentiation. Transplantation of wild-type Hoxb8-progenitor cells into irradiated mice allowed differentiation into neutrophils in the bone marrow in vivo. Transplantation of G6PC3(-/-) cells yielded few mature neutrophils in bone marrow and peripheral blood. Transgenic Bcl-XL permitted differentiation of G6PC3(-/-) cells in vivo. However, functional deficiencies and differentiation abnormalities remained. Differentiation of macrophages from Hoxb8-dependent progenitors was only slightly disturbed. A combination of defects in differentiation and survival thus underlies neutropenia in G6PC3(-/-) deficiency, both originating from a reduced ability to utilize glucose. Hoxb8-dependent cells are a model to study differentiation and survival of the neutrophil lineage.Cell Death and Differentiation advance online publication, 17 May 2013; doi:10.1038/cdd.2013.39.
    Cell death and differentiation 05/2013; 20(8). DOI:10.1038/cdd.2013.39 · 8.18 Impact Factor

Publication Stats

5k Citations
767.22 Total Impact Points


  • 2013–2015
    • Universitätsklinikum Freiburg
      • Institute of Medical Microbiology and Hygiene
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2009–2014
    • University of Freiburg
      • • Institute of Biochemistry and Molecular Biology
      • • BIOSS Centre for Biological Signalling Studies
      Freiburg, Baden-Württemberg, Germany
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1994–2011
    • The Walter and Eliza Hall Institute of Medical Research
      • Division of Molecular Genetics of Cancer
      Melbourne, Victoria, Australia
  • 1991–2009
    • University of Technology Munich
      • • Institut für Medizinische Mikrobiologie, Immunologie und Hygiene
      • • Institute of Micro Technology and Medical Device Technology
      München, Bavaria, Germany
  • 2006
    • University of Melbourne
      Melbourne, Victoria, Australia
    • University of California, Merced
      • School of Natural Sciences
      Merced, California, United States
  • 1995
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1989
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany