Alexander H Stegh

Northwestern University, Evanston, Illinois, United States

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Publications (29)267.85 Total impact

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    ABSTRACT: Ribozymes are highly structured RNA sequences that can be tailored to recognize and cleave specific stretches of mRNA. Their current therapeutic efficacy remains low due to their large size and structural instability compared to shorter therapeutically relevant RNA such as small interfering RNA (siRNA) and microRNA (miRNA). Herein, a synthetic strategy that makes use of the spherical nucleic acid (SNA) architecture to stabilize ribozymes and transfect them into live cells is reported. The properties of this novel ribozyme-SNA are characterized in the context of the targeted knockdown of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein involved in chemotherapeutic resistance of solid tumors, foremost glioblastoma multiforme (GBM). Data showing the direct cleavage of full-length MGMT mRNA, knockdown of MGMT protein, and increased sensitization of GBM cells to therapy-mediated apoptosis, independent of transfection agents, provide compelling evidence for the promising properties of this new chemical architecture.
    Journal of the American Chemical Society 08/2015; DOI:10.1021/jacs.5b07104 · 12.11 Impact Factor
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    ABSTRACT: Spherical nucleic acids (SNAs) represent an emerging class of nanoparticle-based therapeutics. SNAs consist of densely functionalized and highly oriented oligonucleotides on the surface of a nanoparticle which can either be inorganic (such as gold or platinum) or hollow (such as liposomal or silica-based). The spherical architecture of the oligonucleotide shell confers unique advantages over traditional nucleic acid delivery methods, including entry into nearly all cells independent of transfection agents and resistance to nuclease degradation. Furthermore, SNAs can penetrate biological barriers, including the blood-brain and blood-tumor barriers as well as the epidermis, and have demonstrated efficacy in several murine disease models in the absence of significant adverse side effects. In this chapter, we will focus on the applications of SNAs in cancer therapy as well as discuss multimodal SNAs for drug delivery and imaging.
    Cancer treatment and research 04/2015; 166:23-50. DOI:10.1007/978-3-319-16555-4_2
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    ABSTRACT: Glioblastoma multiforme (GBM) is a lethal, therapy-resistant brain cancer consisting of numerous tumor cell subpopulations, including stem-like glioma-initiating cells (GICs), which contribute to tumor recurrence following initial response to therapy. Here, we identified miR-182 as a regulator of apoptosis, growth, and differentiation programs whose expression level is correlated with GBM patient survival. Repression of Bcl2-like12 (Bcl2L12), c-Met, and hypoxia-inducible factor 2α (HIF2A) is of central importance to miR-182 anti-tumor activity, as it results in enhanced therapy susceptibility, decreased GIC sphere size, expansion, and stemness in vitro. To evaluate the tumor-suppressive function of miR-182 in vivo, we synthesized miR-182-based spherical nucleic acids (182-SNAs); i.e., gold nanoparticles covalently functionalized with mature miR-182 duplexes. Intravenously administered 182-SNAs penetrated the blood-brain/blood-tumor barriers (BBB/BTB) in orthotopic GBM xenografts and selectively disseminated throughout extravascular glioma parenchyma, causing reduced tumor burden and increased animal survival. Our results indicate that harnessing the anti-tumor activities of miR-182 via safe and robust delivery of 182-SNAs represents a novel strategy for therapeutic intervention in GBM. © 2015 Kouri et al.; Published by Cold Spring Harbor Laboratory Press.
    Genes & development 04/2015; 29(7):732-45. DOI:10.1101/gad.257394.114 · 10.80 Impact Factor
  • Article: Preface.
    Cancer treatment and research 01/2015; 166:v-vii.
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    ABSTRACT: This report describes results from our analysis of the activity and biodistribution of a novel pan-ERBB inhibitor, NT113, when used in treating mice with intracranial glioblastoma (GBM) xenografts. Approaches used in this investigation include: bioluminescence imaging (BLI) for monitoring intracranial tumor growth and response to therapy; determination of survival benefit from treatment; analysis of tumor immunohistochemical (IHC) reactivity for indication of treatment effect on proliferation and apoptotic response; western blot for determination of effects of treatment on ERBB and ERBB signaling mediator activation; and high performance liquid chromatography for determination of NT113 concentration in tissue extracts from animals receiving oral administration of inhibitor. Our results show that NT113 is active against GBM xenografts in which wild-type EGFR or EGFRvIII is highly expressed. In experiments including lapatinib and/or erlotinib, NT113 treatment was associated with the most substantial improvement in survival, as well as the most substantial tumor growth inhibition, as indicated by BLI and IHC results. Western blot results indicated that NT113 has inhibitory activity, both in vivo and in vitro, on ERBB family member phosphorylation, as well as on the phosphorylation of downstream signaling mediator Akt. Results from the analysis of animal tissues revealed significantly higher NT113 normal brain-to-plasma and intracranial tumor-to-plasma ratios for NT113, relative to erlotinib, indicating superior NT113 partitioning to intracranial tissue compartments. These data provide a strong rationale for the clinical investigation of NT113, a novel ERBB inhibitor, in treating patients with GBM.
    Molecular Cancer Therapeutics 10/2014; 13(12). DOI:10.1158/1535-7163.MCT-14-0306 · 5.68 Impact Factor
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    ABSTRACT: Rationale: Protein kinase C zeta (PKCζ) has been reported to act as a tumor suppressor. Deletion of PKCζ in experimental cancer models has been shown to increase tumor growth. However, the mechanisms of PKCζ downregulation have in cancerous cells have not been previously described. Objective: To determine the molecular mechanisms that lead to decreased PKCζ expression and thus increased survival in cancer cells and tumors. Measurements and Main Results: Hypoxia is a hallmark of growing solid tumors. We found that during hypoxia, PKCζ is ubiquitinated and degraded via the ubiquitin ligase HOIL-1L, a component of the linear ubiquitin chain assembly complex (LUBAC). In vitro ubiquitination assays indicate the HOIL-1L ubiquitinates PKCζ in Lys-48 targeting it for proteasomal degradation. In a mice xenograft models of lung cancer and flank cancer, we found that silencing of HOIL-1L increased the abundance of PKCζ and decreased the size of tumors, suggesting that lower levels of HOIL-1L promote survival. Indeed, mRNA transcript levels of HOIL-1L levels were elevated in tumor of patients with lung adenocarcinoma and in a lung adenocarcinoma tissue microarray we found that the levels of HOIL-1L were associated with high grade tumors. Moreover, we found that that HOIL-1L expression was regulated by the hypoxia inducible factors. Interestingly the actions of HOIL-1L were independent of HOIP and SHARPIN the other components of LUBAC.
    American Journal of Respiratory and Critical Care Medicine 08/2014; 190(6). DOI:10.1164/rccm.201403-0463OC · 13.00 Impact Factor
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    ABSTRACT: Therapy resistance is a major limitation to the successful treatment of cancer. Here, we identify Bcl2-like 13 (Bcl2L13), an atypical member of the Bcl-2 family, as a therapy susceptibility gene with elevated expression in solid and blood cancers, including glioblastoma (GBM). We demonstrate that mitochondria-associated Bcl2L13 inhibits apoptosis induced by a wide spectrum of chemo- and targeted therapies upstream of Bcl2-associated X protein activation and mitochondrial outer membrane permeabilization in vitro and promotes GBM tumor growth in vivo. Mechanistically, Bcl2L13 binds to proapoptotic ceramide synthases 2 (CerS2) and 6 (CerS6) via a unique C-terminal 250-aa sequence located between its Bcl-2 homology and membrane anchor domains and blocks homo- and heteromeric CerS2/6 complex formation and activity. Correspondingly, CerS2/6 activity and Bcl2L13 abundance are inversely correlated in GBM tumors. Thus, our genetic and functional studies identify Bcl2L13 as a regulator of therapy susceptibility and point to the Bcl2L13-CerS axis as a promising target to enhance responses of therapy-refractory cancers toward conventional and targeted regimens currently in clinical use.
    Proceedings of the National Academy of Sciences 03/2014; 111(15). DOI:10.1073/pnas.1316700111 · 9.67 Impact Factor
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    Chad A Mirkin · Alexander H Stegh
    Oncotarget 12/2013; 5(1). DOI:10.18632/oncotarget.1757 · 6.36 Impact Factor
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    ABSTRACT: Glioblastoma multiforme (GBM) is a neurologically debilitating disease that culminates in death 14 to 16 months after diagnosis. An incomplete understanding of how cataloged genetic aberrations promote therapy resistance, combined with ineffective drug delivery to the central nervous system, has rendered GBM incurable. Functional genomics efforts have implicated several oncogenes in GBM pathogenesis but have rarely led to the implementation of targeted therapies. This is partly because many "undruggable" oncogenes cannot be targeted by small molecules or antibodies. We preclinically evaluate an RNA interference (RNAi)-based nanomedicine platform, based on spherical nucleic acid (SNA) nanoparticle conjugates, to neutralize oncogene expression in GBM. SNAs consist of gold nanoparticles covalently functionalized with densely packed, highly oriented small interfering RNA duplexes. In the absence of auxiliary transfection strategies or chemical modifications, SNAs efficiently entered primary and transformed glial cells in vitro. In vivo, the SNAs penetrated the blood-brain barrier and blood-tumor barrier to disseminate throughout xenogeneic glioma explants. SNAs targeting the oncoprotein Bcl2Like12 (Bcl2L12)-an effector caspase and p53 inhibitor overexpressed in GBM relative to normal brain and low-grade astrocytomas-were effective in knocking down endogenous Bcl2L12 mRNA and protein levels, and sensitized glioma cells toward therapy-induced apoptosis by enhancing effector caspase and p53 activity. Further, systemically delivered SNAs reduced Bcl2L12 expression in intracerebral GBM, increased intratumoral apoptosis, and reduced tumor burden and progression in xenografted mice, without adverse side effects. Thus, silencing antiapoptotic signaling using SNAs represents a new approach for systemic RNAi therapy for GBM and possibly other lethal malignancies.
    Science translational medicine 10/2013; 5(209):209ra152. DOI:10.1126/scitranslmed.3006839 · 15.84 Impact Factor
  • Alexander H Stegh
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    ABSTRACT: Tumors are composed of highly proliferate, migratory, invasive, and therapy-evading cells. These characteristics are conferred by an enormously complex landscape of genomic, (epi-)genetic, and proteomic aberrations. Recent efforts to comprehensively catalogue these reversible and irreversible modifications have began to identify molecular mechanisms that contribute to cancer pathophysiology, serve as novel therapeutic targets, and may constitute biomarkers for early diagnosis and prediction of therapy responses. With constantly evolving technologies that will ultimately enable a complete survey of cancer genomes, the challenges for discovery cancer science and drug development are daunting. Bioinformatic and functional studies must differentiate cancer-driving and -contributing mutations from mere bystanders or 'noise', and have to delineate their molecular mechanisms of action as a function of collaborating oncogenic and tumor suppressive signatures. In addition, the translation of these genomic discoveries into meaningful clinical endpoints requires the development of co-extinction strategies to therapeutically target multiple cancer genes, to robustly deliver therapeutics to tumor sites, and to enable widespread dissemination of therapies within tumor tissue. In this perspective, I will describe the most current paradigms to study and validate cancer gene function. I will highlight advances in the area of nanotechnology, in particular, the development of RNA interference (RNAi)-based platforms to more effectively deliver therapeutic agents to tumor sites, and to modulate critical cancer genes that are difficult to target using conventional small-molecule- or antibody-based approaches. I will conclude with an outlook on the deluge of challenges that genomic and bioengineering sciences must overcome to make the long-awaited era of personalized nano-medicine a clinical reality for cancer patients.
    Integrative Biology 08/2012; 5(1). DOI:10.1039/c2ib20104f · 3.76 Impact Factor
  • Cancer Research 06/2012; 72(8 Supplement):2005-2005. DOI:10.1158/1538-7445.AM2012-2005 · 9.33 Impact Factor
  • Fotini M. Kouri · Yongfei Wu · Lynda Chin · Alexander H. Stegh
    Cancer Research 04/2012; 72(8 Supplement):1107-1107. DOI:10.1158/1538-7445.AM2012-1107 · 9.33 Impact Factor
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    Fotini M Kouri · Samuel A Jensen · Alexander H Stegh
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    ABSTRACT: Glioblastoma (GBM) is a highly aggressive and lethal brain cancer with a median survival of less than two years after diagnosis. Hallmarks of GBM tumors include soaring proliferative indices, high levels of angiogenesis, diffuse invasion into normal brain parenchyma, resistance toward therapy-induced apoptosis, and pseudopallisading necrosis. Despite the recent advances in neurosurgery, radiation therapy, and the development of targeted chemotherapeutic regimes, GBM remains one of the deadliest types of cancer. Particularly, the alkylating agent temozolomide (TMZ) in combination with radiation therapy prolonged patient survival only marginally, and clinical studies assessing efficacies of targeted therapies, foremost ATP mimetics inhibiting the activity of receptor tyrosine kinases (RTKs), revealed only few initial responders; tumor recurrence is nearly universal, and salvage therapies to combat such progression remain ineffective. Consequently, myriad preclinical and clinical studies began to define the molecular mechanisms underlying therapy resistance of GBM tumors, and pointed to the Bcl-2 protein family, in particular the atypical member Bcl2-Like 12 (Bcl2L12), as important regulators of therapy-induced cell death. This review will discuss the multi-faceted modi operandi of Bcl-2 family proteins, describe their roles in therapy resistance of malignant glioma, and outline current and future drug development efforts to therapeutically target Bcl-2 proteins.
    The Scientific World Journal 02/2012; 2012:838916. DOI:10.1100/2012/838916 · 1.73 Impact Factor
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    Alexander H Stegh
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    ABSTRACT: INTRODUCTION: Research over the past three decades has identified p53 as a multi-functional transcription factor. p53 influences myriad, highly diverse cellular processes, and represents one of the most important and extensively studied tumor suppressors. Activated by various stresses, p53 blocks cancer progression by provoking transient or permanent growth arrest, by enabling DNA repair, or by advancing cellular death programs. This anti-cancer activity profile, together with genomic and mutational analyses documenting inactivation of p53 in more than 50% of human cancers, motivated drug development efforts to (re-) activate p53 in established tumors. AREAS COVERED: The complexities of p53 signaling in cancer are summarized, including current strategies and challenges to restore p53's tumor suppressive function in established tumors, to inactivate p53 inhibitors, and to restore wild type function of p53 mutant proteins. EXPERT OPINION: p53 represents an attractive target for the development of anti-cancer therapies. Whether p53 is 'druggable', however, remains an area of active research and discussion, as p53 has pro-survival functions and chronic p53 activation accelerates aging, which may compromise the long-term homeostasis of an organism. The complex biology and dual functions of p53 in cancer prevention and age-related cellular responses pose significant challenges to the development of p53-targeting cancer therapies.
    Expert Opinion on Therapeutic Targets 01/2012; 16(1):67-83. DOI:10.1517/14728222.2011.643299 · 5.14 Impact Factor
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    ABSTRACT: Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression. Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFβ/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.
    Nature 02/2011; 470(7333):269-73. DOI:10.1038/nature09677 · 41.46 Impact Factor
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    Alexander H Stegh · Ronald A DePinho
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    ABSTRACT: Malignant gliomas are the most common and lethal primary central nervous system cancer. Glioblastoma mutliforme (GBM), the most aggressive of these neoplasms, are generally lethal within 2 years of diagnosis due in part to the intense apoptosis resistance of its cancer cells, hence poor therapeutic response to conventional and targeted therapies. Twenty years of research has uncovered key genetic events involved in disease initiation and progression, foremost the Tp53 tumor suppressor that is mutated or deleted in 35% of GBM. The prime importance of p53 signaling for gliomapathogenesis is further evidenced by epistatic genetic events targeting additional pathway components including deletion of p14 (Arf) (CDKN2A) and amplification of the p53-degrading ubiquitin ligases MDM2 and MDM4. Recent studies have identified and validated Bcl2-Like 12 (Bcl2L12) as a potent glioma oncoprotein with multiple strategic points in apoptosis regulatory networks, i.e. effector caspases and the p53 tumor suppressor. Bcl2L12 resides in both the cytoplasm and nucleus. In the cytoplasm, Bcl2L12 functions to inhibit caspases 3 and 7, in the nucleus, Bcl2L12 forms a complex with p53, modestly reduces p53 protein stability and prevents its binding to selected target gene promoter (e.g. p21, DR5, Noxa and PUMA), thereby inhibiting p53-directed transcriptomic changes upon DNA damage. Proteomic and multidimensional oncogenomic analyses confirmed a Bcl2L12-p53 signaling axis in GBM, as Bcl2L12 exhibited predominant genomic amplification, elevated mRNA and protein levels in GBM tumors with uncompromised p53 function. On the cell biological level, Bcl2L12 exerts robust inhibition of p53-dependent senescence and apoptosis processes in glioma cells. These multi-leveled studies establish Bcl2L12 as an important oncoprotein acting at the intersection of nuclear p53 and cytoplasmic caspase signaling and point to pharmacological disruption of the Bcl2L12:p53 complex as a promising novel therapeutic strategy for the enhanced treatment of GBM.
    Cell cycle (Georgetown, Tex.) 01/2011; 10(1):33-8. DOI:10.4161/cc.10.1.14365 · 4.57 Impact Factor
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    ABSTRACT: Glioblastoma multiforme (GBM) is a lethal brain tumor characterized by intense apoptosis resistance and extensive necrosis. Bcl2L12 (for Bcl2-like 12) is a cytoplasmic and nuclear protein that is overexpressed in primary GBM and functions to inhibit post-mitochondrial apoptosis signaling. Here, we show that nuclear Bcl2L12 physically and functionally interacts with the p53 tumor suppressor, as evidenced by the capacity of Bcl2L12 to (1) enable bypass of replicative senescence without concomitant loss of p53 or p19 (Arf), (2) inhibit p53-dependent DNA damage-induced apoptosis, (3) impede the capacity of p53 to bind some of its target gene promoters, and (4) attenuate endogenous p53-directed transcriptomic changes following genotoxic stress. Correspondingly, The Cancer Genome Atlas profile and tissue protein analyses of human GBM specimens show significantly lower Bcl2L12 expression in the setting of genetic p53 pathway inactivation. Thus, Bcl2L12 is a multifunctional protein that contributes to intense therapeutic resistance of GBM through its ability to operate on two key nodes of cytoplasmic and nuclear signaling cascades.
    Genes & development 10/2010; 24(19):2194-204. DOI:10.1101/gad.1924710 · 10.80 Impact Factor
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    Alexander H Stegh · Lynda Chin · David N Louis · Ronald A DePinho
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    ABSTRACT: Glioblastoma (GBM) is the most common type of primary brain cancer and carries a dismal prognosis primarily due to the emergence of resistance towards extant radiation, conventional and targeted chemotherapies. Although GBM resists therapy-induced apoptosis, tumors show a seemingly paradoxical propensity for florid intratumoral necrogenesis. This necrosis manifests pathologically as microscopic foci or confluent expanses of necrotic tumor. While it is now well recognized that necrosis is an active cell death process and that apoptosis and necrosis death modalities are intertwined on multiple levels, the precise molecular mechanisms and genetic elements underlying these forms of cell death in GBM remain areas of active investigation. In recent oncogenomic studies, we identified a novel GBM oncoprotein, Bcl2-Like 12 (Bcl2L12), which is significantly expressed in the majority of primary GBM tumor specimens and distantly related to canonical Bcl-2 proteins. Due to its distinctive impact on cell death signaling, Bcl2L12 phenocopies pro-necrotic and anti-apoptotic propensities of high grade glioma: Mechanistically, we determined that unlike prototypic Bcl-2 family members, Bcl2L12 does not safeguard mitochondrial membrane integrity, but instead potently inhibits apoptosis at the level of post-mitochondrial effector caspase-3/7 activation. A combination of enforced expression, RNAi-mediated extinction, co-localization and protein interaction studies revealed that Bcl2L12 inhibits caspases 3 and 7 via distinct mechanisms. Direct physical interaction underlies Bcl2L12's inhibition of caspase-7 processing, whereas Bcl2L12-induced transcriptional upregulation of the small heat shock protein alpha B-crystallin is instrumental to neutralization of caspase-3 activation. Mirroring the cellular phenotype elicited by energy depletion, genetic or pharmacologic inhibition of post-mitochondrial apoptosis signaling molecules, Bcl2L12 promotes necrogenesis in glial cells in the context of a proapoptotic stimulus establishing that it represents a novel regulator of the balance between apoptosis and necrosis in GBM.
    Cell cycle (Georgetown, Tex.) 10/2008; 7(18):2833-9. DOI:10.4161/cc.7.18.6759 · 4.57 Impact Factor
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    ABSTRACT: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer that is characterized by the paradoxical features of intense apoptosis resistance yet a marked propensity to undergo necrosis. Bcl2L12 (for Bcl2-Like12) is a nuclear and cytoplasmic oncoprotein that is universally overexpressed in primary GBM and functions to block postmitochondrial apoptosis signaling by neutralizing effector caspase-3 and caspase-7 maturation. This postmitochondrial block in apoptosis engenders the alternate cell fate of cellular necrosis, thus providing a molecular explanation for GBM's classical features. Whereas Bcl2L12-mediated neutralization of caspase-7 maturation involves physical interaction, the mechanism governing Bcl2L12-mediated inhibition of caspase-3 activity is not known. The nuclear localization of Bcl2L12 prompted expression profile studies of primary astrocytes engineered to overexpress Bcl2L12. The Bcl2L12 transcriptome revealed a striking induction of the small heat shock protein α-basic-crystallin (αB-crystallin/HspB5), a link reinforced by robust αB-crystallin expression in Bcl2L12-expressing orthotopic glioma and strong coexpression of αB-crystallin and Bcl2L12 proteins in human primary GBMs. On the functional level, enforced αB-crystallin or Bcl2L12 expression enhances orthotopic tumor growth. Conversely, RNAi-mediated knockdown of αB-crystallin in Bcl2L12-expressing astrocytes and glioma cell lines with high endogenous B-crystallin showed enhanced apoptosis, yet decreased necrotic cell death with associated increased caspase-3 but not caspase-7 activation. Mirroring this specific effect on effector caspase-3 activation, αB-crystallin selectively binds procaspase-3 and its cleavage intermediates in vitro and in vivo. Thus, αB-crystallin is a Bcl2L12-induced oncoprotein that enables Bcl2L12 to block the activation of both effector caspases via distinct mechanisms, thereby contributing to GBM pathogenesis and its hallmark biological properties.
    Proceedings of the National Academy of Sciences 09/2008; 105(31):10703-8. DOI:10.1073/pnas.0712034105 · 9.67 Impact Factor
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    ABSTRACT: Malignant astrocytic gliomas such as glioblastoma are the most common and lethal intracranial tumors. These cancers exhibit a relentless malignant progression characterized by widespread invasion throughout the brain, resistance to traditional and newer targeted therapeutic approaches, destruction of normal brain tissue, and certain death. The recent confluence of advances in stem cell biology, cell signaling, genome and computational science and genetic model systems have revolutionized our understanding of the mechanisms underlying the genetics, biology and clinical behavior of glioblastoma. This progress is fueling new opportunities for understanding the fundamental basis for development of this devastating disease and also novel therapies that, for the first time, portend meaningful clinical responses.
    Genes & Development 12/2007; 21(21):2683-710. DOI:10.1101/gad.1596707 · 10.80 Impact Factor

Publication Stats

3k Citations
267.85 Total Impact Points


  • 2011–2014
    • Northwestern University
      • • The Ken and Ruth Davee Department of Neurology
      • • Department of Chemistry
      Evanston, Illinois, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2012
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
  • 2007–2008
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2001–2002
    • University of Chicago
      • Ben May Department for Cancer Research
      Chicago, IL, United States
  • 1998
    • German Cancer Research Center
      • Division of Molecular Biology of the Cell II
      Heidelburg, Baden-Württemberg, Germany