M Simon

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc Hypoxic reactive oxygen species regulate the integrated stress response and cell survival
    Liping Liu
    Howard Hughes Medical Institute, USA
    J Biol Chem 283:31153-62. 2008
  2. pmc Functional analysis of the Cdk7.cyclin H.Mat1 complex in mouse embryonic stem cells and embryos
    Shetal A Patel
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:15587-98. 2010
  3. pmc Nutrient-sensing pathways and metabolic regulation in stem cells
    Joshua D Ochocki
    Abramson Family Cancer Research Institute, 2 Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104
    J Cell Biol 203:23-33. 2013
  4. pmc Loss of the Birt-Hogg-Dubé tumor suppressor results in apoptotic resistance due to aberrant TGFβ-mediated transcription
    T P Cash
    Abramson Family Cancer Research Institute, Philadelphia, PA, USA
    Oncogene 30:2534-46. 2011
  5. pmc O(2) regulates skeletal muscle progenitor differentiation through phosphatidylinositol 3-kinase/AKT signaling
    Amar J Majmundar
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Mol Cell Biol 32:36-49. 2012
  6. ncbi request reprint Mitochondrial reactive oxygen species are required for hypoxic HIF alpha stabilization
    M Celeste Simon
    Howard Hughes Medical Institute, Dept of Cell and Dev Biology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6160, USA
    Adv Exp Med Biol 588:165-70. 2006
  7. pmc The role of oxygen availability in embryonic development and stem cell function
    M Celeste Simon
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Mol Cell Biol 9:285-96. 2008
  8. ncbi request reprint Vascular morphogenesis and the formation of vascular networks
    M Celeste Simon
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania, 456 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Dev Cell 6:479-82. 2004
  9. pmc Hypoxia-induced signaling in the cardiovascular system
    M Celeste Simon
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Annu Rev Physiol 70:51-71. 2008
  10. pmc C1qRp defines a new human stem cell population with hematopoietic and hepatic potential
    Guenahel H Danet
    Howard Hughes Medical Institute and Abramson Family Cancer Research Institute, Molecular Cardiology Research Center, University of Pennsylvania School of Medicine, BRB 2 3, 421 Curie Boulevard, Philadelphia, PA 19104 6160, USA
    Proc Natl Acad Sci U S A 99:10441-5. 2002

Collaborators

Detail Information

Publications82

  1. pmc Hypoxic reactive oxygen species regulate the integrated stress response and cell survival
    Liping Liu
    Howard Hughes Medical Institute, USA
    J Biol Chem 283:31153-62. 2008
    ..Collectively, our data support an important role for ROS in hypoxic cell survival. Under conditions of moderate hypoxia, ROS induce the ISR, thereby promoting energy and redox homeostasis and enhancing cellular survival...
  2. pmc Functional analysis of the Cdk7.cyclin H.Mat1 complex in mouse embryonic stem cells and embryos
    Shetal A Patel
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:15587-98. 2010
    ..Collectively, these studies demonstrate a critical and novel role for cyclin H in maintaining ES cell identity and suggest that cyclin H has important functions in early embryonic development...
  3. pmc Nutrient-sensing pathways and metabolic regulation in stem cells
    Joshua D Ochocki
    Abramson Family Cancer Research Institute, 2 Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104
    J Cell Biol 203:23-33. 2013
    ..Recent progress has detailed the molecular mechanisms of this metabolic phenotype and has offered insight into new metabolic pathways that may be involved in stem cell homeostasis. ..
  4. pmc Loss of the Birt-Hogg-Dubé tumor suppressor results in apoptotic resistance due to aberrant TGFβ-mediated transcription
    T P Cash
    Abramson Family Cancer Research Institute, Philadelphia, PA, USA
    Oncogene 30:2534-46. 2011
    ..In aggregate, this work identifies a specific tumor suppressive mechanism for BHD in regulating TGFβ-dependent transcription and apoptosis, which has implications for the development of targeted therapies...
  5. pmc O(2) regulates skeletal muscle progenitor differentiation through phosphatidylinositol 3-kinase/AKT signaling
    Amar J Majmundar
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Mol Cell Biol 32:36-49. 2012
    ..O(2) deprivation affects AKT activity by reducing insulin-like growth factor I receptor sensitivity to growth factors. We conclude that AKT represents a key molecular link between O(2) and skeletal muscle differentiation...
  6. ncbi request reprint Mitochondrial reactive oxygen species are required for hypoxic HIF alpha stabilization
    M Celeste Simon
    Howard Hughes Medical Institute, Dept of Cell and Dev Biology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6160, USA
    Adv Exp Med Biol 588:165-70. 2006
    ..The cytochrome c mutant embryonic cells provide a unique reagent to further dissect the role of mitochondria in O2 mediated-intracellular events...
  7. pmc The role of oxygen availability in embryonic development and stem cell function
    M Celeste Simon
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Mol Cell Biol 9:285-96. 2008
    ..These findings have important implications for the development of therapies for tissue regeneration and disease...
  8. ncbi request reprint Vascular morphogenesis and the formation of vascular networks
    M Celeste Simon
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania, 456 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Dev Cell 6:479-82. 2004
    ..Participants enjoyed lively discussions on developmental vascular biology while experiencing the natural beauty of the Pacific Coast...
  9. pmc Hypoxia-induced signaling in the cardiovascular system
    M Celeste Simon
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Annu Rev Physiol 70:51-71. 2008
    ..Here, we describe HIF-independent responses and how they impact cardiovascular tissue homeostasis...
  10. pmc C1qRp defines a new human stem cell population with hematopoietic and hepatic potential
    Guenahel H Danet
    Howard Hughes Medical Institute and Abramson Family Cancer Research Institute, Molecular Cardiology Research Center, University of Pennsylvania School of Medicine, BRB 2 3, 421 Curie Boulevard, Philadelphia, PA 19104 6160, USA
    Proc Natl Acad Sci U S A 99:10441-5. 2002
    ..These findings may have important scientific and clinical implications in the field of human stem cell biology and transplantation...
  11. ncbi request reprint Hypoxia affects mesoderm and enhances hemangioblast specification during early development
    Diana L Ramirez-Bergeron
    Howard Hughes Medical Institute and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Development 131:4623-34. 2004
    ..Together these data suggest that ineffective responses to hypoxia in Arnt(-/-) embryos abrogate proper cardiovascular development during early embryogenesis, including the pathways controlling hemangioblast differentiation...
  12. ncbi request reprint HIFs, hypoxia, and vascular development
    Kelly L Covello
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Curr Top Dev Biol 62:37-54. 2004
    ..Abnormal HIF expression is related to numerous diseases of the vascular system, including heart disease, cancer, and chronic obstructive pulmonary disease...
  13. ncbi request reprint Hypoxic reduction in cellular glutathione levels requires mitochondrial reactive oxygen species
    Kyle D Mansfield
    Abramson Family Cancer Research Institute, 438 BRB II III, 421 Curie Blvd, Philadelphia, PA 19104, USA
    J Appl Physiol 97:1358-66. 2004
    ..Overall, these data suggest a novel HIF-independent role for mitochondrial ROS in regulating glutathione synthesis, and hence cellular oxidative homeostasis, during hypoxic exposure...
  14. ncbi request reprint Lasting longer without oxygen: The influence of hypoxia on Notch signaling
    Warren S Pear
    Abramson Family Cancer Research Institute, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 8:435-7. 2005
    ..provide important new information on this topic by showing that hypoxia enhances Notch signaling due to the association of Notch and HIF-1alpha. This interaction may have important consequences for tumor cell growth...
  15. pmc Hypoxia-inducible factors, stem cells, and cancer
    Brian Keith
    Abramson Family Cancer Research Institute, University of Pennsylvania, 453 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Cell 129:465-72. 2007
    ..As many cancers are thought to develop from a small number of transformed, self-renewing, and multipotent "cancer stem cells," these results suggest new roles for HIFs in tumor progression...
  16. pmc Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation
    Kyle D Mansfield
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cell Metab 1:393-9. 2005
    ..These results provide genetic evidence indicating that mtROS act upstream of prolyl hydroxylases in regulating HIF-1 alpha and HIF-2 alpha in this O(2)-sensing pathway...
  17. pmc Expansion of human SCID-repopulating cells under hypoxic conditions
    Guenahel H Danet
    Division of Hematology Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6160, USA
    J Clin Invest 112:126-35. 2003
    ..The use of low O2 levels to enhance the survival and/or self-renewal of human BM HSCs in vitro represents an important advance and could have valuable clinical implications...
  18. pmc Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression
    Karen D Cowden Dahl
    Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, Philadelphia, 19104, USA
    Mol Biol Cell 16:1901-12. 2005
    ..Together, these data suggest that HIF and O(2) tension influence placental invasion and tumor migration by increasing cell surface expression of alphavbeta3 integrin...
  19. pmc HIF2alpha inhibition promotes p53 pathway activity, tumor cell death, and radiation responses
    Jessica A Bertout
    Abramson Family Cancer Research Institute, Abramson Cancer Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 106:14391-6. 2009
    ..These results correlate with altered p53 phosphorylation and target gene expression in untreated human tumor samples and show that HIF2alpha likely contributes to tumor cell survival including during radiation therapy...
  20. pmc HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity
    John D Gordan
    Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Cancer Cell 11:335-47. 2007
    ..Enhanced c-Myc activity likely contributes to HIF-2alpha-mediated neoplastic progression following loss of the VHL tumor suppressor and influences the behavior of hypoxic tumor cells...
  21. ncbi request reprint Regulation of angiogenesis by hypoxia and hypoxia-inducible factors
    Michele M Hickey
    Department of Cell and Molecular Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia 19104, USA
    Curr Top Dev Biol 76:217-57. 2006
    ..This chapter will provide an overview of current knowledge and highlight new insights into the importance of HIF and hypoxia in angiogenesis in both physiological and pathophysiological conditions...
  22. pmc mir-210: a sensor for hypoxic stress during tumorigenesis
    Lijoy K Mathew
    Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cell 35:737-8. 2009
    ..In this issue of Molecular Cell, Huang et al. (2009) demonstrate that hypoxia-inducible mir-210 acts as a rheostat for cellular adaptation and survival by inhibiting tumor initiation...
  23. pmc Reactive oxygen species and cellular oxygen sensing
    Timothy P Cash
    Howard Hughes Medical Institute, University of Pennsylvania, Pennsylvania, USA
    Free Radic Biol Med 43:1219-25. 2007
    ....
  24. ncbi request reprint The importance of PU.1 concentration in hematopoietic lineage commitment and maturation
    Richard Dahl
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA
    Blood Cells Mol Dis 31:229-33. 2003
    ..PU.1 activity is inhibited in some cases of acute myelogenous leukemia (AML), therefore, inhibition of PU.1 induced maturation may be a critical step in leukemogenesis...
  25. pmc HIF-dependent hematopoietic factors regulate the development of the embryonic vasculature
    Diana L Ramirez-Bergeron
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Dev Cell 11:81-92. 2006
    ..These results suggest that HIF coordinates early endothelial cell emergence and vessel development by promoting hematopoietic cell survival and paracrine growth factor production...
  26. pmc HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth
    Kelly L Covello
    Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 20:557-70. 2006
    ....
  27. pmc Decreased growth of Vhl-/- fibrosarcomas is associated with elevated levels of cyclin kinase inhibitors p21 and p27
    Fiona A Mack
    University of Pennsylvania School of Medicine, Abramson Family Cancer Research Institute, Philadelphia, PA 19104, USA
    Mol Cell Biol 25:4565-78. 2005
    ..These results demonstrate that a loss of pVHL can induce growth arrest in certain cells types, which suggests that additional genetic mutations are necessary for VHL-associated tumorigenesis...
  28. pmc Differential regulation of the transcriptional activities of hypoxia-inducible factor 1 alpha (HIF-1alpha) and HIF-2alpha in stem cells
    Cheng Jun Hu
    Howard Hughes Medical Institute and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Mol Cell Biol 26:3514-26. 2006
    ..HIF-2alpha repression may explain why patients with mutations in the VHL tumor suppressor gene display cancerous lesions in specific tissue types...
  29. pmc Hypoxia-inducible factors and the response to hypoxic stress
    Amar J Majmundar
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 40:294-309. 2010
    ..These transcription factors function in normal tissue homeostasis and impinge on critical aspects of disease progression and recovery. Insights from basic HIF biology are being translated into pharmaceuticals targeting the HIF pathway...
  30. pmc Hypoxia-inducible factors in stem cells and cancer
    Jolly Mazumdar
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    J Cell Mol Med 13:4319-28. 2009
    ..Direct molecular links have also been established between HIFs and critical cell signalling pathways such as cMyc and p53. These novel links suggest a new role for HIFs in stem cell and tumour regulation...
  31. pmc Hypoxia-inducible factors: central regulators of the tumor phenotype
    John D Gordan
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, PA, USA
    Curr Opin Genet Dev 17:71-7. 2007
    ..New targets and novel mechanisms of dysregulation place the HIFs in an ever more central role in tumor biology and have led to development of pharmacological inhibitors of their activity...
  32. pmc Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis
    Nicolas Skuli
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Blood 114:469-77. 2009
    ..Together, these data identify unique cell-autonomous functions for HIF-2alpha in vascular endothelial cells...
  33. pmc HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation
    John D Gordan
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cancer Cell 12:108-13. 2007
    ..However, acting in concert these transcription factors reprogram metabolism, protein synthesis, and cell cycle progression, to "fine tune" adaptive responses to hypoxic environments...
  34. pmc The impact of O2 availability on human cancer
    Jessica A Bertout
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Cancer 8:967-75. 2008
    ..The central role played by intra-tumoural hypoxia and HIF in these processes has made them attractive therapeutic targets in the treatment of multiple human malignancies...
  35. pmc Effects of 4E-BP1 expression on hypoxic cell cycle inhibition and tumor cell proliferation and survival
    Bryan C Barnhart
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 7:1441-9. 2008
    ..Thus, reduced expression of the negative regulator of eIF4E has significant effects on tumor development, and is associated with enhanced cell proliferation and survival...
  36. ncbi request reprint Targeted replacement of hypoxia-inducible factor-1alpha by a hypoxia-inducible factor-2alpha knock-in allele promotes tumor growth
    Kelly L Covello
    Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Cancer Res 65:2277-86. 2005
    ..These and other data indicate that HIF-2alpha promotes tumor growth more effectively than HIF-1alpha in multiple contexts...
  37. ncbi request reprint The bHLH/PAS factor MOP3 does not participate in hypoxia responses
    Karen D Cowden
    Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA
    Biochem Biophys Res Commun 290:1228-36. 2002
    ..5 embryos exhibit no angiogenic defects as shown for Arnt(-/-), Hif1alpha(-/-), and Hif2alpha(-/-) embryos. Therefore, by a variety of criteria, we show that MOP3 has little if any role in the regulation of hypoxia responses in vivo...
  38. ncbi request reprint Regulation of transcription and translation by hypoxia
    Liping Liu
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 3:492-7. 2004
    ....
  39. ncbi request reprint Enforced expression of Spi-B reverses T lineage commitment and blocks beta-selection
    Juliette M Lefebvre
    Immunobiology Working Group, Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    J Immunol 174:6184-94. 2005
    ....
  40. ncbi request reprint Regulation of macrophage and neutrophil cell fates by the PU.1:C/EBPalpha ratio and granulocyte colony-stimulating factor
    Richard Dahl
    Howard Hughes Medical Institute, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nat Immunol 4:1029-36. 2003
    ..1. Collectively, these results indicate that cytokines can promote cell fate decisions by altering the relative concentrations of lineage-determining transcriptional regulators...
  41. pmc Spi-B can functionally replace PU.1 in myeloid but not lymphoid development
    Richard Dahl
    Abramson Family Cancer Research Institute and Howard Hughes Medical Institute, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA
    EMBO J 21:2220-30. 2002
    ..These results demonstrate an important difference between PU.1 and Spi-B. Careful comparison of these Ets factors will delineate important functional domains of PU.1 involved in lymphocyte lineage commitment and/or maturation...
  42. ncbi request reprint Siah proteins, HIF prolyl hydroxylases, and the physiological response to hypoxia
    M Celeste Simon
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cell 117:851-3. 2004
    ..This preview examines cellular responses to O2 deprivation (hypoxia) and the complexity of the regulation of the HIF O2 sensing pathway in mammals...
  43. ncbi request reprint Identification of a c-myb attenuator-binding factor
    Jeffrey M Perkel
    Abramson Family Cancer Research Institute, University of Pennsylvania, Room 456, BRB 11 111, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Leuk Res 26:179-90. 2002
    ..We hypothesize that this factor may represent a member of the transcriptional attenuation complex...
  44. pmc Hypoxia inducible factor-2alpha: a critical mediator of aggressive tumor phenotypes
    Guoliang Qing
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Curr Opin Genet Dev 19:60-6. 2009
    ..Here we summarize recent studies on HIF-2alpha and discuss the potential mechanisms whereby it contributes to tumor aggressiveness...
  45. pmc HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma
    John D Gordan
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cancer Cell 14:435-46. 2008
    ..These reproducible distinctions in ccRCC behavior delineate HIF-alpha effects on c-Myc in vivo and suggest molecular criteria for selecting targeted therapies...
  46. pmc Metastasis and stem cell pathways
    Bryan C Barnhart
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA
    Cancer Metastasis Rev 26:261-71. 2007
    ..Hypoxia may contribute to tumor progression by specifically impacting these pathways in cancer stem cells...
  47. pmc Acute postnatal ablation of Hif-2alpha results in anemia
    Michaela Gruber
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 104:2301-6. 2007
    ....
  48. pmc The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis
    Julian J Lum
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 21:1037-49. 2007
    ..Together, these data suggest that HIF-1alpha contributes to the regulation of growth factor-stimulated glucose metabolism even in the absence of hypoxia...
  49. pmc Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro
    Yi Pan
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Mol Cell Biol 27:912-25. 2007
    ..Our results suggest that multiple mitochondrial products, including TCA cycle intermediates and reactive oxygen species, can coordinate PHD activity, HIF stabilization, and cellular responses to O(2) depletion...
  50. ncbi request reprint In vitro and in vivo models analyzing von Hippel-Lindau disease-specific mutations
    W Kimryn Rathmell
    Abramson Family Cancer Research Institute and the Department of Cell and Molecular Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 64:8595-603. 2004
    ..The ability to dissect specific VHL functions with missense mutations in a euploid model offers a novel opportunity to elucidate the activities of VHL as a tumor suppressor...
  51. pmc Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation
    Cheng Jun Hu
    Abramson Family Cancer Research Institute Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Mol Cell Biol 23:9361-74. 2003
    ..Importantly, HIF-1alpha (and not HIF-2alpha) stimulates glycolytic gene expression in both types of cells, clearly showing for the first time that HIF-1alpha and HIF-2alpha have unique targets...
  52. pmc Hypoxia-inducible factors as essential regulators of inflammation
    Hongxia Z Imtiyaz
    Abramson Family Cancer Research Institute, University of Pennsylvania, 438 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104 6160, USA
    Curr Top Microbiol Immunol 345:105-20. 2010
    ..We will also discuss how hypoxia and HIFs control properties of tumor-associated macrophages and their relationship to tumor formation and progression...
  53. ncbi request reprint Hypoxia-inducible factors, hypoxia, and tumor angiogenesis
    Michaela Gruber
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Curr Opin Hematol 13:169-74. 2006
    ..This review summarizes recent studies on hypoxia-inducible factor-alpha functions in development and tumorigenesis...
  54. ncbi request reprint Hypoxia, HIF and the placenta
    Benjamin H Fryer
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Cell Cycle 5:495-8. 2006
    ....
  55. pmc O2 regulates stem cells through Wnt/β-catenin signalling
    Jolly Mazumdar
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Nat Cell Biol 12:1007-13. 2010
    ..This decline correlates with reduced Wnt/β-catenin signalling in the subgranular zone. O2 availability, therefore, may have a direct role in stem cell regulation through HIF-1α modulation of Wnt/β-catenin signalling...
  56. ncbi request reprint Tumor suppression through angiogenesis inhibition
    Andrew M Arsham
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, USA
    Methods Mol Biol 223:249-70. 2003
  57. pmc Hypoxia-induced energy stress regulates mRNA translation and cell growth
    Liping Liu
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
    Mol Cell 21:521-31. 2006
    ..Together, eIF2alpha, eEF2, and mTOR inhibition represent important HIF-independent mechanisms of energy conservation that promote survival under low O2 conditions...
  58. pmc Acute anemia elicits cognitive dysfunction and evidence of cerebral cellular hypoxia in older rats with systemic hypertension
    Min Li
    Department of Anesthesiology and Critical Care, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Anesthesiology 113:845-58. 2010
    ..Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia...
  59. pmc Hypoxia-inducible factor 2alpha regulates macrophage function in mouse models of acute and tumor inflammation
    Hongxia Z Imtiyaz
    Abramson Family Cancer Research Institute, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6160, USA
    J Clin Invest 120:2699-714. 2010
    ..Collectively, our data identify HIF-2alpha as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer...
  60. ncbi request reprint An abundant erythroid protein that stabilizes free alpha-haemoglobin
    Anthony J Kihm
    The Children s Hospital of Philadelphia, Division of Hematology and the University of Pennsylvania, Philadelphia, Pennsylvania 19104 616, USA
    Nature 417:758-63. 2002
    ..Accordingly, AHSP gene dosage is predicted to modulate pathological states of alpha-haemoglobin excess, such as beta-thalassaemia...
  61. pmc Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth
    Fiona A Mack
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cancer Cell 3:75-88. 2003
    ..We further demonstrate that loss of murine Vhl does not promote teratocarcinoma growth, indicating that other genetic changes must occur to facilitate Vhl-mediated tumorigenesis...
  62. ncbi request reprint Ribosomal stress couples the unfolded protein response to p53-dependent cell cycle arrest
    Fang Zhang
    Leonard and Madlyn Abramson Family Cancer Research Institute and Howard Hughes Medical Institute, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 281:30036-45. 2006
    ..Our data demonstrate that ribosomal subunit:Hdm2 association couples the unfolded protein response to p53-dependent cell cycle arrest...
  63. ncbi request reprint Coming up for air: HIF-1 and mitochondrial oxygen consumption
    M Celeste Simon
    Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cell Metab 3:150-1. 2006
    ..2006) demonstrate that HIF-1 also influences mitochondrial function, suppressing both the TCA cycle and respiration by inducing pyruvate dehydrogenase kinase 1 (PDK1). PDK1 regulation in hypoxic cells promotes cell survival...
  64. pmc Hypoxia-mediated selective mRNA translation by an internal ribosome entry site-independent mechanism
    Regina M Young
    Abramson Family Cancer Research Institute, Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, and Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia Pennsylvania 19104, USA
    J Biol Chem 283:16309-19. 2008
    ..In addition, our data suggest that cyclin-dependent kinase inhibitor p57(Kip2) and vascular endothelial growth factor mRNAs are selectively translated by an IRES-independent mechanism under hypoxic stress...
  65. ncbi request reprint Mxi1 is induced by hypoxia in a HIF-1-dependent manner and protects cells from c-Myc-induced apoptosis
    Paul G Corn
    University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Cancer Biol Ther 4:1285-94. 2005
    ..The results suggest a coordinated mechanism for opposing c-Myc signaling during hypoxia that is mediated by a reduction in c-Myc levels, the induction of Mxi1, and a dominant effect of HIF-1 transcriptional activity...
  66. ncbi request reprint Truncation of c-fes via gene targeting results in embryonic lethality and hyperproliferation of hematopoietic cells
    Renee Hackenmiller
    Committee on Genetics, University of Chicago, Chicago, Illinois 60637, USA
    Dev Biol 245:255-69. 2002
    ..5 with embryos exhibiting pleiotropic defects, the most striking being cardiovascular abnormalities. These results establish that c-fes is an important regulator of myeloid cell proliferation and embryonic development...
  67. ncbi request reprint Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase
    Mary A Selak
    Apoptosis and Tumour Physiology Laboratory, Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Switchback Road, Glasgow G61 1BD, United Kingdom
    Cancer Cell 7:77-85. 2005
    ..These results suggest a mechanistic link between SDH mutations and HIF-1alpha induction, providing an explanation for the highly vascular tumors that develop in the absence of VHL mutations...
  68. ncbi request reprint Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
    Robert D Guzy
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    Cell Metab 1:401-8. 2005
    ..These results demonstrate that mitochondria function as O(2) sensors and signal hypoxic HIF-1 alpha and HIF-2 alpha stabilization by releasing ROS to the cytosol...
  69. ncbi request reprint Hypoxia-inducible factor-dependent histone deacetylase activity determines stem cell fate in the placenta
    Emin Maltepe
    Department of Pediatrics and Molecular Medicine Program, University of California, Parnassus Avenue, San Francisco, CA 94143, USA
    Development 132:3393-403. 2005
    ..Thus, the HIFs play important roles in modulating the developmental plasticity of stem cells by integrating physiological, transcriptional and epigenetic inputs...
  70. ncbi request reprint PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR
    Rosa Bernardi
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
    Nature 442:779-85. 2006
    ..Thus, our findings identify PML as a novel suppressor of mTOR and neoangiogenesis...
  71. ncbi request reprint A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets
    Andrew M Arsham
    Committee on Genetics, University of Chicago, Chicago, Illinois 60615, USA
    J Biol Chem 278:29655-60. 2003
    ..These data demonstrate a new mode of regulation of the mTOR pathway and position this pathway as a powerful point of control by O2 of cellular metabolism and energetics...
  72. ncbi request reprint Phosphatidylinositol 3-kinase/Akt signaling is neither required for hypoxic stabilization of HIF-1 alpha nor sufficient for HIF-1-dependent target gene transcription
    Andrew M Arsham
    Committee on Genetics, University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 277:15162-70. 2002
    ..Therefore, the PI3K/Akt pathway is not necessary for hypoxic induction of HIF-1 subunits or activity, and constitutively active Akt is not itself sufficient to induce HIF-1 activity...
  73. pmc The transcriptional repressor GFI-1 antagonizes PU.1 activity through protein-protein interaction
    Richard Dahl
    Department of Internal Medicine, Health Sciences Center, University of New Mexico, Albuquerque, New Mexico 87131, USA
    J Biol Chem 282:6473-83. 2007
    ..Our data demonstrate that GFI-1 represses PU.1 activity and that lack of this repression in Gfi-1(-/-) myeloid cells contributes to the observed mixed lineage phenotype...
  74. pmc The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease
    Amato J Giaccia
    Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, USA
    Genes Dev 18:2183-94. 2004
    ..It will also comment on future directions for this exciting field...
  75. pmc pVHL function is essential for endothelial extracellular matrix deposition
    Nan Tang
    Molecular Biology Section, MC 0377, Division of Biological Sciences, University of California San Diego, La Jolla, California 92093 0377, USA
    Mol Cell Biol 26:2519-30. 2006
    ....
  76. ncbi request reprint Spi-1 and Spi-B control the expression of the Grap2 gene in B cells
    Lee Ann Garrett-Sinha
    Department of Biochemistry, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA
    Gene 353:134-46. 2005
    ....
  77. ncbi request reprint The transcription factor Spi-B is not required for somatic hypermutation
    Nayun Kim
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
    Mol Immunol 39:577-83. 2003
    ..The mutations causing the change to Phe are transitions which are favored by the SHM process over transversions. Clearly, Phe-81 must arise relatively frequently, but is not selected in Spi-B wildtype mice...
  78. ncbi request reprint HIF transcription factor expression and induction of hypoxic response genes in a retroperitoneal angiosarcoma
    W Kimryn Rathmell
    Division of Hematology Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, USA
    Anticancer Res 24:167-9. 2004
    ..Disordered regulation of the hypoxic response pathway can result in the expression of factors such as VEGF and erythropoietin, which may promote autocrine tumor growth in angiosarcoma...
  79. ncbi request reprint c-Myc sensitization to oxygen deprivation-induced cell death is dependent on Bax/Bak, but is independent of p53 and hypoxia-inducible factor-1
    Joslyn K Brunelle
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611 3010, USA
    J Biol Chem 279:4305-12. 2004
    ..Thus, oxygen deprivation-induced cell death in fibroblasts with deregulated expression of c-Myc is independent of p53 or HIF-1 status, but is dependent on the Bcl-2 family member Bax or Bak to initiate mitochondrial dependent cell death...
  80. ncbi request reprint Akt and hypoxia-inducible factor-1 independently enhance tumor growth and angiogenesis
    Andrew M Arsham
    Committee on Genetics, University of Chicago, Chicago, Illinois, USA
    Cancer Res 64:3500-7. 2004
    ..Thus, Akt has potent, HIF-1-independent oncogenic and angiogenic activities...
  81. ncbi request reprint Molecular basis of Stat1 and PU.1 cooperation in cytokine-induced Fcgamma receptor I promoter activation
    Saara Aittomaki
    Institute of Medical Technology, University of Tampere, 33014 Tampere, Finland
    Int Immunol 16:265-74. 2004
    ..These results define functional cooperativity between PU.1 and Stat1 in FcgammaRI promoter activation where PU.1 serves as an amplifier and bridging factor with the basal transcription machinery...
  82. pmc Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation
    Karen D Cowden Dahl
    The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, Belgium
    Mol Cell Biol 25:10479-91. 2005
    ..This novel genetic approach provides new insights into the role of O2 tension in the development of life-threatening pregnancy-related diseases such as preeclampsia...

Research Grants14

  1. HIF-2alpha, hypoxic gene regulation, and angiogenesis
    M Simon; Fiscal Year: 2007
    ..The overall goal of our studies is to elucidate how HIF-1alpha and HIF-2alpha differentially regulate hypoxic gene induction and how this contributes to embryogenesis, angiogenesis, and neoplastic disease. ..
  2. ARNT PROTEIN FUNCTION IN ANGIOGENESIS AND HEMATOPOIESIS
    M Simon; Fiscal Year: 2000
    ..At a basic level, they will provide important information oon hypoxia-induced transcriptional regulation that complements our rapidly expanding understanding of receptor/ ligand signalling in angiogenesis and hematopoiesis. ..
  3. HIF- 2ALPHA, Hypoxic Gene Regulation, and Angiogenesis
    M Simon; Fiscal Year: 2009
    ..This project will provide fundamental insights into how these factors regulate blood vessel growth in diseases and identify new therapeutic targets to treat cancer, stroke, and heart attack patients. ..
  4. HIF-2alpha, hypoxic gene regulation, and angiogenesis
    M Simon; Fiscal Year: 2006
    ..The overall goal of our studies is to elucidate how HIF-1alpha and HIF-2alpha differentially regulate hypoxic gene induction and how this contributes to embryogenesis, angiogenesis, and neoplastic disease. ..
  5. Hypoxia and Development, Physiology and Disease
    M Simon; Fiscal Year: 2005
    ..The goal of this meeting is to bring together hypoxia researchers studying yeast, fly, worm, mammals, development, tissue homeostasis, disease, and drug discovery. ..
  6. HIF-2alpha, hypoxic gene regulation, and angiogenesis
    M Simon; Fiscal Year: 2005
    ..The overall goal of our studies is to elucidate how HIF-1alpha and HIF-2alpha differentially regulate hypoxic gene induction and how this contributes to embryogenesis, angiogenesis, and neoplastic disease. ..
  7. HIF-2alpha, hypoxic gene regulation, and angiogenesis
    M Simon; Fiscal Year: 2004
    ..The overall goal of our studies is to elucidate how HIF-1alpha and HIF-2alpha differentially regulate hypoxic gene induction and how this contributes to embryogenesis, angiogenesis, and neoplastic disease. ..
  8. ARNT PROTEIN FUNCTION IN ANGIOGENESIS AND HEMATOPOIESIS
    M Simon; Fiscal Year: 2003
    ..At a basic level, they will provide important information oon hypoxia-induced transcriptional regulation that complements our rapidly expanding understanding of receptor/ ligand signalling in angiogenesis and hematopoiesis. ..
  9. ARNT PROTEIN FUNCTION IN ANGIOGENESIS AND HEMATOPOIESIS
    M Simon; Fiscal Year: 2002
    ..At a basic level, they will provide important information oon hypoxia-induced transcriptional regulation that complements our rapidly expanding understanding of receptor/ ligand signalling in angiogenesis and hematopoiesis. ..
  10. PU1 AND SPI B AND HEMATOPOIETIC DEVELOPMENT
    M Simon; Fiscal Year: 2002
    ..1+/- Spi-B+/- lymphocytes. These studies will have important implications for our understanding of how related transcription factors promoter different aspects of blood cell maturation. ..
  11. PU1 AND SPI B AND HEMATOPOIETIC DEVELOPMENT
    M Simon; Fiscal Year: 2001
    ..1+/- Spi-B+/- lymphocytes. These studies will have important implications for our understanding of how related transcription factors promoter different aspects of blood cell maturation. ..
  12. ARNT PROTEIN FUNCTION IN ANGIOGENESIS AND HEMATOPOIESIS
    M Simon; Fiscal Year: 2001
    ..At a basic level, they will provide important information oon hypoxia-induced transcriptional regulation that complements our rapidly expanding understanding of receptor/ ligand signalling in angiogenesis and hematopoiesis. ..
  13. HIF- 2ALPHA, Hypoxic Gene Regulation, and Angiogenesis
    M Celeste Simon; Fiscal Year: 2010
    ..This project will provide fundamental insights into how these factors regulate blood vessel growth in diseases and identify new therapeutic targets to treat cancer, stroke, and heart attack patients. ..