Research Topics
Genomes and Genes | Gregg SemenzaSummaryAffiliation: Johns Hopkins University Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Involvement of hypoxia-inducible factor 1 in human cancerGregg L Semenza
Institute of Genetic Medicine, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Intern Med 41:79-83. 2002..Fourth, in addition to intratumoral hypoxia, genetic alterations in tumor suppressor genes and oncogenes induce HIF-1 activity...
Molecular mechanisms mediating metastasis of hypoxic breast cancer cellsGregg L Semenza
Vascular Program, Institute for Cell Engineering, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Trends Mol Med 18:534-43. 2012..Digoxin, a drug that inhibits HIF-1 activity, blocks primary tumor growth, vascularization, invasion, and metastasis in ex vivo and in vivo assays...
The role of hypoxia-inducible factors in oxygen sensing by the carotid bodyGregg L Semenza
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Adv Exp Med Biol 758:1-5. 2012..Thus, IH disrupts the balance between HIF-1-dependent pro-oxidant and HIF-2-dependent anti-oxidant activities, and this loss of redox homeostasis underlies the pathogenesis of autonomic morbidities associated with IH...- Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapyGregg L Semenza
Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Trends Pharmacol Sci 33:207-14. 2012.... - Hypoxia-inducible factors in physiology and medicineGregg L Semenza
Vascular Program, Institute for Cell Engineering, Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry, McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Cell 148:399-408. 2012.... - Life with oxygenGregg L Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, USA
Science 318:62-4. 2007..Pharmacologic agents that activate or inhibit the hypoxia signal transduction pathway may be useful therapies for ischemic and neoplastic disorders, respectively, which are the major causes of mortality in industrialized societies... - New insights into nNOS regulation of vascular homeostasisGregg L Semenza
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
J Clin Invest 115:2976-8. 2005.... - Pulmonary vascular responses to chronic hypoxia mediated by hypoxia-inducible factor 1Gregg L Semenza
Program in Vascular Cell Engineering, Johns Hopkins University School of Medicine, 733 N Broadway, Suite 671, Baltimore, MD 21205, USA
Proc Am Thorac Soc 2:68-70. 2005..HIF-1 plays critical roles both during development and in response to physiologic and pathophysiologic stimuli in the adult. Here, the involvement of HIF-1 in lung pathophysiology will be discussed... - Regulation of cancer cell metabolism by hypoxia-inducible factor 1Gregg L Semenza
Institute for Cell Engineering, Department of Pediatrics, McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, United States
Semin Cancer Biol 19:12-6. 2009..Targeting HIF-1 or metabolic enzymes encoded by HIF-1 target genes may represent a novel therapeutic approach to cancer... - Regulation of oxygen homeostasis by hypoxia-inducible factor 1Gregg L Semenza
Vascular Program, Institute for Cell Engineering, McKusick Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA
Physiology (Bethesda) 24:97-106. 2009..HIF-1 also mediates maladaptive responses to chronic continuous and intermittent hypoxia, which underlie the development of pulmonary and systemic hypertension, respectively... - Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesisGregg L Semenza
Vascular Program, Institute for Cell Engineering, McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA
Blood 114:2015-9. 2009..Intense efforts are under way to identify small molecule hydroxylase inhibitors that can be administered chronically to selectively induce erythropoiesis without undesirable side effects... - Regulation of tissue perfusion in mammals by hypoxia-inducible factor 1Gregg L Semenza
Vascular Biology Program and Institute for Cell Engineering, Departments of Pediatrics, Medicine, Oncology and Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Exp Physiol 92:988-91. 2007..Administration of viral vectors encoding constitutively active forms of the HIF-1alpha subunit results in increased tissue perfusion in animal models of ischaemic cardiovascular disease... - HIF-1 inhibitors for cancer therapy: from gene expression to drug discoveryG L Semenza
The Johns Hopkins University Schoolof Medicine, Baltimore, MD 21205, USA
Curr Pharm Des 15:3839-43. 2009.... - Vascular responses to hypoxia and ischemiaGregg L Semenza
Institute for Cell Engineering, Departments of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Arterioscler Thromb Vasc Biol 30:648-52. 2010..Impairment of HIF-1-dependent responses to hypoxia is a major factor contributing to the impaired vascular responses to ischemia that are associated with aging and diabetes... - Hydroxylation of HIF-1: oxygen sensing at the molecular levelGregg L Semenza
Program in Vascular Cell Engineering, Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Physiology (Bethesda) 19:176-82. 2004..The discovery of the transcription factor HIF-1 has led to the identification of protein hydroxylation as a mechanism by which changes in PO2 are transduced to effect changes in gene expression... - Regulation of vascularization by hypoxia-inducible factor 1Gregg L Semenza
Vascular Program, Institute for Cell Engineering McKusick Nathans Institute of Genetic Medicine, Baltimore, Maryland 21205, USA
Ann N Y Acad Sci 1177:2-8. 2009.... - HIF-1: upstream and downstream of cancer metabolismGregg L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, United States
Curr Opin Genet Dev 20:51-6. 2010..Many metabolic abnormalities in cancer cells increase HIF-1 activity. As a result, a feed-forward mechanism can be activated that drives HIF-1 activation and may promote tumor progression... - Does loss of CD151 expression promote the metastasis of hypoxic colon cancer cells?Gregg L Semenza
Vascular Program, Institute for Cell Engineering, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Clin Cancer Res 14:7969-70. 2008..In hypoxic colon cancer cells, hypoxia-inducible factor 1 inhibits the expression of CD151, a cell surface molecule that normally tethers epithelial cells to the basement membrane, which may promote metastasis... - Involvement of hypoxia-inducible factor 1 in pulmonary pathophysiologyGregg L Semenza
The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Chest 128:592S-594S. 2005..These studies implicate HIF-1 in pathophysiologic alterations of both smooth muscle and endothelial cell biology in patients with pulmonary hypertension... - Vasculogenesis, angiogenesis, and arteriogenesis: mechanisms of blood vessel formation and remodelingGregg L Semenza
Vascular Biology Program, Institute for Cell Engineering Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Cell Biochem 102:840-7. 2007.... - Hypoxia-inducible factor 1 (HIF-1) pathwayGregg L Semenza
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, USA
Sci STKE 2007:cm8. 2007..A growing number of proteins and small molecules have been identified that regulate HIF-1 activity by modulating the physical or functional interaction of PHD2, VHL, FIH-1, RACK1, or HSP90 with HIF-1alpha... - Evaluation of HIF-1 inhibitors as anticancer agentsGregg L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, 733 North Broadway, Suite 671, Baltimore, MD 21205, USA
Drug Discov Today 12:853-9. 2007..Determining which combination of drugs to administer to any given patient remains a major obstacle to improving cancer treatment outcomes... - HIF-1-dependent respiratory, cardiovascular, and redox responses to chronic intermittent hypoxiaGregg L Semenza
Vascular Biology Program, Institute for Cell Engineering, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Antioxid Redox Signal 9:1391-6. 2007.... - Hypoxia and human disease-and the Journal of Molecular MedicineG L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD, 21205, USA
J Mol Med 85:1293-4. 2007 - Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1Gregg L Semenza
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Biochem J 405:1-9. 2007.... - HIF-1 mediates the Warburg effect in clear cell renal carcinomaGregg L Semenza
Institute for Cell Engineering, Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology, and McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Bioenerg Biomembr 39:231-4. 2007..These findings delineate for the first time the molecular mechanisms underlying the Warburg effect in a human cancer... - Mitochondrial autophagy: life and breath of the cellGregg L Semenza
Vascular Program, Institute for Cell Engineering, Department of Pediatrics, McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Autophagy 4:534-6. 2008..These studies indicate that mitochondrial autophagy represents an adaptive metabolic response to hypoxia that is necessary to maintain redox homeostasis and cell survival... - Hypoxia and cancerGregg L Semenza
Vascular Biology Program, Institute for Cell Engineering, The John Hopkins University School of Medicine, Baltimore, MD 21205, USA
Cancer Metastasis Rev 26:223-4. 2007 - O2 sensing: only skin deep?Gregg L Semenza
Vascular Program, Institute for Cell Engineering Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology, Baltimore, MD 21205, USA
Cell 133:206-8. 2008.... - Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia-inducible factor 1Gregg L Semenza
Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Exp Physiol 91:803-6. 2006.... - Hypoxia-inducible factor 1 and cancer pathogenesisGregg L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
IUBMB Life 60:591-7. 2008..Proof of principle studies in mouse models suggests that inhibition of HIF-1 activity may have therapeutic effects, especially in combination with other anticancer drugs... - Tumor metabolism: cancer cells give and take lactateGregg L Semenza
Vascular Program, Institute for Cell Engineering, Department of Pediatrics, John Hopkins University School of Medicine, Baltimore, Maryland, USA
J Clin Invest 118:3835-7. 2008..MCT1 expression was detected exclusively in nonhypoxic regions of human cancer biopsy samples, and in combination, these data suggest that MCT1 inhibition holds potential as a novel cancer therapy... - Intratumoral hypoxia, radiation resistance, and HIF-1Gregg L Semenza
Program in Vascular Cell Engineering, The Johns Hopkins University School of Medicine, 733 North Broadway, Suite 671, Baltimore, MD 21205, USA
Cancer Cell 5:405-6. 2004..In this issue of Cancer Cell, now provide evidence that radiation induces HIF-1-mediated expression of VEGF and bFGF in tumor cells, which promotes endothelial cell survival... - Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeuticsG L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Oncogene 29:625-34. 2010.... - Regulation of cardiovascular development and physiology by hypoxia-inducible factor 1G L Semenza
Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Ann N Y Acad Sci 874:262-8. 1999.... - Development of novel therapeutic strategies that target HIF-1Gregg L Semenza
Vascular Biology Program of the Johns Hopkins Institute for Cell Engineering, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, USA
Expert Opin Ther Targets 10:267-80. 2006..Several novel compounds with anticancer activity have been shown to inhibit HIF-1 and may be useful as components of individualised multidrug therapeutic regimens chosen based on molecular analyses of tumour biopsies... - Oxygen-regulated transcription factors and their role in pulmonary diseaseG L Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Respir Res 1:159-62. 2000..Angiotensin II induces HIF-1 expression and hypertrophy of pulmonary arterial smooth muscle cells. HIF-1 might therefore have multiple roles in the pathogenesis of pulmonary vascular remodeling... - HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleusG L Semenza
McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Cell 107:1-3. 2001..A molecular basis for O(2)-regulated expression of the HIF-1 alpha subunit has now been determined, providing a mechanism for changes in gene expression in response to changes in cellular oxygenation... - Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiologyG L Semenza
Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Johns Hopkins Hospital, CMSC 1004, 600 North Wolfe Street, Baltimore, MD 21287 3914, USA
Trends Mol Med 7:345-50. 2001..Modulation of HIF-1 activity by genetic or pharmacological means could provide a novel therapeutic approach to these common causes of mortality... - Hypoxia-inducible factor 1: control of oxygen homeostasis in health and diseaseG L Semenza
Institute of Genetic Medicine and Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Pediatr Res 49:614-7. 2001..HIF-1 may also mediate the protective response to cerebral ischemia known as late-phase preconditioning... - HIF-1 and mechanisms of hypoxia sensingG L Semenza
Johns Hopkins Hospital, CMSC 1004, 600 North Wolfe Street, Baltimore, Maryland 21287 3914, USA
Curr Opin Cell Biol 13:167-71. 2001..The signal transduction pathway remains enigmatic, but involves generation of reactive oxygen species. Nitric oxide induces HIF-1 alpha under non-hypoxic conditions but inhibits hypoxia-induced HIF-1 alpha expression... - HIF-1: using two hands to flip the angiogenic switchG L Semenza
Institute of Genetic Medicine, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Cancer Metastasis Rev 19:59-65. 2000.... - HIF-1 and human disease: one highly involved factorG L Semenza
Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914 USA
Genes Dev 14:1983-91. 2000 - Hypoxia, clonal selection, and the role of HIF-1 in tumor progressionG L Semenza
Institute of Genetic Medicine, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Crit Rev Biochem Mol Biol 35:71-103. 2000.... - HIF-1: mediator of physiological and pathophysiological responses to hypoxiaG L Semenza
Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287 3914, USA
J Appl Physiol 88:1474-80. 2000..Genetic or pharmacological modulation of HIF-1 activity in vivo may represent a novel therapeutic approach to these disorders... - Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1G L Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Annu Rev Cell Dev Biol 15:551-78. 1999..HIF-1 thus appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology... - Expression of hypoxia-inducible factor 1: mechanisms and consequencesG L Semenza
The Johns Hopkins School of Medicine, Baltimore, MD 21287 3914, USA
Biochem Pharmacol 59:47-53. 2000..Pharmacologic manipulation of HIF-1 levels may provide a novel therapeutic approach to diseases that represent the most common causes of mortality in Western society, including cancer, chronic lung disease, and myocardial ischemia... - HIF-1 and tumor progression: pathophysiology and therapeuticsGregg L Semenza
Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, 600 N Wolfe Street, CMSC 1004, Baltimore, MD 21287 3914, USA
Trends Mol Med 8:S62-7. 2002..Increased HIF-1 activity promotes tumor progression, and inhibition of HIF-1 could represent a novel approach to cancer therapy... - Hypoxia. Cross talk between oxygen sensing and the cell cycle machineryGregg L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Am J Physiol Cell Physiol 301:C550-2. 2011..Thus HIF and MCM proteins act in a mutually antagonistic manner, providing a novel molecular mechanism for homeostatic regulation of cell proliferation based on the relative levels of these proteins... - Physiology meets biophysics: visualizing the interaction of hypoxia-inducible factor 1 alpha with p300 and CBPGregg L Semenza
McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-3914, USA
Proc Natl Acad Sci U S A 99:11570-2. 2002 - Signal transduction to hypoxia-inducible factor 1Gregg Semenza
Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 1004, Baltimore, MD 21287 3914, USA
Biochem Pharmacol 64:993-8. 2002.... - Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioningGregg L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Biochim Biophys Acta 1813:1263-8. 2011..HIF-1-dependent regulation of mitochondrial metabolism may also contribute to the protective effects of ischemic preconditioning. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection... - Angiogenesis in ischemic and neoplastic disordersGregg L Semenza
McKusick Nathans Institute of Genetic Medicine and the Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Annu Rev Med 54:17-28. 2003..Novel therapeutic approaches that involve stimulating angiogenesis in ischemic tissue and inhibiting angiogenesis in neoplastic tissue are currently being evaluated in clinical trials... - Targeting HIF-1 for cancer therapyGregg L Semenza
McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Nat Rev Cancer 3:721-32. 2003..In preclinical studies, inhibition of HIF-1 activity has marked effects on tumour growth. Efforts are underway to identify inhibitors of HIF-1 and to test their efficacy as anticancer therapeutics... - Oxygen homeostasisGregg L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MA 21205, USA
Wiley Interdiscip Rev Syst Biol Med 2:336-61. 2010..Recent studies have elucidated complex mechanisms by which HIF-1 activity is regulated and by which HIF-1 regulates gene expression, with profound consequences for prenatal development, postnatal physiology, and disease pathogenesis... - Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cellsRyo Fukuda
McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
J Biol Chem 277:38205-11. 2002..Involvement of the MAP kinase pathway represents a novel mechanism for the induction of HIF-1 alpha protein expression in human cancer cells... - Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1Ryo Fukuda
McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Cancer Res 63:2330-4. 2003..Thus, the activity of multiple signal transduction pathways is required for the HIF-1-mediated induction of VEGF expression in colon cancer cells exposed to PGE(2)... - OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alphaJin Hyen Baek
Institute for Cell Engineering, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Cell 17:503-12. 2005..These data indicate that OS-9 is an essential component of a multiprotein complex that regulates HIF-1alpha levels in an O2-dependent manner... - Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodellingSergio Rey
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 N Broadway, Baltimore, MD 21205, USA
Cardiovasc Res 86:236-42. 2010..This review will focus on the pivotal role of HIF-1 in vascular homeostasis, the involvement of HIF-1 in vascular diseases, and recent advances in targeting HIF-1 for therapy in preclinical models... - Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1Jung whan Kim
Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Mol Cell Biol 27:7381-93. 2007.... - Calcineurin promotes hypoxia-inducible factor 1alpha expression by dephosphorylating RACK1 and blocking RACK1 dimerizationYe V Liu
Vascular Program, Institute for Cell Engineering, Department of Pharmacology and Molecular Sciences, Mass Spectronomy Proteomics Facility, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Biol Chem 282:37064-73. 2007..These results indicate that intracellular calcium levels can regulate HIF-1alpha expression by modulating calcineurin activity and RACK1 dimerization... - O2-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1Gregg L Semenza
Johns Hopkins University School of Medicine, McKusick-Nathans Institute of Genetic Medicine, Program in Vascular Cell Engineering, Institute for Cell Engineering, Baltimore, MD 21205, USA
J Appl Physiol 96:1173-7; discussion 1170-2. 2004..Thus HIF-1 mediates critical physiological responses to hypoxia, and the elucidation of these homeostatic mechanisms may lead to novel therapies for the most common causes of mortality in the US population... - Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1Brian D Kelly
Program in Vascular Cell Engineering, Institute for Cell Engineering, Baltimore, MD, USA
Circ Res 93:1074-81. 2003.... - Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1Balaji Krishnamachary
McKusick-Nathans Institute of Genetic Medicine and Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA
Cancer Res 63:1138-43. 2003..These results provide a molecular basis for promotion of the invasive cancer phenotype by hypoxia and/or HIF-1 alpha overexpression... - HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activityHuafeng Zhang
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Cancer Cell 11:407-20. 2007..We demonstrate that transcription of the gene encoding the coactivator PGC-1beta is C-MYC dependent and that loss of PGC-1beta expression is a major factor contributing to reduced respiration in VHL-deficient renal carcinoma cells... - HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxiaJung whan Kim
Graduate Program of Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cell Metab 3:177-85. 2006..These studies reveal a hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production... - Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cellsKangAe Lee
Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 106:2353-8. 2009..These results provide a molecular basis for the antiangiogenic effect of anthracycline therapy and have important implications for refining the use of these drugs to treat human cancer more effectively... - Spermidine/spermine N(1)-acetyltransferase-1 binds to hypoxia-inducible factor-1alpha (HIF-1alpha) and RACK1 and promotes ubiquitination and degradation of HIF-1alphaJin H Baek
Vascular Program, Institute for Cell Engineering, The Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology
J Biol Chem 282:33358-66. 2007..However, in contrast to SSAT2, SSAT1 acts by stabilizing the interaction of HIF-1alpha with RACK1. Thus, the paralogs SSAT1 and SSAT2 play complementary roles in promoting O(2)-independent and O(2)-dependent degradation of HIF-1alpha... - Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1BBalaji Krishnamachary
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cancer Res 66:2725-31. 2006..Thus, HIF-1 contributes to the epithelial-mesenchymal transition in VHL-null RCC by indirect repression of E-cadherin... - Age-dependent impairment of HIF-1alpha expression in diabetic mice: Correction with electroporation-facilitated gene therapy increases wound healing, angiogenesis, and circulating angiogenic cellsLixin Liu
Section of Surgical Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
J Cell Physiol 217:319-27. 2008..Thus, HIF-1alpha gene therapy corrects the age-dependent impairment of HIF-1alpha expression, angiogenic cytokine expression, and CACs that contribute to the age-dependent impairment of wound healing in db/db mice... - Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progressionAnne Le
Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 107:2037-42. 2010.... - Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularizationKangAe Lee
Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 106:17910-5. 2009..These results provide proof of principle that small molecules can inhibit dimerization of HIF-1 and have potent inhibitory effects on tumor growth and vascularization... - The expanding universe of hypoxiaHuafeng Zhang
Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Mol Med (Berl) 86:739-46. 2008..In this meeting report, we summarize major developments in the field that were presented at the 2008 Keystone Symposium on Cellular, Physiological, and Pathogenic Responses to Hypoxia... - HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cellsRyo Fukuda
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Cell 129:111-22. 2007..Thus, mammalian cells respond to hypoxia by altering COX subunit composition, as previously observed in yeast, but by a completely different molecular mechanism... - Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxiaHuafeng Zhang
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 283:10892-903. 2008.... - Spermidine/spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1alphaJin Hyen Baek
Vascular Biology Program, Institute for Cell Engineering, Department of Pediatrics, and McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 282:23572-80. 2007..Multivalent interactions by SSAT2 provide a mechanism to ensure efficient complex formation, which is necessary for the extremely rapid ubiquitination and degradation of HIF-1alpha that is observed in oxygenated cells... - Functional analysis of the role of hypoxia-inducible factor 1 in the pathogenesis of hypoxic pulmonary hypertensionLarissa A Shimoda
Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkinds University School of Medicine, Baltimore, Maryland 21224, USA
Methods Enzymol 381:121-9. 2004 - Effects of aging and hypoxia-inducible factor-1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemiaMarta Bosch-Marce
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Circ Res 101:1310-8. 2007..These results indicate that HIF-1 activity is necessary and sufficient for the mobilization of angiogenic cells and that HIF-1alpha gene therapy can counteract the pathological effects of aging in a mouse model of limb ischemia... - Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1Dominador J Manalo
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Blood 105:659-69. 2005.... - Hypoxia-inducible factor 1alpha polymorphism and coronary collaterals in patients with ischemic heart diseaseJon R Resar
Division of Cardiology, The Johns Hopkins University School of Medicine, Blalock 524, 600 North Wolfe St, Baltimore, MD 21287, USA
Chest 128:787-91. 2005..Hypoxia inducible factor 1 (HIF-1), a transcriptional activator that functions as a master regulator of oxygen homeostasis, is one possible genetic factor that could play an important role in modulating collateral development... - PTEN activity is modulated during ischemia and reperfusion: involvement in the induction and decay of preconditioningZheqing Cai
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Circ Res 97:1351-9. 2005..Perfusion of H2(O2) was sufficient to induce Akt activation. Thus, loss of PTEN activity leads to induction of IPC and feedback mechanisms designed to ensure that Akt activation is transient are responsible for decay of IPC... - Proceedings of the Oxygen Homeostasis/Hypoxia MeetingBennett Kaufman
TRI Inc, Rockville, Maryland, USA
Cancer Res 64:3350-6. 2004 - Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injuryZheqing Cai
McKusick-Nathans Institute of Genetic Medicine, Baltimore, MD, USA
Circulation 108:79-85. 2003..Cardiac protection induced by intermittent hypoxia is critically dependent on Hif1a gene dosage. Our data suggest that additional studies to evaluate therapeutic applications of EPO administration are warranted... - Analysis of hypoxia-inducible factor 1alpha expression and its effects on invasion and metastasisBalaji Krishnamachary
Vascular Biology Program, Institute for Cell Engineering, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Methods Enzymol 435:347-54. 2007..Here, we describe methods for immunohistochemical detection of HIF-1alpha in tumor biopsy sections and ex vivo assays for analyzing the effects of hypoxia and HIF-1 on cancer cell invasiveness and cell-cell adhesion... - Partial rescue of defects in Cited2-deficient embryos by HIF-1alpha heterozygosityBing Xu
Department of Pharmacology and Cancer Center, Case Western Reserve University, School of Medicine, W319, Cleveland, OH 44106, USA
Dev Biol 301:130-40. 2007..These findings suggest that a precise level of HIF-1 transcriptional activity critical for normal development is triggered by differential hypoxia and regulated through feedback inhibition by Cited2... - Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAPK and phosphatidylinositol 3-kinase signalingKenji Kasuno
Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka, Japan 563 0053
J Biol Chem 279:2550-8. 2004..We conclude that the NO donor NOC18 induces HIF-1alpha synthesis under conditions of NO formation during normoxia and that hydroxylation of HIF-1alpha is not regulated by NOC18... - Regulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by an insulin-like growth factor-I receptor autocrine loop in human pancreatic cancerOliver Stoeltzing
Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 4009, USA
Am J Pathol 163:1001-11. 2003..02). Our results suggest that autocrine activation of the IGF-IR system significantly affects VEGF expression and angiogenesis in human pancreatic cancer. Thus, IGF-IR may be a valid target in the treatment of pancreatic cancer... - Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1 alphaDavid D Kline
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Proc Natl Acad Sci U S A 99:821-6. 2002..Thus partial HIF-1 alpha deficiency has a dramatic effect on carotid body neural activity and ventilatory adaptation to chronic hypoxia... - Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancerPeter Buchler
Department of Surgery, UCLA School of Medicine, Los Angeles, California 90095 6904, USA
Pancreas 26:56-64. 2003..The microenvironment of low oxygen that is present in human pancreatic cancer in vivo may actively influence tumor growth as well as neovascularization... - Disruption of oxygen homeostasis underlies congenital Chuvash polycythemiaSonny O Ang
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA
Nat Genet 32:614-21. 2002.... - Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathwayCaroline Treins
INSERM U145, , , Avenue de Valombrose, 06107 Nice Cedex 2, France
J Biol Chem 277:27975-81. 2002..HIF-1 activity and VEGF expression are also dependent on PI3K- and TOR-dependent signaling. In conclusion, we show here that insulin regulates HIF-1 action through a PI3K/TOR-dependent pathway, resulting in increased VEGF expression... - Heterozygous HIF-1alpha deficiency impairs carotid body-mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxiaYing Jie Peng
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44109, USA
J Physiol 577:705-16. 2006.... - ROS signaling in systemic and cellular responses to chronic intermittent hypoxiaNanduri R Prabhakar
Center for Systems Biology, Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
Antioxid Redox Signal 9:1397-403. 2007.... - Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturationOliver Stoeltzing
Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, Houston 77030 4009, USA
J Natl Cancer Inst 96:946-56. 2004..Overexpression of HIF-1alpha is associated with tumor angiogenesis and tumor cell proliferation and invasion. We examined the effects of inhibiting HIF-1alpha activity on angiogenesis and human gastric cancer growth in vivo... - Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor signalingKiichi Hirota
Department of Anesthesia, The Tazuke Kofukai Medical Research Institute Kitano Hospital, 2 4 20, Ohgimachi, Kita ku, Osaka 530 8480, Japan
J Biol Chem 279:41521-8. 2004..We conclude that muscarinic acetylcholine signals activate HIF-1 by both stabilization and synthesis of HIF-1alpha and by inducing the transcriptional activity of HIF-1alpha... - The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathwaySatoshi Takabuchi
Department of Anesthesia, The Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan
Biochem Biophys Res Commun 324:417-23. 2004..SNP inhibits the accumulation of HIF-1alpha, the regulatory subunit of HIF-1, and the transcriptional activation of HIF-1alpha via a mechanism that is not dependent on either NO or soluble guanylate cyclase... - Ca2+/calmodulin kinase-dependent activation of hypoxia inducible factor 1 transcriptional activity in cells subjected to intermittent hypoxiaGuoxiang Yuan
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
J Biol Chem 280:4321-8. 2005..These observations suggest that IH induces HIF-1 transcriptional activity via a novel signaling pathway involving CaM kinase... - The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity in an oxygen tension-dependent mannerSatoshi Takabuchi
Department of Anesthesia, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, 2 4 20, Ohgimachi, Kita ku, Osaka 530 8480, Japan
FEBS Lett 577:434-8. 2004.... - Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathwaysQing Xu
H Lee Moffitt Cancer Center and Research Institute, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, FL 33612, USA
Oncogene 24:5552-60. 2005..Activation of Stat3 signaling by various growth signaling is prevalent in diverse cancers. Results presented here demonstrate that Stat3 is an effective target for inhibiting tumor VEGF expression and angiogenesis... - Induction of HIF-1alpha expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTORGuoxiang Yuan
The Center for Systems Biology, Department of Medicine, University of Chicago, Illinois 60637, USA
J Cell Physiol 217:674-85. 2008..Rapamycin or cycloheximide, blocked increased HIF-1alpha levels during re-oxygenation indicating that mTOR-dependent protein synthesis is required for the persistent elevation of HIF-1alpha levels during re-oxygenation... - HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomasMichael J Gray
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcomb Boulevard, Houston, TX 77030, USA
Oncogene 24:3110-20. 2005..These data suggest that the binding of both STAT3 and HIF-1alpha to the VEGF promoter is required for maximum transcription of VEGF mRNA following hypoxia...
Research Grants
- EXPRESSION OF HUMAN ERYTHROPOIETIN GENEGregg Semenza; Fiscal Year: 2002..abstract_text> ..
- HYPOXIA INDUCIBLE FACTOR I AND OXYGEN HOMEOSTASISGregg Semenza; Fiscal Year: 2004..The knowledge gained from the proposed experiments will be relevant to the treatment of many clinical conditions in which hypoxia or ischemia plays an important pathophysiologic role. ..
- HIF-1-Regulated Endothelial Progenitor Cell Recruitment in Burn Wound HealingGregg Semenza; Fiscal Year: 2007....
- HIF-1-Regulated Endothelial Progenitor Cell Recruitment in Burn Wound HealingGregg Semenza; Fiscal Year: 2007..abstract_text> ..
- Hypoxia-Inducible Factor 1 and Oxygen HomeostasisGregg Semenza; Fiscal Year: 2009....
- HYPOXIA INDUCIBLE FACTOR 1 AND OXYGEN HOMEOSTASISGregg Semenza; Fiscal Year: 1999....
- EXPRESSION OF HUMAN ERYTHROPOIETIN GENEGregg Semenza; Fiscal Year: 1993..EPO gene DNA from affected family members will be amplified by the polymerase chain reaction and analyzed by nucleotide sequence determination to identify potential disease-causing mutations...