Research Topics
Genomes and Genes
| Michael OhhSummaryAffiliation: University of Toronto Country: Canada Publications
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Detail Information
Publications
Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinomaMindy A Maynard
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
FASEB J 19:1396-406. 2005..These results demonstrate an important dominant-negative regulation of HIF-1-mediated gene transcription by HIF-3alpha4 in vivo and underscore its potential significance in renal epithelial oncogenesis...
Characterization of a von Hippel Lindau pathway involved in extracellular matrix remodeling, cell invasion, and angiogenesisGhada Kurban
McGill Cancer Center and Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
Cancer Res 66:1313-9. 2006..We conclude that loss of ECM integrity could promote and maintain tumor angiogenesis by providing a route for blood vessels to infiltrate tumors...
pVHL's kryptonite: E2-EPF UCPMichael Ohh
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
Cancer Cell 10:95-7. 2006....
Loss of VHL confers hypoxia-inducible factor (HIF)-dependent resistance to vesicular stomatitis virus: role of HIF in antiviral responseIrene I L Hwang
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
J Virol 80:10712-23. 2006..These results reveal a previously unrecognized role of HIF in the antiviral response by promoting the expression of the IFN-beta gene and other genes with antiviral activity upon viral infection...
Role of the NEDD8 modification of Cul2 in the sequential activation of ECV complexRoxana I Sufan
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
Neoplasia 8:956-63. 2006..These events establish a central role for the neddylation of Cul2 in a previously unrecognized, temporally coordinated activation of ECV with the recruitment of its substrate HIFalpha...
Molecular targets from VHL studies into the oxygen-sensing pathwayM A Maynard
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King s College Circle, Toronto, Ontario, M5S 1A8, Canada
Curr Cancer Drug Targets 5:345-56. 2005....
Ubiquitin pathway in VHL cancer syndromeMichael Ohh
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada
Neoplasia 8:623-9. 2006..This review will examine recent progress in our understanding of the molecular mechanisms governing the function of ECV and the significance of consequential regulation of HIF in oncogenesis...
pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor developmentNatalie H Stickle
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Mol Cell Biol 24:3251-61. 2004..These results suggest that NEDD8 modification of pVHL plays an important role in fibronectin matrix assembly and that in the absence of such regulation, an intact HIF pathway is insufficient to prevent VHL-associated tumorigenesis...
Oxygen-independent degradation of HIF-alpha via bioengineered VHL tumour suppressor complexRoxana I Sufan
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
EMBO Mol Med 1:66-78. 2009..These findings introduce the concept and feasibility of 'bio-tailored' enzymes in the treatment of HIF-overexpressing tumours...
Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinomaMichelle L Gervais
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
Lab Invest 87:1252-64. 2007..These findings provide the first evidence of aberrant nuclear localization of E-cadherin in CC-RCC harboring VHL mutations, and suggest potential prognostic value of VHL and E-cadherin in CC-RCC...
Hypoxia promotes ligand-independent EGF receptor signaling via hypoxia-inducible factor-mediated upregulation of caveolin-1Yi Wang
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 1A8
Proc Natl Acad Sci U S A 109:4892-7. 2012....
Molecular cloning and characterization of the von Hippel-Lindau-like proteinHeng Qi
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
Mol Cancer Res 2:43-52. 2004..These results taken together indicate that VLP functions as a dominant-negative VHL to serve as a protector of HIFalpha...
Oncolytic targeting of renal cell carcinoma via encephalomyocarditis virusFrederik C Roos
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
EMBO Mol Med 2:275-88. 2010..These findings provide compelling pre-clinical evidence for the usage of EMCV in the treatment of CCRCC and potentially other tumours with elevated HIF/NF-kappaB-survival signature...
VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snailAndrew J Evans
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
Mol Cell Biol 27:157-69. 2007..These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin...
Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation functionIan R Watson
Cancer Research Program and Division of Haematology Oncology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
J Biol Chem 281:34096-103. 2006....
Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progressionMindy A Maynard
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Cell Cycle 6:2810-6. 2007....
NEDD8 acts as a 'molecular switch' defining the functional selectivity of VHLRyan C Russell
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
EMBO Rep 9:486-91. 2008..These findings provide the first mechanistic step in defining the functional selectivity of VHL and explain a previously unrecognized function of NEDD8...
Von Hippel-Lindau tumor suppressor protein and hypoxia-inducible factor in kidney cancerMindy A Maynard
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ont, Canada
Am J Nephrol 24:1-13. 2004..Our current molecular understanding of the roles of HIF and pVHL in the development of VHL-associated clear-cell renal cell carcinoma (CC-RCC) is the focus of this review...
Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemiaRyan C Russell
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Nat Med 17:845-53. 2011..These results show that VHL is a SOCS1-cooperative negative regulator of JAK2 and provide biochemical and preclinical support for JAK2-targeted therapy in individuals with Chuvash polycythemia...
The updated biology of hypoxia-inducible factorSamantha N Greer
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada
EMBO J 31:2448-60. 2012....
NEDD8 pathways in cancer, Sine Quibus NonIan R Watson
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Cancer Cell 19:168-76. 2011....
Suppression of hypoxia-inducible factor 2alpha restores p53 activity via Hdm2 and reverses chemoresistance of renal carcinoma cellsAndrew M Roberts
Department of Laboratory Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Cancer Res 69:9056-64. 2009..These findings unveil a mechanistic link between HIF2alpha and p53 and provide a rationale for combining Hdm2 antagonists with chemotherapy for the treatment of CCRCC...
Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinomaFrederik C Roos
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Am J Pathol 178:853-60. 2011..These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC...
Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complexMindy A Maynard
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
J Biol Chem 278:11032-40. 2003..These results demonstrate additional targets of the pVHL complex and suggest a growing complexity in the regulation of hypoxia-inducible genes by the HIF family of transcription factors...
Expression of p53 in renal carcinoma cells is independent of pVHLNatalie H Stickle
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ont, Canada M5S 1A8
Mutat Res 578:23-32. 2005..These results suggest that the expression of p53 in RCC cells is independent of pVHL...
The role of von Hippel-Lindau tumor suppressor protein and hypoxia in renal clear cell carcinomaRoxana I Sufan
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8
Am J Physiol Renal Physiol 287:F1-6. 2004..Recent insights into the molecular mechanisms regulating the function of pVHL, and thereby HIF, in the context of kidney cancer are the focus of this review...
Oxygen-mediated endocytosis in cancerYi Wang
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
J Cell Mol Med 14:496-503. 2010..These recent discoveries underscore the emergence of endocytosis as an important hypoxia-mediated regulatory process in cancer...
The role of VHL in the regulation of E-cadherin: a new connection in an old pathwayRyan C Russell
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Cell Cycle 6:56-9. 2007..This review highlights recent discoveries uncovering the transcriptional regulation of E-cadherin, a homophilic cell adhesion molecule with anti-invasive properties in numerous epithelial-derived cancers, via the VHL-HIF pathway...
Functional importance of Dicer protein in the adaptive cellular response to hypoxiaJ J David Ho
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5B 1W8, Canada
J Biol Chem 287:29003-20. 2012....
The von Hippel-Lindau tumor suppressor protein sensitizes renal cell carcinoma cells to tumor necrosis factor-induced cytotoxicity by suppressing the nuclear factor-kappaB-dependent antiapoptotic pathwayHeng Qi
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
Cancer Res 63:7076-80. 2003....
SATB2 augments ΔNp63α in head and neck squamous cell carcinomaJacky Chung
Department of Molecular Genetics, University of Toronto, Cell Biology Program, Hospital for Sick Children Research Institute, Department of Paediatrics, 555 University Avenue, Toronto, Ontario, M5G 1L7, Canada
EMBO Rep 11:777-83. 2010..These findings unveil SATB2 as a pivotal modulator of ΔNp63α that governs HNSCC cell survival...
Regulation of endocytosis via the oxygen-sensing pathwayYi Wang
Department of Laboratory Medicine and Pathobiology, St Michael s Hospital, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
Nat Med 15:319-24. 2009....
Transcriptional regulation of genes via hypoxia-inducible factorOlga Roche
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Methods Mol Biol 809:189-99. 2012..Here, we describe classical experimental approaches to demonstrate and validate HIF-responsive transcriptional regulation of genes...
Hypoxia-inducible expression of a natural cis-antisense transcript inhibits endothelial nitric-oxide synthaseJason E Fish
Department of Medical Biophysics, St Michael s Hospital, University of Toronto, Toronto, Ontario M5S 1A8, Canada
J Biol Chem 282:15652-66. 2007....
Beyond the hypoxia-inducible factor-centric tumour suppressor model of von Hippel-LindauAndrew M Roberts
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
Curr Opin Oncol 20:83-9. 2008..To provide an overview of the recent advances in the understanding of the molecular mechanisms governing the tumour suppressor functions of the von Hippel-Lindau protein...
Homotypic association between tumour-associated VHL proteins leads to the restoration of HIF pathwayJ Chung
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
Oncogene 25:3079-83. 2006....
Chemotherapy induces NEDP1-mediated destabilization of MDM2I R Watson
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Oncogene 29:297-304. 2010..These findings unveil the regulation of MDM2 stability through NEDP1 as a common molecular determinant governing chemotherapy-induced p53-dependent cell death...
The role of hypoxia-inducible factors in cancerM A Maynard
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, M5S1A8, Toronto, Ontario, Canada
Cell Mol Life Sci 64:2170-80. 2007....
Diverse effects of mutations in exon II of the von Hippel-Lindau (VHL) tumor suppressor gene on the interaction of pVHL with the cytosolic chaperonin and pVHL-dependent ubiquitin ligase activityWilliam J Hansen
Surgical Research Laboratory, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA
Mol Cell Biol 22:1947-60. 2002....
von Hippel-Lindau tumor suppressor protein regulates the assembly of intercellular junctions in renal cancer cells through hypoxia-inducible factor-independent mechanismsMaria J Calzada
, Hospital de la Princesa, Departamento de Medicina, , , 28006 Madrid, Spain
Cancer Res 66:1553-60. 2006..In summary, we show that VHL inactivation in RCC cells disrupts intercellular junctions and cell shape through HIF-independent events, supporting the concept that VHL has additional functions beside its role in the regulation of HIF...
VHL and kidney cancerMichael Ohh
Dana-Farber Cancer Institute, Boston, MA, USA
Methods Mol Biol 222:167-83. 2003
An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cellsMichael Ohh
Department of Adult Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
EMBO Rep 3:177-82. 2002..Thus, neddylation regulates the activity of two specific subclasses of mammalian ubiquitin ligases...
Somatic pairing of chromosome 19 in renal oncocytoma is associated with deregulated EGLN2-mediated [corrected] oxygen-sensing responseJulie M Koeman
Laboratory of Germline Modification and Cytogenetics, Van Andel Research Institute, Grand Rapids, Michigan, United States of America
PLoS Genet 4:e1000176. 2008..The identification of EGLN2 as a significantly deregulated gene that maps within the paired chromosome region directly implicates defects in the oxygen-sensing network to the biology of renal oncocytoma...
Tumor suppression by the von Hippel-Lindau protein requires phosphorylation of the acidic domainMartijn P Lolkema
Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
J Biol Chem 280:22205-11. 2005..We propose that phosphorylation of the acidic domain plays a role in the regulation of proper fibronectin matrix deposition and that this may be relevant for the development of VHL-associated malignancies...
