Genomes and Genes
Affiliation: Genzyme Corporation
- In vitro cystogenesis: the search for drugs antagonizing cyst developmentOxana Ibraghimov-Beskrovnaya
Genzyme Corporation, 5, Mountain Road, Framingham, MA 01701 9322, Etats Unis
Nephrol Ther 2:S109-14. 2006..We have used in vitro cystogenesis assay for a high throughput screen of small molecule drugs and identified drugs specifically inhibiting cystogenesis but not tubulogenesis in vitro...
- mTOR signaling in polycystic kidney diseaseOxana Ibraghimov-Beskrovnaya
Cell Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA, USA
Trends Mol Med 17:625-33. 2011..We discuss the mTOR pathway in depth, highlighting recent progress in understanding its role in PKD and the current results of clinical trials...
- Polycystic kidney diseases: from molecular discoveries to targeted therapeutic strategiesO Ibraghimov-Beskrovnaya
Cell Biology, Genzyme Corporation, 5 Mountain Road, Framingham, MA 01701 9322, USA
Cell Mol Life Sci 65:605-19. 2008..We discuss available models and challenges for therapeutic discovery as well as summarize the results from preclinical experimental treatments targeting key disease-specific pathways...
- Targeting dysregulated cell cycle and apoptosis for polycystic kidney disease therapyOxana Ibraghimov-Beskrovnaya
Genzyme Corporation, Framingham, Massachusetts 01701, USA
Cell Cycle 6:776-9. 2007..Thus, therapies directly targeting coordinate regulation of proliferation and apoptosis are emerging as effective approaches to treat multiple renal diseases...
- Pkd1 and Nek8 mutations affect cell-cell adhesion and cilia in cysts formed in kidney organ culturesThomas A Natoli
Department of Cell Biology, Genzyme Corporation, 5 Mountain Rd, Framingham, MA 01701 9322, USA
Am J Physiol Renal Physiol 294:F73-83. 2008..Therefore, embryonic kidney organ culture represents a relevant model for studying molecular cystogenesis and a rapid tool for the screening for therapies that block cystic growth...
- Functional polycystin-1 expression is developmentally regulated during epithelial morphogenesis in vitro: downregulation and loss of membrane localization during cystogenesisNikolay O Bukanov
Genzyme Corporation, 5 Mountain Road, Framingham, MA 01701 9322, USA
Hum Mol Genet 11:923-36. 2002..We suggest that the loss of polycystin-1 from its basolateral location in tubular epithelium may alter critical pathways controlling normal tubulogenesis leading to cystic transformation...
- Development of polycystic kidney disease in juvenile cystic kidney mice: insights into pathogenesis, ciliary abnormalities, and common features with human diseaseLaurie A Smith
Genzyme Corporation, 5 Mountain Road, Framingham, MA 01701 9322, USA
J Am Soc Nephrol 17:2821-31. 2006..Collectively, these data demonstrate that the jck mice should be useful for testing potential therapies and for studying the molecular mechanisms that link ciliary structure/function and cystogenesis...
- Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse modelsThomas A Natoli
Department of Cell Biology, Genzyme Corporation, Framingham, Massachusetts, USA
Nat Med 16:788-92. 2010..Taken together, our data suggest that inhibition of GlcCer synthesis represents a new and effective treatment option for PKD...
- Loss of GM3 synthase gene, but not sphingosine kinase 1, is protective against murine nephronophthisis-related polycystic kidney diseaseThomas A Natoli
Department of Cell Biology, Genzyme Corporation, Framingham, MA 01701, USA
Hum Mol Genet 21:3397-407. 2012..Together, these data suggest that genes involved in the SL metabolism may be modifiers of cystogenesis, and suggest GM3 synthase as a new anti-cystic therapeutic target...
- Serum and urinary biomarker signatures for rapid preclinical in vivo assessment of CDK inhibition as a therapeutic approach for PKDSarah Moreno
Cell Biology, Genzyme Corporation, Framingham, Massachusetts 01701 9322, USA
Cell Cycle 7:1856-64. 2008..This biomarker signature provides a necessary tool for further assessment of CDK inhibitors as therapeutic agents for PKD...
- Canine PKD1 is a single-copy gene: genomic organization and comparative analysisWilliam R Dackowski
Genzyme Corporation, 5 Mountain Road, Framingham, Massachusetts, 01701 9322, USA
Genomics 80:105-12. 2002..These data enable detailed analysis of the role of polycystin-1 in cystogenesis and tubulogenesis using the canine MDCK cell line...
- Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitineNikolay O Bukanov
Cell Biology, Genzyme Corporation, 5 Mountain Road, Framingham, Massachusetts 01701-9322, USA
Nature 444:949-52. 2006..Our results indicate that inhibition of CDK is a new and effective approach to the treatment of PKD...
- Impaired formation of desmosomal junctions in ADPKD epitheliaRyan J Russo
Genzyme Corporation, 5 Mountain Road, Framingham, MA 01701-9322, USA
Histochem Cell Biol 124:487-97. 2005..We propose that abnormal expression of PC-1 causes disregulation of cellular adhesion complexes leading to increased proliferation, loss of polarity and, ultimately, cystogenesis...
- New insights into ADPKD molecular pathways using combination of SAGE and microarray technologiesHerve Husson
Functional Genomics, Genzyme Corporation, Framingham, MA 01701 9322, USA
Genomics 84:497-510. 2004..01. This study may provide valuable insights into the pathophysiology of ADPKD and suggest potential therapeutic targets...
- Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminusVeronique Chauvet
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
J Clin Invest 114:1433-43. 2004..Polycystin-2, the product of the second gene mutated in ADPKD, modulates the signaling properties of the polycystin-1 CTT. These data reveal a novel pathway by which polycystin-1 transmits messages directly to the nucleus...
- Molecular pathogenesis of ADPKD and development of targeted therapeutic optionsOxana Ibraghimov-Beskrovnaya
Nephrol Dial Transplant 22:3367-70. 2007
- Functional analysis of PKD1 transgenic lines reveals a direct role for polycystin-1 in mediating cell-cell adhesionAndrew J Streets
Sheffield Kidney Institute, Division of Clinical Sciences North, University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK
J Am Soc Nephrol 14:1804-15. 2003..Disruption of cell-cell adhesion during tubular morphogenesis may be an early initiating event for cyst formation in ADPKD...
- Cation channel regulation by COOH-terminal cytoplasmic tail of polycystin-1: mutational and functional analysisDavid H Vandorpe
Molecular Medicine, Beth Israel Deaconess Medical Center, Boston 02215, USA
Physiol Genomics 8:87-98. 2002..The divalent cation permeability and pharmacological profile of the current has been extended. Inducible expression of the PKD1 fusion in EcR-293 cells was also associated with activation of cation channels and increased Ca2+ entry...