down regulation


Summary: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

Top Publications

  1. pmc MicroRNA targeting specificity in mammals: determinants beyond seed pairing
    Andrew Grimson
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 27:91-105. 2007
  2. ncbi Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs
    Lee P Lim
    Rosetta Inpharmatics, Merck and Co, 401 Terry Avenue N, Seattle, Washington 98109, USA
    Nature 433:769-73. 2005
  3. pmc Significance analysis of microarrays applied to the ionizing radiation response
    V G Tusher
    Departments of Medicine and Biochemistry, Stanford University, 269 Campus Drive, Center for Clinical Sciences Research 1115, Stanford, CA 94305-5151, USA
    Proc Natl Acad Sci U S A 98:5116-21. 2001
  4. ncbi PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
    Vamsi K Mootha
    Whitehead Institute MIT Center for Genome Research, Cambridge, Massachusetts, USA
    Nat Genet 34:267-73. 2003
  5. doi Widespread changes in protein synthesis induced by microRNAs
    Matthias Selbach
    Max Delbruck Center for Molecular Medicine, Robert Rossle Str 10, D 13125 Berlin, Germany
    Nature 455:58-63. 2008
  6. ncbi Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells
    H Niwa
    Centre for Genome Research, The University of Edinburgh, King s Buildings, Edinburgh, UK
    Nat Genet 24:372-6. 2000
  7. ncbi A system for stable expression of short interfering RNAs in mammalian cells
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis, Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands
    Science 296:550-3. 2002
  8. ncbi Mdm2 promotes the rapid degradation of p53
    Y Haupt
    Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem, Israel
    Nature 387:296-9. 1997
  9. ncbi MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer
    I A Asangani
    Department of Experimental Surgery and Molecular Oncology of Solid Tumors, Medical Faculty Mannheim, University of Heidelberg, Germany
    Oncogene 27:2128-36. 2008
  10. ncbi Silencing of microRNAs in vivo with 'antagomirs'
    Jan Krutzfeldt
    Laboratory of Metabolic Diseases, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 438:685-9. 2005

Detail Information

Publications384 found, 100 shown here

  1. pmc MicroRNA targeting specificity in mammals: determinants beyond seed pairing
    Andrew Grimson
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 27:91-105. 2007
    ..Because it predicts site efficacy without recourse to evolutionary conservation, the model also identifies effective nonconserved sites and siRNA off-targets...
  2. ncbi Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs
    Lee P Lim
    Rosetta Inpharmatics, Merck and Co, 401 Terry Avenue N, Seattle, Washington 98109, USA
    Nature 433:769-73. 2005
    ..Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans...
  3. pmc Significance analysis of microarrays applied to the ionizing radiation response
    V G Tusher
    Departments of Medicine and Biochemistry, Stanford University, 269 Campus Drive, Center for Clinical Sciences Research 1115, Stanford, CA 94305-5151, USA
    Proc Natl Acad Sci U S A 98:5116-21. 2001
    ..Surprisingly, four nucleotide excision repair genes were induced, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation...
  4. ncbi PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
    Vamsi K Mootha
    Whitehead Institute MIT Center for Genome Research, Cambridge, Massachusetts, USA
    Nat Genet 34:267-73. 2003
    ..Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments...
  5. doi Widespread changes in protein synthesis induced by microRNAs
    Matthias Selbach
    Max Delbruck Center for Molecular Medicine, Robert Rossle Str 10, D 13125 Berlin, Germany
    Nature 455:58-63. 2008
    ..Finally, our data suggest that a miRNA can, by direct or indirect effects, tune protein synthesis from thousands of genes...
  6. ncbi Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells
    H Niwa
    Centre for Genome Research, The University of Edinburgh, King s Buildings, Edinburgh, UK
    Nat Genet 24:372-6. 2000
  7. ncbi A system for stable expression of short interfering RNAs in mammalian cells
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis, Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands
    Science 296:550-3. 2002
    ..Therefore, the pSUPER vector constitutes a new and powerful system to analyze gene function in a variety of mammalian cell types...
  8. ncbi Mdm2 promotes the rapid degradation of p53
    Y Haupt
    Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem, Israel
    Nature 387:296-9. 1997
    ..During recovery from DNA damage, maximal Mdm2 induction coincides with rapid p53 loss. We propose that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal...
  9. ncbi MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer
    I A Asangani
    Department of Experimental Surgery and Molecular Oncology of Solid Tumors, Medical Faculty Mannheim, University of Heidelberg, Germany
    Oncogene 27:2128-36. 2008
    ..This is the first study to show that Pdcd4 is negatively regulated by miR-21. Furthermore, it is the first report to demonstrate that miR-21 induces invasion/intravasation/metastasis...
  10. ncbi Silencing of microRNAs in vivo with 'antagomirs'
    Jan Krutzfeldt
    Laboratory of Metabolic Diseases, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 438:685-9. 2005
    ..Our findings show that antagomirs are powerful tools to silence specific miRNAs in vivo and may represent a therapeutic strategy for silencing miRNAs in disease...
  11. ncbi Serine phosphorylation-independent downregulation of cell-surface CD4 by nef
    J V Garcia
    Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104
    Nature 350:508-11. 1991
    ..Also, nef can downregulate a CD4 triple mutant (Ser----Ala) that is neither phosphorylated nor down-regulated by phorbol esters, indicating that nef is acting by a different mechanism...
  12. ncbi MicroRNA-directed cleavage of HOXB8 mRNA
    Soraya Yekta
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 304:594-6. 2004
  13. pmc MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma
    H C Chen
    Genomic Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taiwan, Republic of China
    Br J Cancer 100:1002-11. 2009
    ..These results indicate that these downregulated miRNAs coordinately regulate several oncogenic pathways in NPC...
  14. ncbi The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells
    E Batlle
    Unitat de Biologia Cel lular i Molecular, Institut Municipal d Investigacio Medica, Universitat Pompeu Fabra, Dr Aiguader 80, 08003 Barcelona, Spain
    Nat Cell Biol 2:84-9. 2000
    ..Inhibition of Snail function in epithelial cancer cell lines lacking E-cadherin protein restores the expression of the E-cadherin gene...
  15. pmc Links between signal transduction, transcription and adhesion in epithelial bud development
    Colin Jamora
    Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10021, USA
    Nature 422:317-22. 2003
  16. pmc The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein
    Nanette Van Damme
    The San Diego Department of Veterans Affairs Healthcare System, San Diego, CA 92161, USA
    Cell Host Microbe 3:245-52. 2008
  17. pmc miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements
    Ashish Lal
    Immune Disease Institute, Children s Hospital Boston, Department of Pediatrics, Harvard Medical School, MA 02115, USA
    Mol Cell 35:610-25. 2009
    ..The E2F2 3'UTR lacks a predicted miR-24 recognition element. In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4, and FEN1 by recognizing seedless but highly complementary sequences...
  18. ncbi Myostatin inhibits myoblast differentiation by down-regulating MyoD expression
    Brett Langley
    Animal Genomics, AgResearch, Private Bag 3123, East Street, Hamilton, New Zealand
    J Biol Chem 277:49831-40. 2002
  19. ncbi A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions
    M A Perez-Moreno
    Instituto de Investigaciones Biomedicas Alberto Sols CSIC UAM, Arturo Duperier, 4, Madrid 28029, Spain
    J Biol Chem 276:27424-31. 2001
    ..These results implicate E12/E47 as a repressor of E-cadherin expression during both development and tumor progression and indicate its involvement in the acquisition and/or maintenance of the mesenchymal phenotype...
  20. pmc MicroRNAs direct rapid deadenylation of mRNA
    Ligang Wu
    Skirball Institute of Biomolecular Medicine and Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 103:4034-9. 2006
    ..These findings suggest that miRNAs use two distinct posttranscriptional mechanisms to down-regulate gene expression...
  21. ncbi Perspective: machines for RNAi
    Yukihide Tomari
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Genes Dev 19:517-29. 2005
    ..Here, we review our current understanding of how small RNAs are produced, how they are loaded into protein complexes, and how they repress gene expression...
  22. ncbi Widespread deregulation of microRNA expression in human prostate cancer
    M Ozen
    Department of Pathology, Baylor College of Medicine, Houston, TX, USA
    Oncogene 27:1788-93. 2008
    ..Our findings indicate that changes in miRNA expression may have an important role in the biology of human prostate cancer...
  23. ncbi Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock
    Esmerina Tili
    Ohio State University, Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Columbus, OH 43210, USA
    J Immunol 179:5082-9. 2007
    ..Altogether, our data suggest that the LPS/TNF-alpha-dependent regulation of miR-155 and miR-125b may be implicated in the response to endotoxin shock, thus offering new targets for drug design...
  24. pmc Modulation of different human immunodeficiency virus type 1 Nef functions during progression to AIDS
    S Carl
    Institute for Clinical and Molecular Virology, Friedrich-Alexander University, D-91054 Erlangen, Germany
    J Virol 75:3657-65. 2001
    ..These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals...
  25. pmc Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection
    Steffen Wildum
    Department of Virology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany
    J Virol 80:8047-59. 2006
    ..Accordingly, one reason that HIV-1 inhibits CD4 surface expression and superinfection is to prevent premature cell death in order to expand the period of effective virus production...
  26. ncbi Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis
    Satoru Funamoto
    Section of Cell and Developmental Biology, Division of Biology, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 109:611-23. 2002
    ..These findings provide evidence that differential subcellular localization and activation of PI3K and PTEN is required for proper chemotaxis...
  27. ncbi T cell receptor signaling precedes immunological synapse formation
    Kyeong Hee Lee
    Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, Box 8118, Saint Louis, MO 63110, USA
    Science 295:1539-42. 2002
    ..These data suggest that many hours of TCR signaling are not required for T cell activation. These observations challenge current ideas about the role of immunological synapses in T cell activation...
  28. ncbi Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein
    O Schwartz
    Laboratoire Rétrovirus et Transfert Génétique, Unité de Recherche Associée CNRS 1157, Paris, France
    Nat Med 2:338-42. 1996
    ..The stimulation of MHC-I endocytosis by Nef represents a previously undocumented viral mechanism for evading the immune response...
  29. pmc Selective blockade of microRNA processing by Lin28
    Srinivas R Viswanathan
    Stem Cell Program, Children s Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA
    Science 320:97-100. 2008
    ..Our results identify Lin28 as a negative regulator of miRNA biogenesis and suggest that Lin28 may play a central role in blocking miRNA-mediated differentiation in stem cells and in certain cancers...
  30. ncbi Francisella tularensis LVS initially activates but subsequently down-regulates intracellular signaling and cytokine secretion in mouse monocytic and human peripheral blood mononuclear cells
    Max Telepnev
    Department of Clinical Microbiology, Clinical Bacteriology, Umea University, Umea, SE 901 87, Sweden
    Microb Pathog 38:239-47. 2005
    ..This down-regulation does not occur when cells are infected with the mutant deltaiglC...
  31. doi Decreased expression of microRNA-143 and -145 in human gastric cancers
    Takeshi Takagi
    Department of Medical Oncology, Gifu International Institute of Biotechnology, Kakamigahara, Japan
    Oncology 77:12-21. 2009
    ..Downregulation of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. We investigated the role of the miRNAs miR-143 and miR-145 in gastric cancers...
  32. pmc The role of microRNA genes in papillary thyroid carcinoma
    Huiling He
    Human Cancer Genetics Program, Department of Pathology, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 102:19075-80. 2005
    ..We conclude that up-regulation of several miRs and regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their regulation...
  33. pmc Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state
    K D McCullough
    Cell Stress and Aging Section, Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 6825, USA
    Mol Cell Biol 21:1249-59. 2001
    ..We conclude that Gadd153 sensitizes cells to ER stress through mechanisms that involve down-regulation of Bcl2 and enhanced oxidant injury...
  34. ncbi Death and anti-death: tumour resistance to apoptosis
    Frederik H Igney
    Tumor Immunology Program, German Cancer Research Center DKFZ, Heidelberg
    Nat Rev Cancer 2:277-88. 2002
    ..So, what are the molecular mechanisms of tumour resistance to apoptosis and how can we use this knowledge to resensitize tumour cells to cancer therapy?..
  35. ncbi Genome-wide analysis of estrogen receptor binding sites
    Jason S Carroll
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney St, Boston, Massachusetts 02115, USA
    Nat Genet 38:1289-97. 2006
    ..Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer...
  36. ncbi DRAM, a p53-induced modulator of autophagy, is critical for apoptosis
    Diane Crighton
    Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
    Cell 126:121-34. 2006
    ..Collectively therefore, these studies not only report a stress-induced regulator of autophagy but also highlight the relationship of DRAM and autophagy to p53 function and damage-induced programmed cell death...
  37. ncbi The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis
    J Oh
    Department of Molecular Oncology, Kyoto University Graduate School of Medicine, 606 8501, Kyoto, Japan
    Cell 107:789-800. 2001
    ..These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis...
  38. ncbi Negative regulation of toll-like receptor-mediated immune responses
    Foo Y Liew
    Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow G11 6NT, UK
    Nat Rev Immunol 5:446-58. 2005
    ..Here, we discuss the various negative regulatory mechanisms that have evolved to attenuate TLR signalling to maintain this immunological balance...
  39. ncbi Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity
    M Karin
    Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction University of California, San Diego, La Jolla, California 92093 0636, USA
    Annu Rev Immunol 18:621-63. 2000
  40. pmc Muscle-specific microRNA miR-206 promotes muscle differentiation
    Hak Kyun Kim
    Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
    J Cell Biol 174:677-87. 2006
    ..In addition, inhibitors of myogenic transcription factors, Id1-3 and MyoR, are decreased upon miR-206 introduction, suggesting the presence of additional mechanisms by which microRNAs enforce the differentiation program...
  41. ncbi Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain
    C Aiken
    Infectious Disease Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037 1099
    Cell 76:853-64. 1994
    ..Within this region, a dileucine motif, reminiscent of an endocytosis and lysosomal targeting signal found in the CD3 gamma and delta chains, is crucial for CD4 response to Nef...
  42. ncbi Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide
    M T Abreu
    Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, Cedars Sinai Medical Center, 8631 West 3rd Street, Los Angeles, CA 90048, USA
    J Immunol 167:1609-16. 2001
    ..We conclude that IEC limit dysregulated LPS signaling by down-regulating expression of MD-2 and TLR4. The remainder of the intracellular LPS signaling pathway is functionally intact...
  43. ncbi The Fas death factor
    S Nagata
    Osaka Bioscience Institute, Japan
    Science 267:1449-56. 1995
    ..Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction...
  44. ncbi The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells
    G B Cohen
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Immunity 10:661-71. 1999
    ..These results suggest that subpopulations of CTL and NK cells may be uniquely suited for combating HIV...
  45. pmc MDM2 promotes ubiquitination and degradation of MDMX
    Yu Pan
    Molecular Oncology Program, H Lee Moffitt Comprehensive Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
    Mol Cell Biol 23:5113-21. 2003
    ..The ARF tumor suppressor differentially regulates the ability of MDM2 to promote p53 and MDMX ubiquitination and activates p53 by targeting both members of the MDM2 family...
  46. pmc MiR-15a and miR-16-1 cluster functions in human leukemia
    George A Calin
    Human Cancer Genetics Program and Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 105:5166-71. 2008
    ..By examining the Gene Ontology (GO) database, a significant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly affect apoptosis and cell cycle was found...
  47. ncbi beta-catenin interacts with and inhibits NF-kappa B in human colon and breast cancer
    Jiong Deng
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Cell 2:323-34. 2002
    ..Thus, beta-catenin may play an important role in oncogenesis through the crossregulation of NF-kappa B...
  48. ncbi The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion
    J Comijn
    Molecular Cell Biology Unit, Department of Molecular Biology, VIB Ghent University, B 9000, Ghent, Belgium
    Mol Cell 7:1267-78. 2001
    ..SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors...
  49. ncbi Repression of protein synthesis by miRNAs: how many mechanisms?
    Ramesh S Pillai
    European Molecular Biology Laboratory, Grenoble Outstation, B P 181, 38042 Grenoble Cedex 9, France
    Trends Cell Biol 17:118-26. 2007
    ..Recent data support different microRNA mechanisms and a role for cytoplasmic processing bodies in the degradation and storage of mRNAs targeted by microRNA regulators...
  50. ncbi The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer
    Jose Manuel Gonzalez-Sancho
    Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Arturo Duperier 4, E 28029 Madrid, Spain
    Oncogene 24:1098-103. 2005
    ..Our data indicate that the Wnt/beta-catenin pathway is downregulated by the induction of DKK-1 expression, a mechanism that is lost in colon cancer...
  51. ncbi The Wnt antagonist sFRP1 in colorectal tumorigenesis
    Germaine M Caldwell
    Division of Medical Sciences, School of Medicine, The University of Birmingham, Birmingham, United Kingdom
    Cancer Res 64:883-8. 2004
    ..Therefore, we propose that the reduced activity or absence of sFRP1 allows the transduction of noncanonical Wnt signals, which contribute to tumor progression...
  52. pmc Widespread microRNA repression by Myc contributes to tumorigenesis
    Tsung Cheng Chang
    McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Genet 40:43-50. 2008
    ..We further show that enforced expression of repressed miRNAs diminishes the tumorigenic potential of lymphoma cells. These results demonstrate that extensive reprogramming of the miRNA transcriptome by Myc contributes to tumorigenesis...
  53. pmc The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3'UTR
    Monica C Vella
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Genes Dev 18:132-7. 2004
  54. pmc Analysis of microarray data using Z score transformation
    Chris Cheadle
    DNA Array Unit, Research Resources Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21221, USA
    J Mol Diagn 5:73-81. 2003
    ..The results provided by these methods can be as rigorous and are no more arbitrary than other test methods, and, in addition, they have the advantage that they can be easily adapted to standard spreadsheet programs...
  55. ncbi N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation
    Yanchun Deng
    Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi an, China
    Int J Cancer 106:342-7. 2003
    ..Our findings provide the first evidence to suggest that hNDRG2 may play a role in glioblastoma carcinogenesis...
  56. ncbi Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas
    Keith Hoek
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, 15 York Street, New Haven, CT 06520 8059, USA
    Cancer Res 64:5270-82. 2004
    ..These results provide a comprehensive view of changes in advanced melanoma relative to normal melanocytes and reveal new targets that can be used in assessing prognosis, staging, and therapy of melanoma patients...
  57. doi Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells
    Shu Takakura
    Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1 12 4 Sakamoto, Nagasaki 852 8523, Japan
    Cancer Sci 99:1147-54. 2008
    ..In conclusion, these findings suggest that the miR-17-92 cluster plays an important role in certain types of ATCs and could be a novel target for ATC treatment...
  58. ncbi Down-regulation of thymidylate synthase expression and its steady-state mRNA by oxaliplatin in colon cancer cells
    Kun Huei Yeh
    Department of Internal Medicine, Far Eastern Memorial Hospital, Taiwan
    Anticancer Drugs 15:371-6. 2004
    ..Our data also suggest that TS down-regulation happens at the transcriptional level. TS modulation and down-regulation had, thus, shed light on the useful potential strategy to achieve objective responses in 5-FU-resistant CRC patients...
  59. ncbi A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2
    Lynn M Knowles
    Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 279:30540-5. 2004
    ..Altogether, the findings of the study reveal unappreciated links between fatty acid synthase and ubiquitin-dependent proteolysis of cell-cycle regulatory proteins...
  60. ncbi Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression
    Sandra Guaita
    Unitat de Biologia Cellular i Molecular, Institut Municipal d Investigacio Medica, Universitat Pompeu Fabra, E 08003 Barcelona, Spain
    J Biol Chem 277:39209-16. 2002
    ..ZEB1 could also repress E-cadherin and MUC1 promoters but less strongly than Snail. However, since ZEB1 expression persisted after Snail was down-regulated, ZEB1 may regulate epithelial genes in several tumor cell lines...
  61. ncbi Down-regulation of leucocyte immunoglobulin-like receptor expression in the synovium of rheumatoid arthritis patients after treatment with disease-modifying anti-rheumatic drugs
    O A Huynh
    Inflammatory Diseases Research Unit, Wallace Wurth Building, University of New South Wales, Sydney 2052, Australia
    Rheumatology (Oxford) 46:742-51. 2007
  62. pmc Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice
    Rui Hong Wang
    Genetics of Development and Disease Branch, 10 9N105, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Cell 14:312-23. 2008
    ..Finally, we show that many human cancers exhibit reduced levels of SIRT1 compared to normal controls. Thus, SIRT1 may act as a tumor suppressor through its role in DNA damage response and genome integrity...
  63. pmc Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth
    Xiaohong Wang
    HIV and AIDS Malignancy Branch, Center for Cancer Research, Nation Cancer Institute National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 3:e2557. 2008
    ..When introduced into cell lines, miR-146a was found to promote cell proliferation. Collectively, our data indicate that downregulation of miR-143 and miR-145 and upregulation of miR-146a play a role in cervical carcinogenesis...
  64. ncbi p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression
    Tongxiang Lin
    Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0322, USA
    Nat Cell Biol 7:165-71. 2005
    ..These findings indicate an alternative mechanism for p53 to maintain genetic stability in ESCs, by inducing the differentiation of ESCs into other cell types that undergo efficient p53-dependent cell-cycle arrest and apoptosis...
  65. ncbi The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras
    Izumi Oinuma
    Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Science 305:862-5. 2004
    ..Thus, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras...
  66. pmc Changes in gene expression during pegylated interferon and ribavirin therapy of chronic hepatitis C virus distinguish responders from nonresponders to antiviral therapy
    Milton W Taylor
    Department of Biology, Indiana University, Bloomington, IN 47401, USA
    J Virol 81:3391-401. 2007
    ..No specific regulatory gene could be identified as responsible for this global blunting or the racial differences...
  67. pmc DNA damage is a prerequisite for p53-mediated proteasomal degradation of HIF-1alpha in hypoxic cells and downregulation of the hypoxia marker carbonic anhydrase IX
    Milota Kaluzova
    Department of Microbiology and Molecular Genetics, University of California at Irvine, College of Medicine, Irvine 92717, USA
    Mol Cell Biol 24:5757-66. 2004
    ..A model outlining the quantitative relationship between p53, HIF-1alpha, and CAIX is presented...
  68. doi Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells
    Y Saito
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku ku, Tokyo, Japan
    Oncogene 28:2738-44. 2009
  69. ncbi MAP kinase cascade is required for p27 downregulation and S phase entry in fibroblasts and epithelial cells
    N Rivard
    Groupe du Conseil de Recherches Médicales sur le Développement Fonctionnel et la Physiopathologie du Tube Digestif, Département d Anatomie et Biologie Cellulaire, Quebec J1H 5N4, Canada
    Am J Physiol 277:C652-64. 1999
    ..These data indicate that activation of the MAP kinase cascade is required for S phase entry and p27(Kip1) downregulation in fibroblasts and epithelial cells...
  70. ncbi Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL tyrosine phosphatases
    Sean R Werner
    Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202 5132, USA
    Cancer Lett 202:201-11. 2003
    ..We conclude that PRL phosphatases increase cell proliferation by stimulating progression from G1 into S phase, and this process may be dependent on the down regulation of the cyclin dependent kinase inhibitor p21(Cip1/Waf1).
  71. ncbi Down-regulation and antiproliferative role of C/EBPalpha in lung cancer
    Balazs Halmos
    Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cancer Res 62:528-34. 2002
    ..Genetic analysis of the C/EBPalpha gene is in progress to fully evaluate its role as a novel tumor suppressor in lung cancer...
  72. ncbi Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis
    L M Duncan
    Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Cancer Res 58:1515-20. 1998
    ..The expression pattern observed suggests that loss of melastatin expression is an indicator of melanoma aggressiveness...
  73. pmc The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity
    K Aigner
    Max F Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, Vienna, Austria
    Oncogene 26:6979-88. 2007
    ..In invasive ductal and lobular breast cancer, upregulation of ZEB1 was stringently coupled to cancer cell dedifferentiation. Our data show that ZEB1 represents a key player in pathologic EMTs associated with tumour progression...
  74. doi Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth
    Y H Zhao
    Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
    Oncogene 28:3689-701. 2009
    ..This pathway may have a major role in regulating glucose metabolism in breast cancer cells. These novel findings have important implications for the design of new approaches to target ErbB2-overexpressing breast cancers...
  75. doi The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms
    Federica Felicetti
    Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanita, Rome, Italy
    Cancer Res 68:2745-54. 2008
  76. ncbi Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP
    Qinghong Zhang
    Vollum Institute, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, Portland, OR 97239, USA
    Cell 115:177-86. 2003
    ..Finally, reduction in CtBP levels, either by genetic knockout or siRNA, promoted apoptosis in p53-deficient cells. These findings provide a pathway for UV-induced apoptosis in cells lacking p53...
  77. ncbi c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription
    Azadeh Arabi
    Södertörns högskola, S 141 89 Huddinge, Sweden
    Nat Cell Biol 7:303-10. 2005
    ..These results suggest that c-Myc coordinates the activity of all three nuclear RNA polymerases, and thereby plays a key role in regulating ribosome biogenesis and cell growth...
  78. pmc The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
    Adrian P Bracken
    Centre for Epigenetics, Biotech Research and Innovation Centre BRIC, University of Copenhagen, Copenhagen 2200, Denmark
    Genes Dev 21:525-30. 2007
    ..These results provide a model for how the INK4A-ARF locus is activated and how Polycombs contribute to cancer...
  79. pmc Specific down-modulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformation
    Claudio Talora
    Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Genes Dev 16:2252-63. 2002
  80. ncbi A nutrient sensor mechanism controls Drosophila growth
    Julien Colombani
    Institute for Signaling, Developmental Biology and Cancer Research, UMR6543 CNRS Parc Valrose, 06108, Cedex 2, Nice, France
    Cell 114:739-49. 2003
    ..Our results demonstrate that the fat body functions as a nutrient sensor that restricts global growth through a humoral mechanism...
  81. pmc AMSH is an endosome-associated ubiquitin isopeptidase
    John McCullough
    Physiological Laboratory, University of Liverpool, Crown St, Liverpool, L69 3BX, UK
    J Cell Biol 166:487-92. 2004
    ..We propose that AMSH is a deubiquitinating enzyme with functions at the endosome, which oppose the ubiquitin-dependent sorting of receptors to lysosomes...
  82. ncbi Characterization of the murine macrophage mannose receptor: demonstration that the downregulation of receptor expression mediated by interferon-gamma occurs at the level of transcription
    N Harris
    Division of Hematology Oncology, Children s Hospital, Boston, MA 02115
    Blood 80:2363-73. 1992
    ..Therefore, the regulation of mannose receptor expression by IFN-gamma provides a novel system in which to study the mechanisms by which this cytokine represses gene expression...
  83. pmc Modulation of docetaxel-induced apoptosis and cell cycle arrest by all- trans retinoic acid in prostate cancer cells
    A Nehme
    Department of Medicine and the Cancer Center, University of California, 9500 Gilman Drive, San Diego, La Jolla, CA 92093 0058, USA
    Br J Cancer 84:1571-6. 2001
  84. ncbi HLA class I antigen down-regulation in primary ovary carcinoma lesions: association with disease stage
    Marco Vitale
    Department of Anatomy, Pharmacology and Forensic Medicine, University of Parma, Italy
    Clin Cancer Res 11:67-72. 2005
    ..To investigate TAP1, TAP2, and HLA class I antigen expression in primary ovarian carcinoma lesions and to assess the clinical significance of defects in the expression of these molecules...
  85. pmc The activity of the epithelial sodium channels is regulated by caveolin-1 via a Nedd4-2-dependent mechanism
    Il Ha Lee
    Discipline of Physiology, The Bosch Institute, Faculty of Medicine, University of Sydney, New South Wales, Australia
    J Biol Chem 284:12663-9. 2009
    ..Taken together, our data suggest that Cav-1 inhibits the activity of ENaC by decreasing expression of ENaC at the cell membrane via a mechanism that involves the promotion of Nedd4-2-dependent internalization of the channel...
  86. pmc Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation
    Lorenzo F Sempere
    Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA
    Genome Biol 5:R13. 2004
    ..lin-4, let-7 and other miRNA genes are conserved in mammals, and their potential functions in mammalian development are under active study...
  87. ncbi Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma
    Amie Y Lee
    Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA
    Oncogene 23:6672-6. 2004
    ..Our results suggest that methylation silencing of SFRPs may be one of the important mechanisms of aberrant Wnt signaling activation in MM...
  88. ncbi Synergistic tumor suppression by coexpression of FUS1 and p53 is associated with down-regulation of murine double minute-2 and activation of the apoptotic protease-activating factor 1-dependent apoptotic pathway in human non-small cell lung cancer cells
    Wu Guo Deng
    Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 67:709-17. 2007
  89. pmc Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release
    Charles Langelier
    Department of Biochemistry, 15 N Medical Drive East, Room 4100, University of Utah School of Medicine, Salt Lake City, UT 84112 5650, USA
    J Virol 80:9465-80. 2006
    ..These observations indicate that there are probably multiple pathways for protein sorting/MVB vesicle formation in human cells and that HIV-1 does not utilize an ESCRT-II-dependent pathway to leave the cell...
  90. pmc Down-regulation of c-Myc following MEK/ERK inhibition halts the expression of malignant phenotype in rhabdomyosarcoma and in non muscle-derived human tumors
    Francesco Marampon
    Department of Experimental Medicine, University of L Aquila, L Aquila, Italy
    Mol Cancer 5:31. 2006
  91. pmc Natural killer cells in HIV-1 infection: dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates
    Domenico Mavilio
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 100:15011-6. 2003
    ..This phenomenon is not attributed to a direct HIV-1 infection of NK cells; thus, this study may provide insight into the mechanisms of impaired host defenses in HIV-1 viremic patients...
  92. ncbi Suppression of human selenium-binding protein 1 is a late event in colorectal carcinogenesis and is associated with poor survival
    Hyunki Kim
    Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
    Proteomics 6:3466-76. 2006
    ..Our findings indicate that suppression of SELENBP1 is a frequent and late event in colorectal carcinogenesis, and may contribute to the rapid progression of colorectal carcinoma...
  93. ncbi Murine ileitis after intracellular parasite infection is controlled by TGF-beta-producing intraepithelial lymphocytes
    D Buzoni-Gatel
    Laboratoire Associe Institut National de la Recherche Agronomique d'Immunologie Parasitaire, Faculte de Pharmacie, Tours, France
    Gastroenterology 120:914-24. 2001
    ..CONCLUSIONS: Regulation of the ileal inflammatory process resulting from T. gondii is dependent on TGF-beta-producing IELs. The IELs are an essential component in gut homeostasis after oral infection with this parasite...
  94. ncbi The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis
    Igor Garkavtsev
    Edwin L Steele Laboratory for Tumour Biology, Department of Radiation Oncology Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 428:328-32. 2004
    ..These results indicate that ING4 has an important role in brain tumour pathogenesis...
  95. ncbi Wnt signaling in hepatocellular carcinoma: analysis of mutation and expression of beta-catenin, T-cell factor-4 and glycogen synthase kinase 3-beta genes
    Jian Cui
    Liver Cancer Institute, Medical Center of Fudan University, Shanghai, China
    J Gastroenterol Hepatol 18:280-7. 2003
    ..The goal of the present study was to investigate the mechanism of inappropriate activation of the Wnt pathway in hepatocarcinogenesis...
  96. ncbi Inhibition of NF-kappa B by S-nitrosylation
    H E Marshall
    Department of Medicine and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Biochemistry 40:1688-93. 2001
    ..Further, an increase in S-nitrosylated p50 was detected in cells, and the level was modulated by TNFalpha. Taken together, these data suggest that S-nitrosylation of p50 is a physiological mechanism of NF-kappaB regulation...
  97. ncbi Pdcd4 suppresses tumor phenotype in JB6 cells by inhibiting AP-1 transactivation
    Hsin Sheng Yang
    Gene Regulation Section, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
    Oncogene 22:3712-20. 2003
    ..Thus, Pdcd4 suppresses tumor phenotype by inhibiting AP-1-dependent transcription, possibly through inhibiting c-Jun and c-Fos activation...
  98. ncbi RNA helicase A is necessary for translation of selected messenger RNAs
    Tiffiney Roberts Hartman
    Center for Retrovirus Research and Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210 USA
    Nat Struct Mol Biol 13:509-16. 2006
    ..Our results reveal a previously unidentified role for RHA in translation and implicate RHA as an integrative effector in the continuum of gene expression from transcription to translation...
  99. ncbi The IL-4 rapidly produced in BALB/c mice after infection with Leishmania major down-regulates IL-12 receptor beta 2-chain expression on CD4+ T cells resulting in a state of unresponsiveness to IL-12
    H Himmelrich
    World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland
    J Immunol 161:6156-63. 1998
    ..major is primarily based on an up-regulation of IL-4 production, which secondarily induces extinction of IL-12 signaling...
  100. ncbi Analysis of the expression of cell cycle regulators in Ewing cell lines: EWS-FLI-1 modulates p57KIP2and c-Myc expression
    L Dauphinot
    INSERM U509, , Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
    Oncogene 20:3258-65. 2001
    ..These results suggest that the modulation of p57(KIP2) expression by EWS-FLI-1 is a fundamental step in Ewing tumorigenesis...
  101. pmc Persistent down-regulation of Fli1, a suppressor of collagen transcription, in fibrotic scleroderma skin
    Masahide Kubo
    Division of Rheumatology and Immunology and the Laboratory of Cancer Genomics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Am J Pathol 163:571-81. 2003
    ..Persistent down-regulation of Fli1 in scleroderma fibroblasts in vivo may directly contribute to uncontrolled matrix deposition in scleroderma skin...

Research Grants116 found, 100 shown here

  1. Novel TIRF microscopy analyzing trafficking & signaling at the cell cortex
    Derek Toomre; Fiscal Year: 2009
    ..Consistent with the recovery act's goal, this funding will provide full-time summer employment for 4 undergraduate students and accelerate scientific achievement of the parent DP2 award...
  2. Pyruvate Dehydrogenase kinase as Therapeutic Target for Hepatic Steatosis, Obesit
    Robert A Harris; Fiscal Year: 2012
    ..First, down regulation of the expression of PDKs is a critical component of the mechanism by which insulin controls blood glucose...
  3. The gastric X/A-like (ghrelin) cell: A peripheral regulator of food intake
    NILS WG LAMBRECHT; Fiscal Year: 2012
    ..nutrient exposure of the X/A-like cell may result in a rapid down-regulation of ghrelin release and in down regulation of expression or enzymatic activity of the acylating enzyme of ghrelin, GOAT...
    Enrique A Mesri; Fiscal Year: 2013
    ..So our work will allow us to not only to identify mechanisms of KS carcinogenesis but also will help to identify potential new target and new drugs for anti-KS therapy. ..
  5. The role of Fli1 in T cell function and the pathogenesis of lupus
    Tamara K Nowling; Fiscal Year: 2011
    ..Additionally, insight will be gained into the regulation of T cell function in both health and disease with relevance to an array of immune and neoplastic diseases. ..
  6. Lung Lysyl Oxidase Regulation by Metal Ion Homeostasis
    Wande Li; Fiscal Year: 2013
    ..The outcomes of the proposed research are expected to enhance our understanding of mechanisms of LO gene silence by Cd providing the basis for developing prophylaxis and treatment strategies for Cd-related lung diseases. ..
    Melanie H Cobb; Fiscal Year: 2012
    ..Nedd4-2 induces down regulation of a number of membrane proteins including ENaC;this results in reduced sodium reabsorption...
  8. Mechanisms of action of ghrelin in muscle and adipose tissue in cancer-related ca
    Jose M Garcia; Fiscal Year: 2013
    ..Cachexia is also a complication of many other conditions including lung and heart disease and aging, the knowledge generated through this proposal also will help us in establishing new therapies for these conditions. ..
  9. Translational Machinery in Stress Signaling and Tumor Suppression
    THOMAS J contact BEGLEY; Fiscal Year: 2010
    ..The long term potential of the proposed research is significant, as understanding the mechanisms by which TRM9 inhibits tumor growth may provide novel therapeutic opportunities to restore growth-restricting programs in cancer cells. ..
  10. Iron, Metabolic Regulation and Type 2 Diabetes Risk
    Donald A McClain; Fiscal Year: 2013
    ..We show that the acute down regulation of hepcidin by glucose allows increased iron absorption, but the consequences of chronic regulation are not ..
  11. Mechanisms of hepcidin effects in the anemia of chronic disease
    Robert T Means; Fiscal Year: 2013
    ..The proposed studies can potentially lead to an enhanced understanding of the mechanisms of ACD, and therefore to more effective therapy. ..
  12. Mitochondrial Dysfunction and Adipose Insulin Resistance
    David A Bernlohr; Fiscal Year: 2013
    ..this oxidative stress challenge are new findings that describe the tumor necrosis factor 1 (TNF1) dependent down regulation of glutathione S-transferase A4 setting the stage for a molecular cascade of events that activates the c-JUN ..
  13. Prostate cancer chemoprevention by penta-galloyl-glucose
    Junxuan Lu; Fiscal Year: 2013
    ..the Stat3 oncogenic signaling, associated with cyclin D1 (cell cycle) and Bcl-xL/Mcl-1 (cell survival) down regulation. Furthermore, PGG significantly inhibited the in vivo growth of human DU145 PCa xenografts in nude mice ..
  14. Role of Diabetes in Development of Renal Cell Carcinoma
    SAMY LEWIZ HABIB; Fiscal Year: 2013
  15. Molecular Mechanisms of Parvovirus Gene Expression and Replication
    Jianming Qiu; Fiscal Year: 2013
    ..e., EPCs ex vivo-expanded under hypoxic conditions for B19V in this application. ..
  16. The Kallikrein/Kinin-Mast Cell Interaction in Volume Overload
    CHIH CHANG KEVIN WEI; Fiscal Year: 2013
  17. Regulation of myocardial growth and death by GSK-3
    Junichi Sadoshima; Fiscal Year: 2013
    ..The knowledge obtained from this investigation should be useful for the development of better treatment for heart failure, ischemic injury and stem cell therapy. ..
  18. Protein Nitration in the Placenta
    Leslie Myatt; Fiscal Year: 2012
  19. Immune Mechanism of Rejection in Human Lung Allografts
    Thalachallour Mohanakumar; Fiscal Year: 2013
    ..risk factor for the development of BOS the first goal of this application is to test the hypothesis that down regulation of pre-existing autoimmunity to self-Ags prior to LTx will abrogate interactions between pre-existing Abs to ..
  20. Bisphosphonates in the treatment of chronic kidney disease-mineral bone disease
    Sharon M Moe; Fiscal Year: 2013
    ..Newer bisphosphonates such as zoledronic acid also inhibit angiogenesis through down regulation of vascular endothelial growth factor (VEGF)...
  21. Targeting iNOS to inhibit myeloid-derived suppressor cells (MDSC) in melanoma
    ANDREW GREGORY SIKORA; Fiscal Year: 2013
    ..L-nil treatment was also associated with down regulation of activated STAT3 in the tumor, and normalization of elevated levels of VEGF and other inflammatory ..
  22. Parathyroid Hormone & Vitamin D Effects on Salt Sensitivity and Vascular Function
    ANNA LIZA BELEN VALINA TOTH; Fiscal Year: 2010
    ..such as vasoconstriction, activation of fibroblasts, insulin resistance, dyslipidemia, fat deposition and down regulation of endothelial nitric oxide - all of which plausibly contribute to elevated blood pressure (BP)and vascular ..
  23. DNA Methylation in Ethanol Drinking Behavior
    David P Gavin; Fiscal Year: 2013
    ..Ultimately, these studies will identify novel molecular targets in the actions of ethanol and ethanol drinking behavior, and promote the development of pharmacotherapy for alcoholism. ..
  24. Alzheimer's Disease Therapeutic
    Trevor P Castor; Fiscal Year: 2012
    ..Alternatively, at this stage, Amylon will merge with a mid-tier public company or be acquired by a multinational pharmaceutical company. ..
  25. Iron-Induced Changes in Liver That Predispose to Malignancy
    Harriet C Isom; Fiscal Year: 2010
  26. Roles for microRNA-122 in hepatitis C virus RNA amplification
    Peter Sarnow; Fiscal Year: 2013
    ..5 fold drop in viral load without any emergence of resistant virus (Lanford et al. 2010. Science: 327:198-201). ..
  27. Nitric Oxide in Hemodialysis AV Fistula Maturation
    Richard A Cohen; Fiscal Year: 2010
  28. Understanding Pain of Gastrointestinal Origin in Women that Serve in OEF/OIF
    Beverley Greenwood-Van Meerveld; Fiscal Year: 2013
    ..that MR/GR expression in the amygdala is abnormal in adult rats following ELS, We will also determine whether down regulation of GR or MR in the CeA using antisense oligodeoxynucleotides (ODNs) affects anxiety and colonic ..
    Raymond F Novak; Fiscal Year: 2010
  30. Mechanisms and Consequences of Reduced PPAR gamma in Pulmonary Hypertension
    C Michael Hart; Fiscal Year: 2013
    ..The results of this proposal can thereby define novel and effective therapeutic strategies to regulate programs of gene expression involved in PH pathogenesis. ..
  31. Mitochondrial Dysfunction and Adipose Insulin Resistance
    DAVID BERNLOHR; Fiscal Year: 2009
    ..challenge are new findings that describe the tumor necrosis factor [unreadable] (TNF[unreadable]) dependent down regulation of glutathione S-transferase A4 setting the stage for a molecular cascade of events that activates the c-JUN ..
  32. Role of GDNF in the regulation of hepatic steatosis
    SHANTHI K SRINIVASAN; Fiscal Year: 2013
    ..Identification of new therapies for hepatic steatosis will directly benefit the veteran population. Taken together our data from this proposal may provide novel targets for the treatment or prevention of hepatic steatosis. ..
  33. Impaired mitochondrial fusion in pulmonary arterial hypertension
    Stephen L Archer; Fiscal Year: 2010
    ..This proposal seeks to understand the role of the HIF-1a and mitofusin in PAH and develop therapies (inhibition of HIF-1 a and supplementation of mitofusin-2) to restore mitochondrial form and function and cure PAH. ..
  34. Role of MicroRNA mi R-33 in Controlling Cholesterol/Lipid Homeostasis
    Anders M Naar; Fiscal Year: 2010
    ..These studies should provide novel therapeutic strategies aimed at increasing HDL synthesis and cholesterol clearance in patients with cardiovascular disease. ..
  35. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  36. Novel Zebrafish Models to Study Toxicity of PCBs and Pesticides During Pregnancy
    Lisa Satterwhite; Fiscal Year: 2009
    ..In Aim 1, we test the hypothesis that PCB-126 or chlorpyrifos activated AHR leads to down regulation of tbx5 followed by p53 mediated cell cycle arrest in the heart by using genetic epistasis and DNA microarray ..
  37. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
  38. Vitamin A adjuvant to enhance gut immunity and rotavirus vaccines in neonates
    Linda J Saif; Fiscal Year: 2010
    ..Vitamin A adjuvants may be universally applicable, not only to rotavirus vaccines, but also to other mucosal vaccines for humans such as HIV. ..
  39. Regulation of Astrocyte TIMP-1 in HIV-Associated Dementia
    JEREL ADAM FIELDS; Fiscal Year: 2011
    ..Thus, we propose that down regulation of astrocyte TIMP-1 during HAD is mediated through differential transcriptional regulation via a CAAT site in ..
  40. Maternal nutrient restriction and nonhuman primate fetal skeletal muscle developm
    Min Du; Fiscal Year: 2010
  41. Epigenetic downregulation of the antibody response and inhibition of autoimmunity
    Paolo Casali; Fiscal Year: 2013
  42. Mechanism(s) of Hepatocyte Transformation by the Hepatitis B Virus X Protein
    Ourania M Andrisani; Fiscal Year: 2013
    ..Plk1 inhibitors are in clinical trials for other types of cancer and could serve as therapy for HBV-HCC. Our studies hold promise to reveal novel therapy targets and biomarkers for HBV-HCC. ..
  43. Histamine modulation of biliary proliferation and damage
    Heather L Francis; Fiscal Year: 2013
    ..synthesis may be important in the inhibition of biliary hyperplasia, overexpression of HDC (leading to enhanced histamine release) may be key for stimulating biliary proliferation in ductopenic conditions associated with biliary damage ..
  44. Validation of microRNAs as therapeutic targets in hematological malignancies
    Natarajan Muthusamy; Fiscal Year: 2013
    ..Therefore, we propose here to replace the low levels of natural microRNAs in leukemia cells with synthetic microRNAs as novel therapeutic approach to leukemia patients. ..
  45. Transgenerational effects of maternal high fat diet during pregnancy on breast ca
    Leena A Hilakivi-Clarke; Fiscal Year: 2013
  46. Myosin phosphatase autoinhibition in gastrointestinal smooth muscle contraction
    Avril V Somlyo; Fiscal Year: 2012
    ..whether non-telokin mediated attenuation of the autoinhibition by cyclic nucleotides occurs through down regulation of RhoA activity by Epac activation of Rap1, through phosphorylation of Ser695 of MYPT1 or inhibitory ..
  47. MicroRNAs in the Progression and Metastisis of Prostate Cancer
    Rajvir Dahiya; Fiscal Year: 2013
    ..In the future, these results may provide better strategies for the management of prostate cancer. ..
  48. Ionic currents in gastrointestinal smooth muscle
    Hamid I Akbarali; Fiscal Year: 2013
    ..Determining the mechanisms of altered protein-protein interaction between ion channels and intracellular signaling molecules are likely to define novel therapeutic approaches targeted at ion channels ..
  49. Adult and Transgenerational Toxicity Due to Developmental TCDD Exposure
    Tracie R Baker; Fiscal Year: 2013
    ..The University of Wisconsin has numerous NIH-sponsored training programs, core facilities and funded researchers making it an ideal training environment for me to develop as an independent scientist. ..
  50. Maternal Obesity affects AMP-Kinase in Muscle Cell Differentiation
    Min Du; Fiscal Year: 2013
  51. Regulation of Human Papillomavirus Replication via Cell Signaling Pathways
    ANASTACIA GRIEGO; Fiscal Year: 2013
    ..Specific Aims are designed to determine if initiating a break in EGFR-pathway signaling will result in down regulation of HPV activities in infected cells, leading to recovered p53 and pRb activity, which could render cells more ..
  52. Early social stress, novelty seeking, and impulsive behavior
    David M Lyons; Fiscal Year: 2013
    ..Consequently, there is an urgent need for new mechanistic insights to guide the development of public health policies and interventions designed to alleviate the detrimental long-term effects of exposure to early social stress. ..
  53. Nanoelectrode arrays for study of the molecular mechanisms, triggers, and inhibit
    Peter J Burke; Fiscal Year: 2012
    ..pathway, induction of hexokinase II, alteration an adenine nucleotide translocator (ANT) isoform expression, down regulation of the SOC2 cytochrome c oxidase (complex IV, COX) assembly factor, mutation in mitochondrial DNA (mtDNA) ..
  54. Role of microRNA-122 in hepatocarcinogenesis using conditional knock out mice
    Kalpana Ghoshal; Fiscal Year: 2013
    ..Using an animal model for hepatocarcinogenesis we were the first to demonstrate down regulation of miR-122, the most abundant liver-specific microRNA (~70% of the total miRNA) in the liver, during the ..
  55. Role of natural indoles in experimental autoimmune encephalomyelitis
    Mitzi Nagarkatti; Fiscal Year: 2013
    ..These studies should provide novel insights into the basic mechanisms through which plant indoles exhibit anti- inflammatory properties so that they can be used against a wide range of autoimmune and inflammatory diseases. ..
    ANIL KUMAR JAISWAL; Fiscal Year: 2013
    ..revealed that NQO1 and NQO2 stabilization of tumor suppressor p53 against 20S proteasome degradation and down regulation of p63 and MAPK pathway contributed to carcinogenesis...
  57. Mechanism of CREB dysregulation in Alzheimer brain
    Subbiah Pugazhenthi; Fiscal Year: 2013
    ..Our lab has 15 years of experience and the expertise to examine CREB function in the context of parallel activation of competing transcription factors during inflammation and oxidative stress. ..
  58. Regulation/Role of AcylCer in Normal Epidermis and Atopic Dermatitis
    Peter M Elias; Fiscal Year: 2013
  59. Klotho regulation and aging
    Gwendalyn D King; Fiscal Year: 2010
    ..The aging suppressor protein, Klotho is decreased in the brain with age and may be a target for therapeutic development against neurodegenerative disorders. ..
  60. Aberrant DNA Methylation of MicroRNA Genes in Hepatocellular Carcinoma (HCC)
    Jing Shen; Fiscal Year: 2012
    ..PHS 398/2590 (Rev. 06/09) Page Continuation Format Page ..
  61. Mechanisms in transcriptional regulation during cardiac hypertrophy
    Maha Abdellatif; Fiscal Year: 2013
    ..2) Determine the role of TFIIB in gene transcription and the development of cardiac hypertrophy. 3) Determine the role of Cdk9 in gene transcription and the development of cardiac hypertrophy. ..
  62. CNS Demyelinating Autoimmunity Targeting Water Channel Complexes
    SEAN JOSEPH PITTOCK; Fiscal Year: 2013
  63. Role of the insulin/IGF-axis in incident CIN-2+
    Howard D Strickler; Fiscal Year: 2010
  64. Pulmonary Vascular-Right Ventricular Axis Research Program
    Wai Hong Wilson Tang; Fiscal Year: 2013
    ..We test this hypothesis PAEC derived from patients'lungs, explanted human hearts, and in a mechanistic longitudinal study of ?AR blockade in PAH patients. ..
  65. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2013
    ..abstract_text> ..
    Michael Levin; Fiscal Year: 2013
    ..The combination of both a diagnostic and pathogenic immune reaction is of particular relevance and has the potential to make important contributions to the long- term care and outcomes of people with MS. ..
  67. Effect of preimplantation embryo culture on adult glucose homeostasis
    Paolo Rinaudo; Fiscal Year: 2013
    ..Knowledge gained from this research may lead to novel understanding of the mechanisms used by the embryo to sense and to adapt to different environments. ..
    Nancy M Hollingsworth; Fiscal Year: 2013
    ..The knowledge gained from these studies is likely to be relevant to mammals, given the evolutionary conservation of meiosis between yeast and mammals. ..
  69. The role of regulatory T cells in biliary atresia
    Alexander Miethke; Fiscal Year: 2013
  70. Epigenic Control of ENaC Transcription and Sodium Transport
    Wenzheng Zhang; Fiscal Year: 2013
  71. Crosstalk between estrogen and bile acid signaling pathway
    Ruitang Deng; Fiscal Year: 2013
    ..Understanding the mechanisms and pathological consequences will provide a molecular basis to develop new drugs to treat or prevent those diseases. ..
  72. Bmi-1, a potential therapeutic target in ovarian cancer
    Resham Bhattacharya; Fiscal Year: 2013
    ..The proposed studies will validate Bmi-1 as an important new target using readily translatable nanoliposomal delivery methods with potential for therapy even in chemoresistant ovarian cancer. ..
  73. Role of Beta Spectrin and Smad in Alcohol Induced Liver and GI Cell Proliferation
    Lopa Mishra; Fiscal Year: 2013
    ..c) Expand to fine mapping. Significantly, studies proposed under this application should provide the scientific community with a new understanding of the instrumental regulators in alcohol induced liver injury and neoplasia. ..
  74. Immune activation by cetuximab in head and neck cancer patients
    Robert L Ferris; Fiscal Year: 2013
    ..abstract_text> ..
  75. Molecular probes for a vOTU from CCHFV using a fluorogenic peptide
    SCOTT DUSAN PEGAN; Fiscal Year: 2013
  76. Mouse model for eyelid disease: Congenital blepharophimosis
    Chia Yang Liu; Fiscal Year: 2013
    ..We will also delineate a molecular pathway that leads to the down-regulation of FoxL2 and subsequent malformation of the levator M[unreadable]ellersmooth muscle during embryonic eyelid development (Aim2). ..
    Carol Prives; Fiscal Year: 2013
    ..The projects are even more interdependent and interactive than before and as a result much of the proposed research cannot be done effectively without the support of this program. ..
  78. Antisense oligonucleotides for the treatment of spinocerebellar ataxia type 2
    Daniel R Scoles; Fiscal Year: 2013
    ..The proposed work will break new ground for treatment of neurodegenerative diseases by demonstrating feasibility of targeting dominant-acting mutated polyQ genes with antisense oligonucleotides. ..
    Raj M Lakshman; Fiscal Year: 2013
    ..abstract_text> ..
  80. Connexin 43 in Bone Remodeling
    Roberto Civitelli; Fiscal Year: 2013
    ..Results will establish the mechanisms by which Cx43 modulates cortical bone and how such mechanisms cause the skeletal abnormalities of ODDD, findings that may be translated to clinical settings and lead to pharmacologic targeting. ..
  81. Role of CD98 Glycoprotein in Intestinal Inflammation
    Hamed Laroui; Fiscal Year: 2013
    ..g. DDW and FASEB), and receive guidance from a selected Career Development Research Advisory Committee. ..
  82. Genome maintenance functions of CREB/ATF transcription factors
    RANDAL SCOT TIBBETTS; Fiscal Year: 2013
  83. Innate immune signal transduction specificity in inflammatory disease
    Derek W Abbott; Fiscal Year: 2013
    ..This work aims to help determine the causes of inflammatory disease and aims to identify novel targets for pharmaceutical intervention in these debilitating disorders. ..
  84. The Role of de novo Cytosine DNA Methyltransferases 3a &3b in Gene Methylation
    Ivo Teneng; Fiscal Year: 2013
    ..transformation involving induction of epithelial to mesenchymal transition in HBECs that manifests through down regulation of the microRNA (miR)- 200 family and miR-205, changes in expression of cytosine DNMTs and methylation of ..
  85. Quiescent Tc17 programmed CD8 T cells and their role in graft versus host disease
    CAMERON JOHN TURTLE; Fiscal Year: 2013
    ..abstract_text> ..
  86. Reactive astrogliosis regulates blood-brain barrier permeability.
    Gareth R John; Fiscal Year: 2013
    ..In this proposal, using a conditional knockout approach we will determine the roles of HIF-1a, VEGF-A, CLN-5 and OCLN in BBB disruption, with the goal of identifying novel therapeutic targets to restrict lesion formation in MS. ..
  87. Targeting PCSK9 Transcription to Combat Hypercholesterolemia by Berberine
    Jingwen Liu; Fiscal Year: 2013
    ..obtained new evidence indicating the potential involvement of ubiquitin-proteasome pathway in BBR induced down regulation of HNF1? protein...
  88. Investigation into Cold-induced Pulmonary Vascular Inflammation and Dysfunction
    Zhongjie Sun; Fiscal Year: 2013
    ..The proposed work is significant for people who live in cold regions and who have outside duties in winter. ..
  89. Molecular mechanisms of chemoresistance in breast cancer
    Manabu Kurokawa; Fiscal Year: 2013
    ..Moreover, this work will provide me with the means to establish myself as an independent investigator. ..
  90. Metformin as a novel chemopreventive agent for prostate cancer
    Xin Li; Fiscal Year: 2013
    ..e. those with PIN or high-grade PIN). The novel combined cancer prevention therapy using metformin and mTOR inhibitors proposed in this study may display promising synergistic efficacy and will be translational to clinical application. ..
  91. Regulation and Function of AKAP12A in the Vessel Wall
    Joseph M Miano; Fiscal Year: 2013
    ..We also imagine that information obtained here will have direct applications in other disease contexts where AKAP12A expression and downstream activities are compromised (e.g., cancer). ..
  92. Novel mechanisms for Alzheimer's disease prevention and/or treatment
    Luigi Puglielli; Fiscal Year: 2013
    ..Finally, a combination of biochemical, biophysical, and cellular approaches will be used to assess whether newly identified compounds can serve as additional inhibitory tools (Aim 2B). ..
  93. Identifying New Regulators of Leptin-Like Signaling in Drosophila Brain Neurons
    KAI G ZINN; Fiscal Year: 2013
    ..Negative regulators identified in these experiments might be potential drug targets whose inhibition could upregulate anorexigenic leptin signaling in leptin-resistant obese individuals. ..
  94. Role of miRNA-375 in Invasive Phenotype of Head and Neck Squamous Cell Carcinoma
    Lizandra Jimenez; Fiscal Year: 2013
    ..Functional validation of the phenotypic effects of the down-regulation of putative targets of miR-375 will be performed by siRNA knockdown and rescue of the targets in the transductant cells. ..
  95. Mechanisms of Altered Gastrointestinal Dysfunction
    QiQi Zhou; Fiscal Year: 2013
    ..g. opioid or glutamate receptors) that drive visceral nociception. The ultimate goal of the proposed translational studies is to develop new therapies for treating our patients with IBS and other functional GI disorders. ..
  96. B-RAF Regulation of the Cell Cycle in Melanoma
    Andrew E Aplin; Fiscal Year: 2013
    ..At the completion of our experiments, we aim to have identified new targets for therapeutic intervention to prevent aberrant melanoma cell proliferation. ..
  97. A structure-function analysis of let-7g miRNA regulation by Lin28
    CHRISTINA ROSE MOZES; Fiscal Year: 2012
  98. Lipidoid Nanoparticles with Simultaneous Multi-Gene Regulation for Cancer Therapy
    Yizhou Dong; Fiscal Year: 2013
    ..It is my hope that this platform will enable scientists in the future to fine-tune the combination of siRNA and pDNA for specific disease treatment in specific individuals, thereby advancing the field of personalized medicine. ..
  99. Mitochondrial dysfunction in glaucomatous optic neuropathy
    Won Kyu Ju; Fiscal Year: 2013
    ..abstract_text> ..
  100. Mechanisms of megakaryocyte maturation
    Diane S Krause; Fiscal Year: 2013
    ..In addition, the data obtained will reveal the molecular regulation and functions of MKL1, a transcriptional cofactor in the RhoA/SRF pathway, which is dysregulated in Myelodysplasia (MDS) especially that associated with 5q- syndrome. ..
    Anath Shalev; Fiscal Year: 2013