neurofibromin 1

Summary

Summary: A protein found most abundantly in the nervous system. Defects or deficiencies in this protein are associated with NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome. Mutations in the gene (GENE, NEUROFIBROMATOSIS 1) affect two known functions: regulation of ras-GTPase and tumor suppression.

Top Publications

  1. pmc The NF1 tumor suppressor critically regulates TSC2 and mTOR
    Cory M Johannessen
    Genetics Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 458c NRB, 77 Louis Pasteur Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:8573-8. 2005
  2. ncbi Tumour predisposition in mice heterozygous for a targeted mutation in Nf1
    T Jacks
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139
    Nat Genet 7:353-61. 1994
  3. ncbi The neurofibromatosis 1 gene product neurofibromin regulates pituitary adenylate cyclase-activating polypeptide-mediated signaling in astrocytes
    Biplab Dasgupta
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 23:8949-54. 2003
  4. ncbi The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21
    G A Martin
    Department of Molecular Biology, Cetus Corporation, Emeryville, California 94608
    Cell 63:843-9. 1990
  5. pmc Structural analysis of the GAP-related domain from neurofibromin and its implications
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Dortmund, Germany
    EMBO J 17:4313-27. 1998
  6. ncbi Neurofibromin binds to caveolin-1 and regulates ras, FAK, and Akt
    Madanamohan Boyanapalli
    Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
    Biochem Biophys Res Commun 340:1200-8. 2006
  7. ncbi The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins
    R Ballester
    Cold Spring Harbor Laboratory, New York 11724
    Cell 63:851-9. 1990
  8. ncbi Neurofibromatosis type 1 revisited
    Virginia C Williams
    Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA
    Pediatrics 123:124-33. 2009
  9. pmc A novel bipartite phospholipid-binding module in the neurofibromatosis type 1 protein
    Igor D'Angelo
    European Molecular Biology Laboratory, Structural and Computational Biology Programme, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    EMBO Rep 7:174-9. 2006
  10. pmc Neurofibromin regulation of ERK signaling modulates GABA release and learning
    Yijun Cui
    Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Cell 135:549-60. 2008

Detail Information

Publications232 found, 100 shown here

  1. pmc The NF1 tumor suppressor critically regulates TSC2 and mTOR
    Cory M Johannessen
    Genetics Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 458c NRB, 77 Louis Pasteur Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:8573-8. 2005
    ..Finally, these data suggest that rapamycin, or its derivatives, may represent a viable therapy for NF1...
  2. ncbi Tumour predisposition in mice heterozygous for a targeted mutation in Nf1
    T Jacks
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139
    Nat Genet 7:353-61. 1994
    ..The wild-type Nf1 allele is lost in approximately half of the tumours from heterozygous animals. In addition, homozygosity for the Nf1 mutation leads to abnormal cardiac development and mid-gestational embryonic lethality...
  3. ncbi The neurofibromatosis 1 gene product neurofibromin regulates pituitary adenylate cyclase-activating polypeptide-mediated signaling in astrocytes
    Biplab Dasgupta
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 23:8949-54. 2003
    ..These results demonstrate that neurofibromin positively influences cAMP generation and activation of cAMP growth regulatory targets in astrocytes and expands the role of the NF1 gene in astrocyte growth regulation...
  4. ncbi The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21
    G A Martin
    Department of Molecular Biology, Cetus Corporation, Emeryville, California 94608
    Cell 63:843-9. 1990
    ..However, its specific activity was about 30 times lower. These kinetic measurements suggest that NF1 may be a significant regulator of ras p21 activity, particularly at low ras p21 concentrations...
  5. pmc Structural analysis of the GAP-related domain from neurofibromin and its implications
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Dortmund, Germany
    EMBO J 17:4313-27. 1998
    ....
  6. ncbi Neurofibromin binds to caveolin-1 and regulates ras, FAK, and Akt
    Madanamohan Boyanapalli
    Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
    Biochem Biophys Res Commun 340:1200-8. 2006
    ..These novel findings provide insight into possible signaling mechanisms of Nf1 and suggest that together Nf1 and Cav-1 may coordinately regulate cell growth and differentiation...
  7. ncbi The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins
    R Ballester
    Cold Spring Harbor Laboratory, New York 11724
    Cell 63:851-9. 1990
    ..These studies indicate that the NF1 gene product can interact with RAS proteins and demonstrate structural and functional similarities and differences among the GAP, IRA1, IRA2, and NF1 proteins...
  8. ncbi Neurofibromatosis type 1 revisited
    Virginia C Williams
    Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA
    Pediatrics 123:124-33. 2009
    ..In this review, we describe the clinical manifestations, recent molecular and genetic findings, and current and developing therapies for managing clinical problems associated with neurofibromatosis type 1...
  9. pmc A novel bipartite phospholipid-binding module in the neurofibromatosis type 1 protein
    Igor D'Angelo
    European Molecular Biology Laboratory, Structural and Computational Biology Programme, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    EMBO Rep 7:174-9. 2006
    ..The unique architecture of the domain interface points to a model of how the PH-like domain may regulate binding of a ligand by the Sec14 module...
  10. pmc Neurofibromin regulation of ERK signaling modulates GABA release and learning
    Yijun Cui
    Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Cell 135:549-60. 2008
    ..Importantly, our results also revealed lasting increases in GABA release triggered by learning, indicating that the mechanisms uncovered here are of general importance for learning...
  11. pmc Neurofibromin 1 (NF1) defects are common in human ovarian serous carcinomas and co-occur with TP53 mutations
    Navneet Sangha
    Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109 2200, USA
    Neoplasia 10:1362-72, following 1372. 2008
    ....
  12. pmc Comparative oncogenomics implicates the neurofibromin 1 gene (NF1) as a breast cancer driver
    Marsha D Wallace
    Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
    Genetics 192:385-96. 2012
    ..Chaos3 tumors underwent recurrent copy number alterations (CNAs), particularly deletion of the RAS inhibitor Neurofibromin 1 (Nf1) in nearly all cases. These overlap with human CNAs including NF1, which is deleted or mutated in 27...
  13. pmc Neurofibromin 1 is a miRNA target in neurons
    Maria Paschou
    Molecular and Cellular Neurobiology Lab, Center of Neurosciences and Social Psychiatry, Biomedical Research Foundation, Academy of Athens, Athens, Greece
    PLoS ONE 7:e46773. 2012
    Mutations of the neurofibromin 1 gene cause neurofibromatosis type 1, a disease in which learning and behavioral abnormalities are common. The disease is completely penetrant but shows variable phenotypic expression in patients...
  14. ncbi MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1
    Guolin Chai
    Maine Institute for Human Genetics and Health, Bangor, Maine
    Cancer Sci 101:1997-2004. 2010
    ..These results suggest that miR-10b may play an important role in NF1 tumorigenesis through targeting neurofibromin and RAS signaling...
  15. pmc Neurofibromin physically interacts with the N-terminal domain of focal adhesion kinase
    Frederick Kweh
    University of Florida Shands Cancer Center, Gainesville, Florida, USA
    Mol Carcinog 48:1005-17. 2009
    ..Thus, the results demonstrate the novel interaction of neurofibromin and FAK and suggest their involvement in cell adhesion, cell growth, and other cellular events and pathways...
  16. ncbi The pre-GAP-related domain of neurofibromin regulates cell migration through the LIM kinase/cofilin pathway
    Sigal Starinsky-Elbaz
    Department of Neurobiology, George S Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel
    Mol Cell Neurosci 42:278-87. 2009
    ..Impairment of these cellular functions of neurofibromin provides novel insights into the invasiveness/progression of NF1-associated tumors...
  17. pmc Genetic and cellular evidence of vascular inflammation in neurofibromin-deficient mice and humans
    Elisabeth A Lasater
    Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, 46202, USA
    J Clin Invest 120:859-70. 2010
    ....
  18. ncbi The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae
    G F Xu
    Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City 84132
    Cell 63:835-41. 1990
    ..These results establish that this NF1 domain has ras GAP activity similar to that found with IRA2 protein and mammalian GAP, and therefore may also regulate ras function in vivo...
  19. ncbi Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms
    Balazs Hegedus
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell Stem Cell 1:443-57. 2007
    ..Together, these findings demonstrate that neurofibromin is required for normal glial and neuronal development involving separable Ras-dependent and cAMP-dependent mechanisms...
  20. ncbi The neurofibromatosis type 1 gene product neurofibromin enhances cell motility by regulating actin filament dynamics via the Rho-ROCK-LIMK2-cofilin pathway
    Tatsuya Ozawa
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Japan
    J Biol Chem 280:39524-33. 2005
    ..These findings may explain, in part, the mechanism of multiple neurofibroma formation in NF1 patients...
  21. ncbi Genetic basis of tumorigenesis in NF1 malignant peripheral nerve sheath tumors
    Meena Upadhyaya
    Institute of Medical Genetics, Cardiff University, Heath Park Campus, Cardiff CF14 4XN, United Kingdom
    Front Biosci (Landmark Ed) 16:937-51. 2011
    ..Multidisciplinary collaborative efforts are clearly essential to fully decipher both the complex molecular basis of MPNST development and to define potential therapeutic targets...
  22. pmc Unravelling the genetic basis of variable clinical expression in neurofibromatosis 1
    Audrey Sabbagh
    Faculte des Sciences Pharmaceutiques et Biologiques, UMR745 INSERM, Universite Paris Descartes, Paris 75006, France
    Hum Mol Genet 18:2768-78. 2009
    ..Taken together, our results provided evidence that genetic modifiers, unlinked to the NF1 locus, contribute to the variable expressivity of the disease...
  23. pmc The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells
    Nancy M Joseph
    Center for Stem Cell Biology, Howard Hughes Medical Institute, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 2216, USA
    Cancer Cell 13:129-40. 2008
    ..Tumors appeared to arise from differentiated glia, not NCSCs...
  24. ncbi Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1
    Rui M Costa
    Departments of Neurobiology, Psychiatry and Psychology, BRI, University of California at Los Angeles, Los Angeles, California 90095 1761, USA
    Nature 415:526-30. 2002
    ..Our findings have implications for the development of treatments for learning deficits associated with NF1...
  25. ncbi The neurofibromatosis type 1 gene encodes a protein related to GAP
    G F Xu
    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84132
    Cell 62:599-608. 1990
    ..Mapping of the cDNA clones has confirmed that NF1 spans a t(1;17) translocation mutation and that three active genes lie within an intron of NF1, but in opposite orientation...
  26. ncbi The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes
    M M Daston
    Department of Anatomy and Cell Biology, University of Cincinnati College of Medicine, Ohio 45267 0521
    Neuron 8:415-28. 1992
    ..Some NF1 disease manifestations, such as Schwann cell tumors and learning disabilities, may result from abnormalities in the cells that express neurofibromin...
  27. ncbi Phosphorylation of neurofibromin by PKC is a possible molecular switch in EGF receptor signaling in neural cells
    D Mangoura
    Department of Pediatrics, The University of Chicago, Chicago, IL, USA and Neurosciences Division, Institute for Biomedical Research, Athens, Greece
    Oncogene 25:735-45. 2006
    ..Our data may suggest a novel mechanism for regulating biological responses to EGF and provide a new aspect for the understanding of the aberrant proliferation seen in the CNS of children with NF1...
  28. ncbi The neurofibromin 1 type I isoform predominance characterises female population affected by sporadic breast cancer: preliminary data
    Daniel Marrero
    Laboratorio de Oncogenomica, Unidad de Investigacion Medica en Enfermedades Oncologicas, Hospital de Oncologia, CMN SXXI, IMSS, Mexico, D F
    J Clin Pathol 65:419-23. 2012
    b>Neurofibromin 1 (NF1) as a tumour suppressor gene can give rise to several transcripts by an alternative splicing event, generated at least for CELF cofactors...
  29. ncbi Molecular diagnosis of neurofibromatosis type 1: 2 years experience
    Sian Griffiths
    Institute of Medical Genetics, University Hospital of Wales, Cardiff CF14 4XN, UK
    Fam Cancer 6:21-34. 2007
    ....
  30. ncbi Germline and somatic NF1 gene mutation spectrum in NF1-associated malignant peripheral nerve sheath tumors (MPNSTs)
    M Upadhyaya
    Institute of Medical Genetics, Cardiff University, Cardiff, United Kingdom
    Hum Mutat 29:74-82. 2008
    ..DNA from 20 tumors showed evidence for loss of heterozygosity (LOH) across the TP53 region in 11 samples, with novel TP53 point mutations in four tumors...
  31. ncbi Neurofibromin as a regulator of melanocyte development and differentiation
    Ganesh Diwakar
    Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    J Cell Sci 121:167-77. 2008
    ....
  32. ncbi Analysis of melanocyte precursors in Nf1 mutants reveals that MGF/KIT signaling promotes directed cell migration independent of its function in cell survival
    B Wehrle-Haller
    Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403 1254, USA
    Dev Biol 232:471-83. 2001
    ..We further suggest that the MGF mediates MP migration through a signaling pathway that does not involve RAS...
  33. ncbi Phenotypic reversion of invasive neurofibromin-deficient schwannoma by FTS: Ras inhibition reduces BMP4/Erk/Smad signaling
    Batya Barkan
    Department of Neurobiology, The George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    Mol Cancer Ther 10:1317-26. 2011
    ..Our results support the therapeutic potential of FTS, in conjuncture with BMP and TGF-β pathway inhibitors, toward the inhibition of mitogenic and morphogenic signaling pathways and the alleviation of NF1 symptoms...
  34. ncbi Neurofibromatosis type 1 (NF1) tumor suppressor, neurofibromin, regulates the neuronal differentiation of PC12 cells via its associating protein, CRMP-2
    Siriporn Patrakitkomjorn
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University School of Medicine, Kumamoto, Japan
    J Biol Chem 283:9399-413. 2008
    ....
  35. ncbi Mouse models of tumor development in neurofibromatosis type 1
    K Cichowski
    Department of Biology and Center for Cancer Research and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 286:2172-6. 1999
    ..These two mouse models provide the means to address fundamental aspects of disease development and to test therapeutic strategies...
  36. pmc Does cognitive impairment explain behavioral and social problems of children with neurofibromatosis type 1?
    Stephan C J Huijbregts
    Department of Education and Child Studies, Clinical Child and Adolescent Studies, Leiden Institute for Brain and Cognition, Leiden University, The Netherlands
    Behav Genet 41:430-6. 2011
    ....
  37. ncbi Recent insights into bone development, homeostasis, and repair in type 1 neurofibromatosis (NF1)
    Aaron Schindeler
    Department of Orthopaedic Research and Biotechnology, The Children s Hospital at Westmead, Sydney, Australia
    Bone 42:616-22. 2008
    ..This paper reviews the current literature on NF1 bone development, homeostatic regulation, and repair, and highlights some emerging themes that may have relevance for managing orthopaedic disorders that can arise in individuals with NF1...
  38. ncbi Neurofibromatosis type 1 protein and amyloid precursor protein interact in normal human melanocytes and colocalize with melanosomes
    Sofie De Schepper
    Department of Dermatology, Ghent University Hospital, Ghent, Belgium
    J Invest Dermatol 126:653-9. 2006
    ..We suggest that a complex between amyloid precursor protein, neurofibromin, and melanosomes might be important in melanosome transport, which could shed a new light on the etiopathogenesis of pigment-cell-related manifestations in NF1...
  39. pmc Valosin-containing protein and neurofibromin interact to regulate dendritic spine density
    Hsiao Fang Wang
    Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
    J Clin Invest 121:4820-37. 2011
    ..The data presented here demonstrate that there is a link between IBMPFD and NF1 and indicate a role for VCP in synapse formation...
  40. pmc Another VCP interactor: NF is enough
    Conrad C Weihl
    Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
    J Clin Invest 121:4627-30. 2011
    ..Thus, aberrant interactions between VCP and NF1 may explain the dementia phenotype and cognitive delay observed in patients with IBMPFD and neurofibromatosis type 1...
  41. ncbi Neurofibroma-associated growth factors activate a distinct signaling network to alter the function of neurofibromin-deficient endothelial cells
    Amy M Munchhof
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W Walnut Street, Indianapolis, IN 46202, USA
    Hum Mol Genet 15:1858-69. 2006
    ..Thus, these studies identify a unique biochemical pathway in Nf1+/- ECs as a potential therapeutic target in the neurofibroma microenvironment...
  42. pmc Neurofibromatosis-1 heterozygosity impairs CNS neuronal morphology in a cAMP/PKA/ROCK-dependent manner
    Jacquelyn A Brown
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Cell Neurosci 49:13-22. 2012
    ....
  43. ncbi Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1
    L E Side
    Department of Pediatrics, University of California, San Francisco, CA, USA
    Blood 92:267-72. 1998
    ..Because 10% to 14% of children with JMML have a clinical diagnosis of NF1, these data are consistent with the existence of NF1 mutations in approximately 30% of JMML cases...
  44. pmc Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions
    Feng Chun Yang
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Clin Invest 116:2880-91. 2006
    ..Collectively, our results identify a what we believe to be a novel cellular and biochemical NF1-haploinsufficient phenotype in osteoclasts that has potential implications for the pathogenesis of NF1 bone disease...
  45. ncbi Neurofibromin: a general outlook
    A B Trovó-Marqui
    Departamento de Biologia, UNESP Universidade Estadual Paulista, Brazil
    Clin Genet 70:1-13. 2006
    ..2, and has different biochemical functions, including association to microtubules and participation in several signaling pathways. Alterations in this protein are responsible for a phacomatosis named neurofibromatosis type 1...
  46. pmc Nf1 has an essential role in endothelial cells
    Aaron D Gitler
    Department of Medicine, Cardiology Division, University of Pennsylvania Health System, 954 BRB II III, 421 Curie Blvd, Philadelphia, Pennsylvania 19104, USA
    Nat Genet 33:75-9. 2003
    ..These results establish a new and essential role for Nf1 in endothelial cells and confirm the requirement for neurofibromin in the neural crest...
  47. ncbi Somatic mutations in the neurofibromatosis 1 gene in human tumors
    Y Li
    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84112
    Cell 69:275-81. 1992
    ..Thus, germline mutations in NF1 that cause neurofibromatosis 1 can also occur in somatic cells and contribute to the development of sporadic tumors, including tumors not associated with neurofibromatosis 1...
  48. pmc The neurofibromatosis type I pre-mRNA is a novel target of CELF protein-mediated splicing regulation
    Victoria A Barron
    Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    Nucleic Acids Res 38:253-64. 2010
    ..These studies, combined with our previous investigations demonstrating a role for Hu proteins and TIA-1/TIAR in controlling NF1 exon 23a inclusion, highlight the complex nature of regulation of this important alternative splicing event...
  49. ncbi Neurofibromatosis
    Andrea I McClatchey
    Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Annu Rev Pathol 2:191-216. 2007
    ..An important outcome of the study of neurofibromatosis-associated tumorigenesis has been insight into the more general molecular and cellular bases of nervous system tumors...
  50. pmc Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner
    Sutapa Banerjee
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 108:15996-6001. 2011
    ..Collectively, these findings establish TSC/Rheb-independent mechanisms for mTOR-dependent glial cell growth control and gliomagenesis relevant to the design of therapies for individuals with glioma...
  51. ncbi Induction of abnormal proliferation by nonmyelinating schwann cells triggers neurofibroma formation
    Huarui Zheng
    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Cancer Cell 13:117-28. 2008
    ..Subsequent degeneration of abnormal Remak bundles was accompanied by initial expansion of nonmyelinating Schwann cells. We suggest abnormally differentiated Remak bundles as a cell of origin for plexiform neurofibroma...
  52. ncbi RAS pathway activation and an oncogenic RAS mutation in sporadic pilocytic astrocytoma
    Mukesh K Sharma
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neurology 65:1335-6. 2005
  53. ncbi Genetic and cellular defects contributing to benign tumor formation in neurofibromatosis type 1
    J L Rutkowski
    Departments of Neurology and Pediatrics, University of Pennsylvania, Philadelphia, PA 19104 4318, USA
    Hum Mol Genet 9:1059-66. 2000
    ..Our findings further indicate that additional molecular events aside from NF1 inactivation in Schwann cells and/or other neural crest derivatives contribute to neurofibroma formation...
  54. ncbi The tumor suppressor neurofibromin confers sensitivity to apoptosis by Ras-dependent and Ras-independent pathways
    S Shapira
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel
    Cell Death Differ 14:895-906. 2007
    ..Therefore, besides its Ras-dependent growth inhibition, neurofibromin can exert tumor suppression via a proapoptotic effect...
  55. ncbi Bipartite interaction between neurofibromatosis type I protein (neurofibromin) and syndecan transmembrane heparan sulfate proteoglycans
    Y P Hsueh
    Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, 115, Republic of China
    J Neurosci 21:3764-70. 2001
    ..Our findings suggest that interaction with different members of the syndecan family may be a mechanism for localizing neurofibromin to specialized domains of the plasma membrane...
  56. ncbi cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product
    D A Marchuk
    Department of Human Genetics, University of Michigan Medical Center, Ann Arbor 48109
    Genomics 11:931-40. 1991
    ..The gene extends for approximately 300 kb on chromosome 17, with its promoter in a CpG-rich island...
  57. ncbi Rac1 mediates the osteoclast gains-in-function induced by haploinsufficiency of Nf1
    Jincheng Yan
    Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Hum Mol Genet 17:936-48. 2008
    ..Collectively, these data demonstrate that Rac1 critically contributes to increased osteoclast function induced by haploinsufficiency of Nf1 and implicate Rac1 as a rational therapeutic target for osteoporosis...
  58. ncbi The interferon consensus sequence-binding protein activates transcription of the gene encoding neurofibromin 1
    Chunliu Zhu
    Feinberg School of Medicine and the Robert H Lurie Comprehensive Cancer Center, Northwestern University and Chicago Lakeside Veterans Affairs Hospital, Chicago, Illinois 60611, USA
    J Biol Chem 279:50874-85. 2004
    ..In these studies, we identify the gene encoding neurofibromin 1 (Nf1) as an ICSBP target gene, by chromatin immunoprecipitation...
  59. ncbi Spatiotemporal differences in CXCL12 expression and cyclic AMP underlie the unique pattern of optic glioma growth in neurofibromatosis type 1
    Nicole M Warrington
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cancer Res 67:8588-95. 2007
    ..Collectively, these studies provide a mechanism for the unique pattern of NF1-associated glioma growth...
  60. pmc Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain
    R Fahsold
    Gemeinschaftspraxis B Prager and A Junge, Dresden, Germany
    Am J Hum Genet 66:790-818. 2000
    ..Coincidence of mutated amino acids and those conserved between human and Drosophila strongly suggest significant functional relevance of this region, with major roles played by exons 12a and 15 and part of exon 16...
  61. ncbi Life extension through neurofibromin mitochondrial regulation and antioxidant therapy for neurofibromatosis-1 in Drosophila melanogaster
    James Jiayuan Tong
    Center for Molecular and Mitochondrial Medicine and Genetics with Department of Biological Chemistry, Ecology and Evolutionary Biology, University of California, Irvine, California 92697, USA
    Nat Genet 39:476-85. 2007
    ..Thus, neurofibromin regulates longevity and stress resistance through cAMP regulation of mitochondrial respiration and ROS production, and NF1 may be treatable using catalytic antioxidants...
  62. pmc Tumor microenvironment and neurofibromatosis type I: connecting the GAPs
    L Q Le
    Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, The University of Texas Southwestern Medical Center, Dallas, TX, USA
    Oncogene 26:4609-16. 2007
    ..Therefore, further understanding of the molecular interactions between Schwann cells and their environment will provide tools to develop new therapies aimed at delaying or preventing tumor formation in Nf1 patients...
  63. pmc MicroRNA-193b enhances tumor progression via down regulation of neurofibromin 1
    Michelle Lenarduzzi
    Ontario Cancer Institute, University Health Network, Toronto, Canada
    PLoS ONE 8:e53765. 2013
    ..algorithms with in vitro experimental mRNA profilings, plus mRNA expression data of clinical specimens, neurofibromin 1 (NF1) was identified to be a target of miR-193b...
  64. ncbi Characterization of the somatic mutational spectrum of the neurofibromatosis type 1 (NF1) gene in neurofibromatosis patients with benign and malignant tumors
    Meena Upadhyaya
    Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK
    Hum Mutat 23:134-46. 2004
    ..These findings are consistent with the view that NF1 tumorigenesis is a complex multistep process involving a variety of different types of genetic defect at multiple loci...
  65. pmc Automated comparative sequence analysis identifies mutations in 89% of NF1 patients and confirms a mutation cluster in exons 11-17 distinct from the GAP related domain
    C Mattocks
    Department of Medical Genetics, Box 134, Addenbrooke s Hospital, Cambridge, UK
    J Med Genet 41:e48. 2004
  66. pmc Recurrent mutations in the NF1 gene are common among neurofibromatosis type 1 patients
    E Ars
    Centre de Genètica Mèdica i Molecular IRO, Hospital Duran i Reynals, Barcelona, Spain
    J Med Genet 40:e82. 2003
  67. ncbi Neurofibromatosis type I tumor suppressor neurofibromin regulates neuronal differentiation via its GTPase-activating protein function toward Ras
    Shunji Yunoue
    Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Kumamoto 860 0811, Japan
    J Biol Chem 278:26958-69. 2003
    ..These results demonstrate that the mutual regulation of Ras and NF1-GAP is essential for normal neuronal differentiation and that abnormal regulation in neuronal cells may be implicated in NF1-related learning and memory disturbance...
  68. ncbi Neurofibromin GTPase-activating protein-related domains restore normal growth in Nf1-/- cells
    K K Hiatt
    Herman B Wells Center for Pediatric Research, Departments of Microbiology/Immunology and Pediatrics, Indiana University School of Medicine, Indianapolis 46202, USA
    J Biol Chem 276:7240-5. 2001
    ..Thus, the GRDs of neurofibromin and p120GAP specify nonoverlapping functions in multiple primary cell types...
  69. pmc Sensitivity of glioblastomas to clinically available MEK inhibitors is defined by neurofibromin 1 deficiency
    Wendy L See
    Department of Neurological Surgery, University of California, San Francisco, California 94158, USA
    Cancer Res 72:3350-9. 2012
    Loss of neurofibromin 1 (NF1) leads to hyperactivation of RAS, which in turn signals through the RAF/MEK/ERK and phosphoinositide 3-kinase (PI3K)/mTOR pathways to regulate cell growth and survival...
  70. ncbi A molecular analysis of individuals with neurofibromatosis type 1 (NF1) and optic pathway gliomas (OPGs), and an assessment of genotype-phenotype correlations
    Saba Sharif
    Department of Clinical Genetics, West Midlands Regional Genetics Unit, Birmingham, UK
    J Med Genet 48:256-60. 2011
    ..A genotype-phenotype correlation may help to determine who is at risk of developing these tumours, aid focused screening, and shed light on response to treatments...
  71. pmc ERK inhibition rescues defects in fate specification of Nf1-deficient neural progenitors and brain abnormalities
    Yuan Wang
    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Cell 150:816-30. 2012
    ..This study reveals a critical role for Nf1 in maintaining postnatal SVZ-derived neurogenesis and identifies a potential therapeutic window for treating NF1-associated brain abnormalities...
  72. pmc Neurofibromatosis-1 regulates neuroglial progenitor proliferation and glial differentiation in a brain region-specific manner
    Da Yong Lee
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genes Dev 24:2317-29. 2010
    ....
  73. pmc Reduced striatal dopamine underlies the attention system dysfunction in neurofibromatosis-1 mutant mice
    Jacquelyn A Brown
    Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
    Hum Mol Genet 19:4515-28. 2010
    ..Collectively, these data establish abnormal DA homeostasis as the primary biochemical defect underlying the attention system dysfunction in Nf1 GEM relevant to children with NF1...
  74. pmc Alterations in white matter microstructure in neurofibromatosis-1
    Katherine H Karlsgodt
    Semel Institute for Neuroscience and Behavior, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 7:e47854. 2012
    ..Further, this indicates that axial and radial diffusivity can uniquely contribute as markers of NF1-associated brain pathology in conjunction with the typically investigated measures...
  75. pmc Schweinfurthin A selectively inhibits proliferation and Rho signaling in glioma and neurofibromatosis type 1 tumor cells in a NF1-GRD-dependent manner
    Thomas J Turbyville
    National Cancer Institute Frederick, Frederick, Maryland, USA
    Mol Cancer Ther 9:1234-43. 2010
    ....
  76. ncbi Molecular evolution of a neurofibroma to malignant peripheral nerve sheath tumor (MPNST) in an NF1 patient: correlation between histopathological, clinical and molecular findings
    Gill Spurlock
    Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN Wales, UK
    J Cancer Res Clin Oncol 136:1869-80. 2010
    ..This study analyzed the genetic alterations associated with this pathological heterogeneity in order to identify the genetic processes involved in transformation from a benign to an aggressive malignant tumor...
  77. pmc Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice
    Kelly A Diggs-Andrews
    Departments of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 73:309-15. 2013
    ....
  78. pmc Nf1-dependent tumors require a microenvironment containing Nf1+/-- and c-kit-dependent bone marrow
    Feng Chun Yang
    Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Cell 135:437-48. 2008
    ..Further, genetic or pharmacologic attenuation of c-kit signaling in Nf1+/- hematopoietic cells diminishes neurofibroma initiation and progression. Finally, these studies implicate mast cells as critical mediators of tumor initiation...
  79. ncbi The role of steroid hormones in the NF1 phenotype: focus on pregnancy
    Therese M Roth
    Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109 2200, USA
    Am J Med Genet A 146:1624-33. 2008
    ..However, in this review, we consider evidence from the literature that both direct hormonal influence on tumor growth and on angiogenesis may contribute to these effects...
  80. ncbi Neurofibromin, a tumor suppressor in the nervous system
    Y Zhu
    Center for Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390 9133, USA
    Exp Cell Res 264:19-28. 2001
  81. ncbi Glioma formation in neurofibromatosis 1 reflects preferential activation of K-RAS in astrocytes
    Biplab Dasgupta
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cancer Res 65:236-45. 2005
    ....
  82. ncbi Pigment cell-related manifestations in neurofibromatosis type 1: an overview
    Sofie De Schepper
    Department of Dermatology, Ghent University, De Pintelaan 185, B 9000 Ghent, Belgium
    Pigment Cell Res 18:13-24. 2005
    ..Finally, we want to address the relationship between malignant melanoma and NF1...
  83. ncbi The Ras inhibitor farnesylthiosalicylic acid as a potential therapy for neurofibromatosis type 1
    Batya Barkan
    Department of Neurobiochemistry, The George S Wise Faculty of Life Sciences and Sackler School of Medicine, Tel Aviv University, Tel Aviv, and The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Sheba Medical, Tel Hashomer, Israel
    Clin Cancer Res 12:5533-42. 2006
    ..We assessed the ability of FTS to reverse the transformed phenotype of neurofibromatosis type 1 (NF1)-associated tumor cell lines of malignant peripheral nerve sheath tumor (MPNST)...
  84. ncbi Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors
    Biplab Dasgupta
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
    Cancer Res 65:2755-60. 2005
    ..These results suggest that mTOR pathway inhibition may represent a logical and tractable biologically based therapy for brain tumors in NF1...
  85. ncbi Rescue of a Drosophila NF1 mutant phenotype by protein kinase A
    I The
    Massachusetts General Hospital Cancer Center and Harvard Medical School Building 149, 13th Street, Charlestown, MA 02129, USA
    Science 276:791-4. 1997
    ..Thus, NF1 and PKA appear to interact in a pathway that controls the overall growth of Drosophila...
  86. pmc Role of TC21/R-Ras2 in enhanced migration of neurofibromin-deficient Schwann cells
    Yuan Huang
    Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati, College of Medicine, 3125 Eden Ave, Cincinnati, OH 45267 0521, USA
    Oncogene 23:368-78. 2004
    ..These data reveal a key role for neurofibromin regulation of TC21/R-Ras2 in Schwann cells, a cell type critical to NF1 tumor pathogenesis...
  87. pmc An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation
    M Upadhyaya
    Institute of Medical Genetics, Cardiff University, Cardiff, CF14 4XN, UK
    Am J Hum Genet 80:140-51. 2007
    ..The biological mechanism that relates this specific mutation to the suppression of cutaneous neurofibroma development is unknown...
  88. pmc Juvenile xanthogranuloma in a child with previously unsuspected neurofibromatosis type 1 and juvenile myelomonocytic leukemia
    Margarita Raygada
    Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Developmental Genetics, Bethesda, MD 20892 1831, USA
    Pediatr Blood Cancer 54:173-5. 2010
    ..The patient underwent bone marrow transplantation and is currently in remission. Children with concurrent cutaneous café-au-lait and JXG lesions should be evaluated and monitored closely for the possible development of JMML...
  89. ncbi Pheochromocytomas in Nf1 knockout mice express a neural progenitor gene expression profile
    J F Powers
    Department of Pathology, Tufts New England Medical Center, 750 Washington Street, Boston, MA 02111, USA
    Neuroscience 147:928-37. 2007
    ....
  90. ncbi Aberrant growth and differentiation of oligodendrocyte progenitors in neurofibromatosis type 1 mutants
    Michael R Bennett
    Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0521, USA
    J Neurosci 23:7207-17. 2003
    ..The data reveal a key role for neurofibromin and Ras signaling in the maintenance of CNS progenitor cell pools and also suggest a potential role for progenitor cell defects in the CNS abnormalities of NF1 patients...
  91. ncbi Differential localization of the neurofibromatosis 1 (NF1) gene product, neurofibromin, with the F-actin or microtubule cytoskeleton during differentiation of telencephalic neurons
    C Li
    Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA
    Brain Res Dev Brain Res 130:231-48. 2001
    ..In summary, we have shown that telencephalic neurons and astroblasts are enriched in neurofibromin and that the subcellular targeting of neurofibromin toward the actin or the microtubule cytoskeleton is developmentally regulated...
  92. ncbi Neurofibromin regulates G protein-stimulated adenylyl cyclase activity
    Jiayuan Tong
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nat Neurosci 5:95-6. 2002
    ....
  93. ncbi Germline and somatic NF1 gene mutations in plexiform neurofibromas
    Meena Upadhyaya
    Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff CF144XN, UK
    Hum Mutat 29:E103-11. 2008
    ..Evidence for LOH involving the TP53 gene identified in the PNFs is also reported for the first time...
  94. ncbi Nf1 haploinsufficiency augments angiogenesis
    M Wu
    Department of Pediatrics, Division of Neurology, University of Florida, Gainesville, FL 32610, USA
    Oncogene 25:2297-303. 2006
    ..These findings support the conclusion that Nf1 heterozygosity in endothelial cells and perhaps inflammatory cells augments angiogenesis, which may promote neurofibroma formation in NF1...
  95. ncbi Neurocognitive dysfunction in children with neurofibromatosis type 1
    Tena L Rosser
    Department of Neurology, Children s National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA
    Curr Neurol Neurosci Rep 3:129-36. 2003
    ..The development of NF1 animal models with learning and memory difficulties similar to those seen in humans demonstrates promising preliminary evidence that medical treatment of cognitive abnormalities may one day be possible...
  96. ncbi NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype
    Eric Pasmant
    UMR745 INSERM, Universite Paris Descartes, Faculte des Sciences Pharmaceutiques et Biologiques, 4 av de l Observatoire, 75006, Paris, France
    Hum Mutat 31:E1506-18. 2010
    ..High-resolution array-CGH identified a new recurrent approximately 1.0 Mb microdeletion type, designated as type-3, with breakpoints in the paralogous regions middle NF1-REP-b and distal NF1-REP-c...
  97. pmc Epidermal growth factor receptor expression in neurofibromatosis type 1-related tumors and NF1 animal models
    J E DeClue
    Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892, USA
    J Clin Invest 105:1233-41. 2000
    ..Consistent with this hypothesis, growth of NF1 MPNST lines and the transformed NF1(-/-) mouse embryo Schwann cells was greatly stimulated by EGF in vitro and could be blocked by agents that antagonize EGF-R function...
  98. ncbi Developmental regulation of a neuron-specific neurofibromatosis 1 isoform
    D H Gutmann
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 46:777-82. 1999
    ....
  99. ncbi Genomic organization of the neurofibromatosis 1 gene (NF1)
    Y Li
    Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City 84112, USA
    Genomics 25:9-18. 1995
    ..This information should be useful for implementing a comprehensive NF1 mutation screen using genomic DNA as template...
  100. ncbi Nf1 expression is dependent on strain background: implications for tumor suppressor haploinsufficiency studies
    Jessica J Hawes
    Mouse Cancer Genetics Program, National Cancer Institute Frederick, West 7th Street at Fort Detrick, P O Box B, Building 560, Rm 31 20, Frederick, MD 21702, USA
    Neurogenetics 8:121-30. 2007
    ....
  101. ncbi Lymphoproliferative defects in mice lacking the expression of neurofibromin: functional and biochemical consequences of Nf1 deficiency in T-cell development and function
    David A Ingram
    Section of Neonatal Perinatal Medicine, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN 46202, USA
    Blood 100:3656-62. 2002
    ..Collectively, these results identify neurofibromin as a GAP for Ras in T cells for maintaining immune homeostasis in vivo...

Research Grants62

  1. ICSBP Function During Myeloid Differentiation
    ELIZABETH ANN EKLUND; Fiscal Year: 2011
    ..microarray screening, we identified ICSBP- target-genes which encode proteins involved in proliferation (Neurofibromin 1) and apoptosis (Nore1, Fap1 and a soluble guanylate cyclase component)...
  2. Study of Anti-Survival signals in NF1
    CHANGYAN CHEN; Fiscal Year: 2013
    ....
  3. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID W CLAPP; Fiscal Year: 2012
    ..If the hypothesis is correct, we would predict that developing small molecules that inhibit Pak1 function could be useful as a molecular therapy for treatment of plexiform neurofibromas. ..
  4. NEUROFIBROMIN, NEURAL CREST AND CARDIAC DEVELOPMENT
    Jonathan A Epstein; Fiscal Year: 2012
    ....
  5. Role of SAG/RBX2 E3 Ubiquitin Ligase in Skin Carcinogenesis
    Yi Sun; Fiscal Year: 2013
    ..teratomas derived from ES cells, and in B16 melanoma tumorigenesis;2) SAG E3 promotes the degradation of a) neurofibromin 1 (NF1) to activate the RAS/MAPK, b) IkB to activate NFkB, c) DEPTOR to activate mTOR, leading to enhanced ..
  6. SAG E3 ubiquitin ligase in angiogenesis & carcinogenesis
    Yi Sun; Fiscal Year: 2010
    ..Targeting SAG in cancer cells, via siRNA silencing or small molecule inhibitors, would, therefore, be a valid antianglogenesis therapy. ..
  7. Preclinical Testing of Targeted Therapies for Neurofibromas
    DAVID W CLAPP; Fiscal Year: 2011
    ..Finally, using a combination of PET and CT imaging, we now have the ability to image the development, growth, and metabolism of plexiform neurofibromas in genetically engineered mice in vivo as a function of time. ..
  8. Modeling Multi-step Leukemogenesis Nf1 and Kras Mutant Mice
    JENNIFER LAUCHLE; Fiscal Year: 2009
    ..The goal of this project is to model the multi-step process by which a normal cell transforms into leukemia. Improved understanding of these cellular changes will inform drug design and improve treatment and outcome for AML. ..
  9. Novel Treatment of NF-1 Associated Malignant Peripheral Nerve Sheath Tumors
    Steven L Carroll; Fiscal Year: 2012
    ..Inappropriate stimulation by growth factors is thought to cooperate with mutations of tumor suppressor genes such as NF1 and p53 to promote MPNST tumorigenesis. ..
  10. Understanding Mechanisms Underlying Drosophila Neurofibromatosis-1 Defects
    Andre Bernards; Fiscal Year: 2011
    ....
  11. RASA1-mediated control of lymphatic vessel growth and function
    Philip D King; Fiscal Year: 2012
    ..Studies are also of direct relevance to our understanding of the etiology of a vascular disease in humans known as CM- AVM. ..
  12. Axonal Transport and RAS Activation in the NF1 mouse model
    Vinodh Narayanan; Fiscal Year: 2012
    ..Developing similar (safer) imaging methods for human use may provide a method for monitoring treatment efficacy in the clinical setting. ..
  13. Mechanisms for Neurological Dysfunction in NF1 and Noonan Syndrome
    Alcino J Silva; Fiscal Year: 2013
    ..One of these pharmacological inhibitors (lovastatin), currently being tested in NF1 clinical trials, could also eventually be tested in NS clinical trials. ..
  14. Characterizing the role of specific Ras proteins in neurofibroma and MPNST format
    Preeti Tandon; Fiscal Year: 2013
    ..The overall goal of this research is to delineate the functions of Ras proteins in NF1 pathogenesis and to identify novel therapeutic strategies based on inhibition of specific Ras proteins. ..
  15. NF Center: from animal models to therapeutics
    Luis F Parada; Fiscal Year: 2013
    ..Together, the proposed program of research promises to contribute to a better understanding of NF1-associated tumorigenesis at the molecular, cellular, and systems levels. ..
  16. Evaluation of NF1 as a Major Breast Cancer Driver
    John C Schimenti; Fiscal Year: 2013
    ..Strikingly, nearly all Chaos3 mammary tumors underwent deletions of Nf1 (Neurofibromin 1). NF1 is a tumor suppressor that negatively regulates the Ras oncogene...
  17. NEUROFIBROMIN REGULATION OF NEURAL STEM CELL FUNCTION IN VITRO AND IN VIVO
    David H Gutmann; Fiscal Year: 2013
    ..These studies may lead to the development of therapies that specifically target the critical growth and fate control pathways that cause brain tumors in children. ..
  18. New Mechanisms Regulating Ras and Protein Kinase A Signaling
    Yuqi Wang; Fiscal Year: 2013
    ..Specifically, we will test whether silencing Usp10 expression affects Ras signaling in human cells, and whether it does so via deubiquitinating and protecting RasGAP neurofibromin (Ira2 homolog in human) from degradation. ..
  19. Mechanisms of Ras signaling in single synapses
    Ryohei Yasuda; Fiscal Year: 2013
    ..This work will advance our understanding of how Ras couples calcium with synaptic plasticity, and ultimately with learning and memory. ..
  20. Growth Factor-Induced Peripheral Gliogenesis
    Donald Pizzo; Fiscal Year: 2007
    ..Furthermore, the development of a quantitative tumor model allows for the assessment of small molecule therapeutics in a pre-clinical setting. [unreadable] [unreadable]..
  21. PHEOCHROMOCYTOMAS FROM NEUROFIBROMATOSIS KNOCKOUT MICE
    Arthur Tischler; Fiscal Year: 2003
    ..4) To determine the status of neurofibromin in MPC cells and test the hypothesis that abnormal regulation of ras activity is responsible for neuronal differentiation in this model. ..
  22. The role of Pak1 in regulating plexiform neurofibroma formation
    Andrew McDaniel; Fiscal Year: 2009
    ..Preventing or reducing the size of these tumors could increase quality of life for tens of thousands of affected individuals each year. ..
  23. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID CLAPP; Fiscal Year: 2001
    ....
  24. NF1 GENE IN MYELOID LEUKEMIA AND CYTOKINE SIGNALING
    DAVID LARGAESPADA; Fiscal Year: 2002
    ....
  25. MLK3 function in neurofibromatosis tumor cells
    John Kyriakis; Fiscal Year: 2009
    ..Alternatively, merlin could repress the recruitment of MLK3 by Rho family GTPases. In Aim 3, we will use biochemical and molecular biological methods to explore these possibilities. ..
  26. Neurofibromin, Ras & NFAT in Cardiovascular Development
    FRAZ ISMAT; Fiscal Year: 2009
    ..Together this training program will prepare me for independent investigation, lead to a better understanding of cardiovascular abnormalities in neurofibromatosis, and address fundamental issues of cardiovascular development. ..
  27. Elucidating the Function of the NF1 tumor suppressor and its effector pathways in
    KAREN M CICHOWSKI; Fiscal Year: 2013
    ....
  28. NEUROFIBROMIN (Nf1) SIGNALING AND TARGET GENES IN OSTEOBLASTS
    Florent Elefteriou; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  29. ENTEROHEPATIC LIPID FLUX AND APOPROTEIN BIOSYNTHESIS.
    NICHOLAS DAVIDSON; Fiscal Year: 2009
    ..We will examine the hypothesis in the current application that there are other cytidine deaminases, related to apobec-1, with functions involving site-specific RNA interactions. ..
  30. THE ROLE OF NEUROFIBROMIN IN NEURONAL DEVELOPMENT
    Luis Parada; Fiscal Year: 2004
    ....
  31. NF-1 GENE EXPRESSION IN HUMAN SCHWANN CELL FUNCTION
    J Rutkowski; Fiscal Year: 1999
    ....
  32. REGULATION OF NF1 GENE EXPRESSION DURING DIFFERENTIATION
    David Gutmann; Fiscal Year: 1999
    ..An examination of the differential expression and functional properties of these isoforms will provide additional insights into the role of this important tumor suppressor gene in both health and disease. ..
  33. GENETIC AND MOLECULAR STUDIES OF NEUROFIBROMATOSIS 1
    James Gusella; Fiscal Year: 2000
    ....
  34. ANALYSIS OF NEUROFIBROMATOSIS TYPE 1 GENE FUNCTION
    Andre Bernards; Fiscal Year: 2003
    ..These studies will help us understand the normal function of the NF1 gene in vivo and will contribute to our understanding of the diverse manifestations of the disease process. ..
  35. Mechanisms for Neurological Dysfunction in NF1
    Alcino Silva; Fiscal Year: 2007
    ..Importantly, they will also be crucial for developing targeted treatments for the debilitating learning disabilities associated with Neurofibromatosis Type I. ..
  36. DROSOPHILA MODELS FOR STUDYING FUNCTION OF THE NF1 GENE
    Yi Zhong; Fiscal Year: 2003
    ..We expect that the proposed research will lead to new insights into NF1 function and provide new clues for understanding pathogenesis of NF1. ..
  37. Translational Investigation of NF1 in Myeloid Luekemia
    Kevin Shannon; Fiscal Year: 2006
    ..Together, these studies will provide new insights into how Ras signaling is normally regulated in myeloid cells, and how hyperactive Ras contributes to leukemogenesis. ..
  38. Neural stem cells in DRG and neurofibromatosis type 1
    Nancy Joseph; Fiscal Year: 2006
    ..progenitors in the postnatal DRG also raises the question of whether these progenitors are transformed by neurofibromin 1 (NF1) deficiency to form plexiform neurofibromas containing neurons, gila, and myofibroblasts...
  39. Neurofibromin, Ras and BDNF/trkB Signaling
    BRUCE KRUEGER; Fiscal Year: 2005
    ..abstract_text> ..
  40. Cell Signaling and Dendritic Spine Plasticity
    Gang Yi Wu; Fiscal Year: 2009
    ....
  41. Advanced Molecular Diagnostic Test for Neurofibromatosis
    Sadanand Gite; Fiscal Year: 2005
    ..During Phase II, an optimized system for screening NF1 mutations will be developed and clinically evaluated. ..
  42. Neurofibromatosis Foundation International Consortium
    David Gutmann; Fiscal Year: 2003
    ..abstract_text> ..
  43. PROTEIN 4.1 TUMOR SUPPRESSORS IN MENINGIOMA PATHOGENESIS
    David Gutmann; Fiscal Year: 2003
    ..and (3) analyzing the ability of DAL-1 to impair cell growth and motility. These studies are collectively designed to define the role of this novel family of growth regulators in meningioma tumorigenesis and progression. ..
  44. NEUROFIBROMIN AS A NEGATIVE REGULATOR FOR ASTROCYTES
    David Gutmann; Fiscal Year: 2002
    ....
  45. Molecular Determinants of Neural Stem Cell Function
    David Gutmann; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  46. PRECLINICAL MODELS FOR HUMAN ASTROCYTOMAS
    David Gutmann; Fiscal Year: 2004
    ..abstract_text> ..
  47. FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS
    David Gutmann; Fiscal Year: 2003
    ..Our ability to design rational therapies for schwannomas and meningiomas is dependent on an improved understanding of the mechanisms by which loss of merlin expression and function promotes tumor formation. ..
  48. Identification and Preclinical Evaluation of New Brain Tumor Therapies
    David Gutmann; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  49. Actions of GTPase-Activating Proteins on Sensory Neurons
    Cynthia M Hingtgen; Fiscal Year: 2010
    ..Finally, we will begin to examine whether the actions of GAPs on sensory neuron function are mediated through increased activity of the MAPK or PI-3K pathways. ..
  50. Spinal abnormalities in neurofibomatosis type 1
    David H Viskochil; Fiscal Year: 2010
    ..This proposal will identify variables in patients with NF1 as prognostic factors for dystrophic scoliosis to improve clinical management. ..
  51. CHARACTERIZING MICROFIBRIL ABNORMALITIES IN SCLERODERMA
    Dianna Milewicz; Fiscal Year: 2003
    ..The research proposed in this grant will determine the contribution of abnormalities in fibrillin-1-containing microfibrils to the activation of fibroblasts, which leads to the fibrosis that characterizes SSc. ..
  52. Large-scale analysis of human genetic variation via Multiplex Barcode Sequencing
    Michael Dorschner; Fiscal Year: 2007
    ..Additionally, it will be applicable to both genomic DNA templates, and to cDNA enabling simultaneous sampling of genetic variation and gene expression. [unreadable] [unreadable] [unreadable]..
  53. Genetic Basis of Aortic Aneurysms/Dissections
    Dianna Milewicz; Fiscal Year: 2009
    ..Therefore, identification of the genes that predispose individuals to TAAD is critical in preventing premature deaths due to dissections. ..
  54. American Society for Neurochemistry: Annual Conference Grant
    George DeVries; Fiscal Year: 2005
    ..abstract_text> ..
  55. Axonal Oligodendrocyte Signaling in Multiple Sclerosis
    George DeVries; Fiscal Year: 2006
    ..e. migration, proliferation, and survival of OPC cells), which eventually will enable researchers to pinpoint areas for therapeutic intervention. [unreadable] [unreadable]..
  56. FUNCTION OF MIDKINE IN NEUROFIBROMATOSIS
    Andreas Kurtz; Fiscal Year: 2002
    ..In Aim 4 he proposes to study whether MK levels can be detected in skin and/or serum samples of NF1 patients and may serve as a diagnostic indicator for NF1. ..
  57. Regulation of Ras through the Ras GRF exchange factor
    Raymond Mattingly; Fiscal Year: 2005
    ..The results are likely to be of fundamental importance to our comprehension of the role of the Ras/MAP kinase system in learning and memory. ..
  58. NEUROBIOLOGY OF COGNITIVE IMPAIRMENT IN CHILDREN WITH NF
    Bartlett Moore; Fiscal Year: 2003
    ..and medical specialists involved with these patients, "Given that a particular child has or doesn't have brain anomalies, and does or does not have learning difficulties, what will this child be like in the future"? ..
  59. REGULATION OF CD28 SIGNAL TRNSDUCTION
    Philip King; Fiscal Year: 2003
    ..In addition, using a novel yeast-based genetic assay that has been developed in the laboratory, it is proposed to characterize other signaling intermediates that bind the phosphorylated CD28 cytoplasmic tail. ..