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| neurofibromin 2SummarySummary: A membrane protein homologous to the ERM (Ezrin-Radixin-Moesin) family of cytoskeleton-associated proteins which regulate physical properties of membranes. Alterations in neurofibromin 2 are the cause of NEUROFIBROMATOSIS 2. Articles from Journal RESEARCHTop Publications
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Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2
G A Rouleau
Centre de recherche en Neuroscience, McGill University, Montreal, Quebec, Canada
Nature 363:515-21. 1993..Its deduced product has homology with proteins at the plasma membrane and cytoskeleton interface, a previously unknown site of action of tumour suppressor genes in humans...Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus
Wei Li
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Cell 140:477-90. 2010..We propose that Merlin suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4(DCAF1)...Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin
B M McCartney
Department of Zoology, Duke University, Durham, North Carolina 27708 1000, USA
J Cell Biol 133:843-52. 1996..As a result of these studies, we propose that the merlin protein has unique functions in the cell which differ from those of other ERM family members...The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44
H Morrison
Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, and University of Karlsruhe, Institute of Genetics, 76021 Karlsruhe, Germany
Genes Dev 15:968-80. 2001..At low cell density, merlin is phosphorylated, growth permissive, and exists in a complex with ezrin, moesin, and CD44. These data indicate that merlin and CD44 form a molecular switch that specifies cell growth arrest or proliferation...The NF2 tumor suppressor gene product, merlin, inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression
Guang Hui Xiao
Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
Mol Cell Biol 25:2384-94. 2005....The neurofibromatosis 2 protein, merlin, regulates glial cell growth in an ErbB2- and Src-dependent manner
S Sean Houshmandi
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
Mol Cell Biol 29:1472-86. 2009..Lastly, we show that merlin competes with Src for direct binding to ErbB2 and present a novel molecular mechanism for merlin regulation of ErbB2-dependent Src signaling and growth control...Localization to the cortical cytoskeleton is necessary for Nf2/merlin-dependent epidermal growth factor receptor silencing
Banumathi K Cole
Massachusetts General Hospital East, 149 CNY 13th St, Charlestown, MA 02129, USA
Mol Cell Biol 28:1274-84. 2008....Merlin and ERM proteins: unappreciated roles in cancer development?
Andrea I McClatchey
Massachusetts General Hospital Cancer Center, Harvard Medical School Department of Pathology, 149 13th Street, Charlestown, Massachusetts 02129, USA
Nat Rev Cancer 3:877-83. 2003Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors
A I McClatchey
Department of Biology and the Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genes Dev 12:1121-33. 1998..Together, our results suggest an important role for the NF2 tumor suppressor, and perhaps the ERM family in tumor formation and metastasis...Contact-dependent inhibition of EGFR signaling by Nf2/Merlin
Marcello Curto
MGH Center for Cancer Research, Harvard Medical School Department of Pathology, Charlestown, MA 02129, USA
J Cell Biol 177:893-903. 2007..These studies define a new mechanism of tumor suppression, provide mechanistic insight into the poorly understood phenomenon of contact-dependent inhibition of proliferation, and suggest a therapeutic strategy for NF2-mutant tumors...Loss of tumor suppressor Merlin in advanced breast cancer is due to post-translational regulation
K Adam Morrow
Department of Oncologic Sciences, Mitchell Cancer Institute, Mobile, Alabama 36604, USA
J Biol Chem 286:40376-85. 2011....Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas
D Lallemand
INSERM, U674, Paris, France
Oncogene 28:854-65. 2009....The tumor suppressors Merlin and Expanded function cooperatively to modulate receptor endocytosis and signaling
Sushmita Maitra
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637, USA
Curr Biol 16:702-9. 2006..We propose that these proteins control proliferation by regulating the abundance, localization, and turnover of cell-surface receptors and that misregulation of these processes may be a key component of tumorigenesis...Lack of neurofibromatosis type 2 gene promoter methylation in sporadic vestibular schwannomas
D Koutsimpelas
Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, Mainz, Germany
ORL J Otorhinolaryngol Relat Spec 74:33-7. 2012..For a subset of VS without detectable gene alterations, promoter inactivation by hypermethylation has been suggested. However, published data are very limited and contradictory...Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L
Rong Rong
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
Proc Natl Acad Sci U S A 101:18200-5. 2004..Knocking down PIKE-L with RNA interference abolishes merlin's tumor-suppressive activity. Our data support the hypothesis that PIKE-L is an important mediator of merlin growth suppression...Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane
Tomoyo Okada
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
J Cell Biol 171:361-71. 2005..These results provide a framework for understanding the tumor suppressor function of Merlin and indicate that Merlin mediates contact inhibition of growth by suppressing recruitment of Rac to matrix adhesions...The tumor suppressor merlin interacts with microtubules and modulates Schwann cell microtubule cytoskeleton
Taru Muranen
Program of Neuroscience, Department of Pathology, University of Helsinki, Biomedicum Helsinki C511, PL 63, 0014, Finland
Hum Mol Genet 16:1742-51. 2007..The results show that merlin plays a key role in the regulation of the Schwann cell microtubule cytoskeleton and suggest a mechanism by which loss of merlin leads to cytoskeletal defects observed in human schwannomas...Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta
Mark C Wilkes
Thoracic Diseases Research Unit, Department of Biochemistry and Molecular Biology and Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Dev Cell 16:433-44. 2009..These results not only identify Erbin as a key determinant of epithelial resistance to TGF-beta signaling, they also show that Erbin controls Merlin tumor suppressor function by switching the functional valence of PAK2 binding...Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival
Ivan Stamenkovic
Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY10029, USA
Curr Protein Pept Sci 11:471-84. 2010....Loss of the tumor suppressor gene NF2, encoding merlin, constitutively activates integrin-dependent mTORC1 signaling
Miguel A López-Lago
Cell Biology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA
Mol Cell Biol 29:4235-49. 2009....YAP1 is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation
Toshihiko Yokoyama
Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1 1 Kanokoden, Chikusa ku, Nagoya 464 8681, Japan
Carcinogenesis 29:2139-46. 2008..Future studies of transcriptional targets of YAP1 in MPMs may shed light on the molecular mechanisms of MPM development and lead to new therapeutic strategies...The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size
Maria Willecke
Department of Biochemistry and Molecular Biology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Curr Biol 16:2090-100. 2006..However, components acting upstream of Expanded and Merlin, such as transmembrane receptors, have not yet been identified...Merlin and the ERM proteins--regulators of receptor distribution and signaling at the cell cortex
Andrea I McClatchey
Massachusetts General Hospital Center for Cancer Research and Harvard Medical School Department of Pathology, 149 13th Street, Charlestown, MA 02129, USA
Trends Cell Biol 19:198-206. 2009..We also propose a model that could account for the intricacies of Merlin function across model organisms...Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac
Helen Morrison
Institute of Age Research, Fritz Lipmann Institute, Jena, Germany
Cancer Res 67:520-7. 2007..We propose that the interference of merlin with Ras- and Rac-dependent signal transfer represents part of the tumor-suppressive action of merlin...NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth
Marianne F James
Center for Human Genetic Research, Massachusetts General Hospital, Richard B Simches Research Building, 185 Cambridge St, Boston, MA 02114, USA
Mol Cell Biol 29:4250-61. 2009....Missense mutations in the NF2 gene result in the quantitative loss of merlin protein and minimally affect protein intrinsic function
Chunzhang Yang
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 108:4980-5. 2011..These findings provide direct insight into protein function and tumorigenesis in NF2 and indicate a unique treatment paradigm for this disorder...Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase
Hongchuan Jin
Leibniz Institute of Age Research Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany
Nature 442:576-9. 2006..MYPT-1-PP1delta and its substrate merlin are part of a previously undescribed tumour suppressor cascade that can be hindered in two ways, by mutation of the NF2 gene and by upregulation of the oncoprotein CPI-17...Merlin is a potent inhibitor of glioma growth
Ying Ka Ingar Lau
Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
Cancer Res 68:5733-42. 2008..Collectively, our results show that merlin is a potent inhibitor of high-grade human glioma...Merlin isoform 2 in neurofibromatosis type 2-associated polyneuropathy
Alexander Schulz
Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany
Nat Neurosci 16:426-33. 2013..Sciatic nerves from these mice and sural nerve biopsies from NF2 patients revealed reduced phosphorylation of the neurofilament H subunit, decreased interfilament spacings and irregularly shaped axons...Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells
Katherine Kaempchen
Department of Neurology, Zentrum für Klinische Forschung, University of Ulm, Helmholtzstr 8 1, 89081 Ulm, Germany
Hum Mol Genet 12:1211-21. 2003..We conclude that merlin regulates Rac activation, and suggest that this is important for human schwannoma cell dedifferentiation...A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions
Chunling Yi
Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA
Cancer Cell 19:527-40. 2011..Depletion of Angiomotin in Nf2(-/-) Schwann cells attenuates the Ras-MAPK signaling pathway, impedes cellular proliferation in vitro and tumorigenesis in vivo...Merlin inhibits neurite outgrowth in the CNS
Alexander Schulz
Institute of Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, Jena, Germany
J Neurosci 30:10177-86. 2010..We thus provide evidence that merlin plays a pivotal role in controlling the neuronal wiring in the developing CNS...Merlin/NF2 functions upstream of the nuclear E3 ubiquitin ligase CRL4DCAF1 to suppress oncogenic gene expression
Jonathan Cooper
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Sci Signal 4:pt6. 2011..We propose that Merlin mediates contact inhibition and suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4(DCAF1)...Universal absence of merlin, but not other ERM family members, in schwannomas
A O Stemmer-Rachamimov
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, USA
Am J Pathol 151:1649-54. 1997..These data indicate that the specific loss of merlin is universal to schwannomas and is not linked to loss of ezrin, radixin, or moesin expression...The role of insulin-like growth factors signaling in merlin-deficient human schwannomas
Sylwia Ammoun
Clinical Neurobiology, Peninsula Medical School, Plymouth University, Plymouth PL68BU, United Kingdom
Glia 60:1721-33. 2012..PI3K is relevant for both IGF-IR and previously described PDGFR-β signaling in schwannoma...Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin
M Grönholm
Departments of Pathology and Virology, University of Helsinki, Haartman Institute, PO Box 21 Haartmaninkatu 3, FIN 00014 Helsinki
J Cell Sci 112:895-904. 1999..These results biochemically connect merlin to the cortical cytoskeleton and indicate differential regulation of merlin from ERM proteins...Chromosome 22q alterations and expression of the NF2 gene product, merlin, in gastrointestinal stromal tumors
Lea Pylkkanen
Department of Industrial Hygiene, Finnish Institute of Occuapational Health, Helsinki, Finland
Hum Pathol 34:872-9. 2003..The findings suggest that allelic losses at 22q are associated with high mitotic activity and recurring disease, and that alterations in the NF2 gene are unlikely to participate in the pathogenesis of GIST...Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor
S D Yogesha
Cell Adhesion Laboratory, Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida 33458, USA
Protein Sci 20:2113-20. 2011..We conclude the "closed" tumor suppressor conformer of merlin-1 is in fact an "open" dimer whose functions are disabled by Nf2 mutations that disrupt this architecture...Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types
A B Bianchi
Department of Molecular Genetics and Cell Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
Nat Genet 6:185-92. 1994..The NF2 gene may thus constitute a tumour suppressor gene of more general importance in tumorigenesis...Shedding light on Merlin's wizardry
Tomoyo Okada
Cell Biology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Trends Cell Biol 17:222-9. 2007..Here, we review these recent findings and their relevance to the tumor suppressor function of Merlin...NF2-deficient cells depend on the Rac1-canonical Wnt signaling pathway to promote the loss of contact inhibition of proliferation
E E Bosco
Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
Oncogene 29:2540-9. 2010..Thus, Rac1-mediated canonical Wnt signaling is essential for the loss of contact inhibition in NF2-deficient cells...Membrane organization and tumorigenesis--the NF2 tumor suppressor, Merlin
Andrea I McClatchey
Massachusetts General Hospital, Center for Cancer Research and Harvard Medical School, Department of Pathology, Charlestown, Massachusetts 02129, USA
Genes Dev 19:2265-77. 2005..Varying use of this organizing activity by different types of cells could provide an explanation for the unique spectrum of tumors associated with NF2 deficiency in mammals...Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis
K D Hadfield
Academic Unit of Medical Genetics, University of Manchester and Regional Genetics Service, Manchester, UK
J Med Genet 45:332-9. 2008..We aimed to establish the contribution of the SMARCB1 and the NF2 genes to sporadic and familial schwannomatosis in our cohort...Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility, adhesionand spreading
D H Gutmann
The Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
Hum Mol Genet 8:267-75. 1999..These data indicate that merlin may function to maintain normal cytoskeletal organization, and suggest that merlin's influence on cell growth depends on specific cytoskeletal rearrangements...Temporal control of Rac in Schwann cell-axon interaction is disrupted in NF2-mutant schwannoma cells
Yoko Nakai
Division of Experimental Hematology, Cincinnati Children s Hospital Research Foundation, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229, USA
J Neurosci 26:3390-5. 2006..The data support the significance of regulated Rac signaling in mediating Schwann cell-axon interaction and suggest that controlling Rac activity as a possible therapy for schwannomas...Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin
Y Bai
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Oncogene 26:836-50. 2007....Fluorescence resonance energy transfer analysis of merlin conformational changes
Robert F Hennigan
Department of Cancer and Cell Biology, University of Cincinnati, Colege of Medicine, Cincinnati, OH 45267, USA
Mol Cell Biol 30:54-67. 2010..Upon phosphorylation or interaction with an effector protein, merlin undergoes a subtle conformational change, suggesting a novel mechanism that modulates the interaction between the FERM domain and the CTD...Phosphorylation and activity of the tumor suppressor Merlin and the ERM protein Moesin are coordinately regulated by the Slik kinase
Sarah C Hughes
Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
J Cell Biol 175:305-13. 2006..These results suggest the existence of a novel mechanism for coordinate regulation of cell proliferation and epithelial integrity in developing tissues...Erbin regulates mitogen-activated protein (MAP) kinase activation and MAP kinase-dependent interactions between Merlin and adherens junction protein complexes in Schwann cells
Reshma Rangwala
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006, USA
J Biol Chem 280:11790-7. 2005..Collectively, these data indicate that erbin regulates MAP kinase activation in Schwann cells and suggest that erbin links merlin to both adherens junction protein complexes and the MAP kinase signaling pathway...Isolation of mutations in the Drosophila homologues of the human Neurofibromatosis 2 and yeast CDC42 genes using a simple and efficient reverse-genetic method
R G Fehon
Department of Zoology, Duke University, Durham, North Carolina 27708 1000, USA
Genetics 146:245-52. 1997....Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain
M A Pearson
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
Cell 101:259-70. 2000..This extended binding mode suggests a novel mechanism for how different signals could produce varying levels of activation. Sequence conservation suggests a similar regulation of the tumor suppressor merlin...Delineation of a Fat tumor suppressor pathway
Eunjoo Cho
Howard Hughes Medical Institute and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA
Nat Genet 38:1142-50. 2006..melanogaster tumor suppressors, establish a basic framework for Fat signaling from receptor to transcription factor and implicate Warts as an integrator of multiple growth control signals...Akt phosphorylation regulates the tumour-suppressor merlin through ubiquitination and degradation
Xiaoling Tang
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
Nat Cell Biol 9:1199-207. 2007..Furthermore, Akt-mediated phosphorylation leads to merlin degradation by ubiquitination. These studies demonstrate that Akt-mediated merlin phosphorylation regulates the function of merlin in the absence of an inactivating mutation...Functional inactivation of NF2/merlin in human mesothelioma
Claudio Thurneysen
Laboratory of Molecular Oncology, Clinic and Policlinic of Oncology, University Hospital of Zurich, Häldeliweg 4, 8044 Zurich, Switzerland
Lung Cancer 64:140-7. 2009..In tumors where no NF2 truncation can be detected, NF2 is rendered inactive by phosphorylation of Ser 518 and this can be explained at least in part by an increased expression of CPI-17...Tumorigenesis in neurofibromatosis: new insights and potential therapies
N Reed
Department of Neurology, Pediatrics and Genetics, Washington University School of Medicine, Box 8111, 660 S. Euclid Avenue, St Louis, MO 63110, USA
Trends Mol Med 7:157-62. 2001..By understanding the function of these tumor suppressors, we have a unique opportunity to develop targeted pharmacotherapeutic interventions for these disorders...Impaired intercellular adhesion and immature adherens junctions in merlin-deficient human primary schwannoma cells
C Flaiz
Department of Clinical Neurobiology, Institute of Biomedical and Clinical Science, Peninsula College for Medicine and Dentistry, Plymouth, UK
Glia 56:506-15. 2008....Cyclic AMP-dependent protein kinase phosphorylates merlin at serine 518 independently of p21-activated kinase and promotes merlin-ezrin heterodimerization
Kaija Alfthan
Biomedicum Helsinki, Department of Anatomy and Pathology, Neuroscience Program, University of Helsinki and Helsinki University Hospital, FIN 00014 Helsinki, Finland
J Biol Chem 279:18559-66. 2004..This study provides further evidence on the connection between merlin and cAMP/PKA signaling and suggests a role for merlin in the cAMP/PKA transduction pathway...Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology
Cristina Fernandez-Valle
Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida 32826, USA
Nat Genet 31:354-62. 2002..It defines a pathogenic mechanism for the development of NF2 in humans with mutations in exon 2 of NF2...ERM proteins and merlin: integrators at the cell cortex
Anthony Bretscher
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
Nat Rev Mol Cell Biol 3:586-99. 2002..The closely related tumour suppressor merlin shares many properties with ERM proteins, yet also provides a distinct and essential function...A NHERF binding site links the betaPDGFR to the cytoskeleton and regulates cell spreading and migration
Marianne F James
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
J Cell Sci 117:2951-61. 2004..Thus, the interaction of betaPDGFR with NHERF may provide an essential link between the cell membrane and the cortical actin cytoskeleton independent of receptor activity...The NF2 tumor suppressor Merlin and the ERM proteins interact with N-WASP and regulate its actin polymerization function
Nitasha Manchanda
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
J Biol Chem 280:12517-22. 2005..This novel function of merlin and the ERMs illustrates a mechanism by which these proteins directly exert their effects on actin reorganization and also provides new insight into N-WASP regulation...NF2 tumor suppressor gene: a comprehensive and efficient detection of somatic mutations by denaturing HPLC and microarray-CGH
Irene Szijan
Genetica y Biologia Molecular, Facultad de Farmacia y Bioquimica y Hospital de Clinicas, Universitdad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Neuromolecular Med 3:41-52. 2003..Denaturing HPLC analysis of small mutations and microarray-CGH of large deletions are complementary, fast, and efficient methods for the detection of mutations in tumor tissues...Mutational analysis of the NF2 gene in sporadic meningiomas by denaturing high-performance liquid chromatography
Jae Hong Kim
Department of Neurosurgery, School of Medicine, Keimyung University, Daegu 700 712, Korea
Int J Mol Med 18:27-32. 2006..These results provide evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas as well as indicating a different tumorigenesis of these meningioma variants...Tight association of loss of merlin expression with loss of heterozygosity at chromosome 22q in sporadic meningiomas
K Ueki
Department of Neurosurgery, The University of Tokyo Hospital, Japan
Cancer Res 59:5995-8. 1999..These data strongly support the notion that NF2 is the sole target of 22q LOH in meningiomas and that loss of merlin expression is always caused by genetic alteration of NF2, following the classic "two hit" theory...Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin
D R Scoles
Division of Neurology, CSMC Burns and Allen Research Institute, Cedars Sinai Medical Center, University of California School of Medicine at Los Angeles, 90048, USA
Nat Genet 18:354-9. 1998..Thus, schwannomin is a tumour suppressor directly involved in actin-cytoskeleton organization, which suggests that alterations in the cytoskeleton are an early event in the pathogenesis of some tumour types...Neurofibromatosis 2 tumor suppressor protein, merlin, forms two functionally important intramolecular associations
D H Gutmann
Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
J Neurosci Res 58:706-16. 1999..Lastly, we identify NF2 patient mutations that dramatically reduce each of these interactions in vitro. Based on these findings, we propose a model for merlin folding critical to its ability to function as a tumor suppressor protein...Alternative transcripts in the mouse neurofibromatosis type 2 (NF2) gene are conserved and code for schwannomins with distinct C-terminal domains
D P Huynh
Neurogenetics Laboratory, Cedars Sinai Medical Center, UCLA School of Medicine 90048
Hum Mol Genet 3:1075-9. 1994..These results suggest that schwannomin isoforms have distinct functional roles and predict the existence of human mutations involving the C-terminus of schwannomin...Overexpression of Merlin in B16F10 mouse melanoma cells reduces their metastatic activity: role of the cell surface heparan sulfate glycosaminoglycans
Zoya Galcheva-Gargova
Momenta Pharmaceuticals, Inc, Cambridge, MA 02142, USA
Int J Oncol 32:1237-43. 2008..The results obtained provide a causal link between the reorganization/changes to the cell surface HSGAGs by the overexpression of Merlin and the inhibition of the metastatic activity of the mouse melanoma B16F10 cells in vivo...Immunohistochemistry study of human vestibular nerve schwannoma differentiation
Gene Hung
Department of Cell and Molecular Biology, House Ear Institute, Los Angeles, California
Glia 38:363-70. 2002..These results suggest that the NF2 gene might be involved in the differentiation of Schwann cells...Binary regulation of Hippo pathway by Merlin/NF2, Kibra, Lgl, and Melted specifies and maintains postmitotic neuronal fate
David Jukam
Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003 6688, USA
Dev Cell 21:874-87. 2011..These results reveal roles for Merlin, Kibra, and Lgl in neuronal specification and maintenance and show that the Hippo pathway is reimplemented for sensory neuron fate by combining canonical and noncanonical regulatory steps...Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor
T Fukasawa
Department of Pathology, Jichi Medical School, Minami Kawachi Machi, Kawachi, Tochigi 329 0498, Japan
Jpn J Cancer Res 91:1241-9. 2000..NF2 contributes as a tumor suppressor in a small subset of GIST. These abnormalities are presumably followed by increased genetic instability...Altered adhesive structures and their relation to RhoGTPase activation in merlin-deficient Schwannoma
Christine Flaiz
Department of Clinical Neurobiology, Institute of Biomedical and Clinical Science, Peninsula College for Medicine and Dentistry, Plymouth, UK
Brain Pathol 19:27-38. 2009....Structure-function relationships in the ezrin family and the effect of tumor-associated point mutations in neurofibromatosis 2 protein
O Turunen
Department of Virology, Haartman Institute, University of Helsinki, POB 21, FIN 00014 Helsinki, Finland
Biochim Biophys Acta 1387:1-16. 1998..Some known mutations are observed at a site potentially interacting with cell adhesion molecules. We will also discuss the implications of the evolutionary information and the actin-binding models in the ezrin family...A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor
Yumiko Hirokawa
Ludwig Institute for Cancer Research, Melbourne, Australia
Cancer J 10:20-6. 2004..NF2 can inhibit Ras-induced malignant transformation. However, the primary (signaling) target of NF2 in the oncogenic pathway has not been previously identified...The merlin tumor suppressor localizes preferentially in membrane ruffles
C Gonzalez-Agosti
Molecular Neurogenetics Unit, Massachusetts General Hospital East, Charlestown 02129, USA
Oncogene 13:1239-47. 1996..Thus, merlin is associated with motile regions of the cell and its participation in these structures may be intimately involved in control of proliferation in Schwann cells and meningeal cells...Nilotinib alone or in combination with selumetinib is a drug candidate for neurofibromatosis type 2
Sylwia Ammoun
Clinical Neurobiology, Peninsula College for Medicine and Dentistry, The John Bull Building, Tamar Science Park, Research Way, Plymouth PL6 8BU, United Kingdom
Neuro Oncol 13:759-66. 2011..We suggest that therapy with nilotinib or combinational therapy that simultaneously inhibits PDGFR and the downstream Raf/MEK1/2/ERK1/2 pathway could represent an effective treatment for schwannomas and other merlin-deficient tumors...A genetic screen in zebrafish identifies the mutants vps18, nf2 and foie gras as models of liver disease
Kirsten C Sadler
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge MA 02139, USA
Development 132:3561-72. 2005..These mutants illustrate the utility of zebrafish as a model for studying liver development and disease, and provide valuable tools for investigating the molecular pathogenesis of congenital biliary disorders and fatty liver disease...p21-activated kinase links Rac/Cdc42 signaling to merlin
Guang Hui Xiao
Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
J Biol Chem 277:883-6. 2002..These biochemical investigations provide insights into the regulation of merlin function and establish a framework for elucidating tumorigenic mechanisms involved in neoplasms associated with merlin inactivation...The 2.7 A crystal structure of the activated FERM domain of moesin: an analysis of structural changes on activation
S D Edwards
BBSRC Bloomsbury Centre for Structural Biology and School of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK
Biochemistry 40:7061-8. 2001..More interestingly, a negatively charged peptide binds to the inositol site in a crystal contact and causes a greater conformational change in the structure than inositol...NF2 expression levels of gastrointestinal stromal tumors: a quantitative real-time PCR study
Antonio Taddei
Department of Surgical Pathology, University of Florence, School of Medicine, Florence, Italy
Tumori 94:551-5. 2008..NF2 gene mRNA expression was assessed in fresh tissue of stomach from 5 consecutive patients. We detected no alterations in NF2 gene expression in the quantitative analyses of the 5 tumors...The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the "open" conformation and suppresses cell growth and motility
D H Gutmann
Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St Louis, MO 63110, USA
Hum Mol Genet 10:825-34. 2001..These results suggest the possibility that merlin and HRS may regulate cell growth in schwannoma cells through interacting pathways...Magic but treatable? Tumours due to loss of merlin
C O Hanemann
Clinical Neurobiology, Peninsula Medical School, The John Bull Building, Tamar Science Park, Research Way, Plymouth, PL6 8BU, UK
Brain 131:606-15. 2008..Finally, I will discuss how loss of merlin leads to tumourigenesis in order to understand the rationale for emerging new therapeutic targets...Interdomain interaction of merlin isoforms and its influence on intermolecular binding to NHE-RF
C Gonzalez-Agosti
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
J Biol Chem 274:34438-42. 1999....Normal membrane localization and actin association of the NF2 tumor suppressor protein are dependent on folding of its N-terminal domain
E Brault
, U434 INSERM-CEPH Fondation Jean Dausset, 75010 Paris, France
J Cell Sci 114:1901-12. 2001..These results suggest that loss of activity of several naturally occurring schwannomin mutants is due to disruption of the fold of the N-terminal domain, leading to loss of both membrane localization and actin association...NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions
Dominique Lallemand
MGH Cancer Center and Harvard Medical School Department of Pathology, Charlestown, Massachusetts 02129, USA
Genes Dev 17:1090-100. 2003..Our studies indicate that merlin functions as a tumor and metastasis suppressor by controlling cadherin-mediated cell:cell contact...Merlin, the Drosophila homologue of neurofibromatosis-2, is specifically required in posterior follicle cells for axis formation in the oocyte
N MacDougall
Wellcome Centre for Cell Biology, ICMB, King s Buildings, University of Edinburgh, Edinburgh EH9 3JR, UK
Development 128:665-73. 2001..We propose that Merlin acts in response to the Gurken signal by apically targeting the signal that initiates axis specification in the oocyte...Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse
Michel Kalamarides
INSERM U434, Fondation Jean Dausset Centre d Etude du Polymorphisme Humain, 75010 Paris, France
Genes Dev 16:1060-5. 2002..This first mouse model initiated with a genetic lesion found in human meningiomas provides a powerful tool for investigating tumor progression and for the preclinical evaluation of therapeutic interventions...Hierarchy of merlin and ezrin N- and C-terminal domain interactions in homo- and heterotypic associations and their relationship to binding of scaffolding proteins EBP50 and E3KARP
R Nguyen
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
J Biol Chem 276:7621-9. 2001..E3KARP binds tightly to the ezrin N-ERMAD but has little affinity for the merlin N-ERMAD. The implications of these associations and the hierarchies of binding for the function and regulation of merlin and ERM proteins are discussed...The neurofibromatosis-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation
B M McCartney
Developmental, Cell and Molecular Biology Group, Duke University, Durham, NC 27708 1000, USA
Development 127:1315-24. 2000..These results indicate that Merlin and Expanded function together to regulate proliferation and differentiation, and have implications for understanding the functions of other Protein 4.1 superfamily members...Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1
Joseph L Kissil
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Mol Cell 12:841-9. 2003..This link provides a possible mechanism for the effect of loss of merlin expression in tumorigenesis...Effect of merlin phosphorylation on neurofibromatosis 2 (NF2) gene function
Ezequiel I Surace
Department of Neurology, Washington University School of Medicine, Box 8111, 660 S Euclid Avenue, St Louis, MO 63110, USA
Oncogene 23:580-7. 2004....Mixed-lineage kinase 3 regulates B-Raf through maintenance of the B-Raf/Raf-1 complex and inhibition by the NF2 tumor suppressor protein
Deborah N Chadee
Molecular Cardiology Research Institute, Tufts New England Medical Center, Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA
Proc Natl Acad Sci U S A 103:4463-8. 2006..Thus, MLK3 is part of a multiprotein complex and is required for ERK activation. The levels of this complex may be negatively regulated by merlin...Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression
Rong Rong
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
Oncogene 23:8447-54. 2004..These observations suggest that merlin S518 phosphorylation directly modulates merlin intramolecular and intermolecular associations important for the ability of merlin to function as a tumor suppressor...Structural analysis of Drosophila merlin reveals functional domains important for growth control and subcellular localization
D R LaJeunesse
Developmental, Cell and Molecular Biology Group, Department of Zoology, Duke University, Durham, North Carolina 27708 1000, USA
J Cell Biol 141:1589-99. 1998..These results provide insights into the functions and functional organization of a novel tumor suppressor gene...Activation of the tumor suppressor merlin modulates its interaction with lipid rafts
John T Stickney
Department of Cell Biology, Neurobiology, and Anatomy, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Cancer Res 64:2717-24. 2004....Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene
Kseniya Golovnina
Institute of Cytology and Genetics, Russian Academy of Sciences, 630090, Novosibirsk, Russia
BMC Evol Biol 5:69. 2005..While merlin's functional activity has been examined in mammalian and Drosophila models, little is understood about its evolution, diversity, and overall distribution among different taxa...Merlin and the ERM proteins in Schwann cells, neurons and growth cones
Vijaya Ramesh
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Nat Rev Neurosci 5:462-70. 2004Merlin differentially associates with the microtubule and actin cytoskeleton
H M Xu
Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Neurosci Res 51:403-15. 1998..These microtubule association results confirm the notion that merlin exists in "open" and "closed" conformations relevant to its function as a negative growth regulator...NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins
A Murthy
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
J Biol Chem 273:1273-6. 1998....The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association
M F James
Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
Biochem J 356:377-86. 2001..Comparison of these findings with those reported for ERM proteins reveal a distinct role for merlin in actin filament dynamics...The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling
R J Shaw
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
Dev Cell 1:63-72. 2001..Finally, Nf2-/- cells exhibit characteristics of cells expressing activated alleles of Rac. These studies provide insight into the normal cellular function of merlin and how Nf2 mutation contributes to tumor initiation and progression...
Research Grants
- Contribution of c-Jun N-terminal kinase activity to vestibular schwannoma growthMarlan R Hansen; Fiscal Year: 2013..The results of these studies will provide insights into the fundamental mechanisms contributing to VS cell growth and radiosensitivity and will likely contribute to the development of novel therapies for VSs. ..
- Control of cell number in developing retinaDuojia Pan; Fiscal Year: 2013..Such insights may facilitate the therapeutic interventions of relevant human diseases, including diseases of the retina. ..
- Role of CD98 Glycoprotein in Intestinal InflammationHamed Laroui; Fiscal Year: 2013..g. DDW and FASEB), and receive guidance from a selected Career Development Research Advisory Committee. ..
- Identification of Novel Drug Targets For Use in Preventing Deafness Caused by NF2CRISTINA MARIA FERNANDEZ-VALLE; Fiscal Year: 2013..These studies are initial steps in validating LIMK and/or cofilin as drug targets for development of an effective treatment for NF2 aimed at preserving hearing. ..
- Mechanism of Merlin-mediated contact inhibition and tumor suppression.Filippo G Giancotti; Fiscal Year: 2013..It is expected that a mechanistic understanding of Merlin's function will shed light on contact inhibition and on the pathogenesis of NF2 mutant tumors. ..
- The Role of p21-Activated Kinases in Malignant MesotheliomaJoseph R Testa; Fiscal Year: 2013....
- Molecular determinants of breast cancer malignancyLalita A Shevde; Fiscal Year: 2013....
- Merlin regulation of spinal cord NSC functionCynthia Garcia; Fiscal Year: 2013..Collectively, these studies provide unprecedented opportunities to leverage developmental neurobiology to identify new drug targets for the treatment of these CNS cancers. ..
- FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUERichard G Fehon; Fiscal Year: 2013..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development. ..
- Preclinical Treatment for NF2-Associated TumorsVijaya Ramesh; Fiscal Year: 2013..These studies will have impact not only on NF2, but also on sporadic meningiomas and schwannomas, which are quite common in the general population. ..
- Mechanisms of cell contact inhibition and their dysregulation in cancer.JOSEPH KISSIL; Fiscal Year: 2013....
- Molecular Function of the Nf2 Tumor Suppressor, MerlinAndrea I McClatchey; Fiscal Year: 2013..We also plan to determine whether Merlin controls the surface availability of ErbB3 via a similar mechanism. ..
- Exploration of Activity of RAD001 in vivo in Vestibular Schwannomas and MeningiomMATTHIAS ANGELOS KARAJANNIS; Fiscal Year: 2013..The identification of an effective medical therapy for VS and meningiomas would represent a breakthrough in neuro-oncology and enhance the quality of life and survival in patients with these tumors. ..
- Connecting PTEN and NF2 cancer predisposition syndromesMaria Magdalena Georgescu; Fiscal Year: 2009..abstract_text> ..
- Structure, Function and Regulation of MerlinWallace Ip; Fiscal Year: 2009..We anticipate that these studies will shed new light on pathways involved in merlin-mediated tumor suppression, and may suggest possible molecular targets for therapeutic strategies for tumors that arise from loss of merlin function. ..
- Merlin Signal in Glioma: Therapeutic Agents and TargetsQin Yu; Fiscal Year: 2010..Therefore, this proposal has high biological and clinical relevance ..
- Growth Factor-Induced Peripheral GliogenesisDonald 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]..
- A Wheelchair Anti-Rollback DeviceSteve Green; Fiscal Year: 2012..It is light, inexpensive, has high utility, and can be retrofitted easily to most wheelchairs. It also reduces the risk of turnovers while propelling up ramps, and lessens the upper extremity stresses imposed by the manual propulsion. ..
- MLK3 function in neurofibromatosis tumor cellsJohn 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. ..
- MOLECULAR GENETIC ALTERATIONS IN MALIGNANT MESOTHELIOMAJOSEPH TESTA; Fiscal Year: 2006..Overall, these studies are expected to provide insights regarding mechanisms by which specific TSGs contribute to the pathogenesis of MM and delineate potential avenues for therapeutic intervention. ..
- Accurate detection of chromosomal abnormalities with multi-color image processingYu Ping Wang; Fiscal Year: 2009..This will in turn benefit the health of human beings. Furthermore, the developed computational techniques can be applicable to a wide range of multi-color bio-imaging problems, thereby having a broad impact on the biomedical community. ..
- ErbB receptor regulation of Vestibular SchwannomasJONI DOHERTY; Fiscal Year: 2009..Treatment is limited to surgery or radiation. The proposed project investigates the molecular events that cause vestibular schwannomas with the goal of developing a new medical treatment alternative. ..
- A Manual Standup WheelchairSteve Green; Fiscal Year: 2010....
- NF2 BINDING PROTEINSStefan Pulst; Fiscal Year: 2000..Based on nucleolar localization of schwannomin in STS26T Schwann cells, its effect on RNA polymerase I transcription will be assayed in vitro using nuclear extracts, purified transcription factors and recombinant proteins. ..
- Transcriptional regulation of growth downstream of tumor suppressor pathwaysHyangyee Oh; Fiscal Year: 2009....
- The NF2 gene: elucidation of tumor suppressor functionJOSEPH KISSIL; Fiscal Year: 2004..This should lead to a better understanding of merlin function in normal cells and the consequences of its loss in tumor development. Such information will directly assist in the search for effective therapies. ..
- Fine mapping 8q24 in Familial Bipolar DisorderMelvin McInnis; Fiscal Year: 2007..With the identification, replication and characterization of the association for BP and 8q24 we will be in a strong positionto pursue further gene and functional studies. ..
- Variance Component Models for Mapping QTLsJohn Hewitt; Fiscal Year: 2006..abstract_text> ..
- NEUROFIBROMIN AS A NEGATIVE REGULATOR FOR ASTROCYTESDavid Gutmann; Fiscal Year: 2002....
- FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONSDavid 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. ..
- PROTEIN 4.1 TUMOR SUPPRESSORS IN MENINGIOMA PATHOGENESISDavid 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. ..
- Neurofibromatosis Foundation International ConsortiumDavid Gutmann; Fiscal Year: 2003..abstract_text> ..
- Identification and Preclinical Evaluation of New Brain Tumor TherapiesDavid Gutmann; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- PRECLINICAL MODELS FOR HUMAN ASTROCYTOMASDavid Gutmann; Fiscal Year: 2004..abstract_text> ..
- Molecular Determinants of Neural Stem Cell FunctionDavid Gutmann; Fiscal Year: 2008..unreadable] [unreadable] [unreadable] [unreadable]..
- Merlin regulation of glial cell growth and motilitySHERVIN HOUSHMANDI; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Regulation of Mixed Lineage Kinase 3 by the tumor suppressor protein MerlinDEBORAH CHADEE; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Stem Cell Regulation by the NF2 Tumor Suppressor MerlinAndrew Gladden; Fiscal Year: 2008..unreadable] [unreadable] [unreadable] [unreadable]..
- Computational and Statistical Models for Human PedigreesGONCALO ROCHA ABECASIS; Fiscal Year: 2008..abstract_text> ..
- Vitamin D Hormone: Function and Mechanism of ActionSYLVIA S CHRISTAKOS; Fiscal Year: 2010....
- Integrated Parametric and Non-parametric Mapping for Genome-Wife Association DataGONCALO ROCHA ABECASIS; Fiscal Year: 2008..The resulting data, together with genotype data from at least two other genome-wide association scans, will allow us to evaluate and calibrate our methods for association mapping. [unreadable] [unreadable] [unreadable] [unreadable]..
- Gene Mapping of Complex Traits Using Resequencing DataGONCALO ROCHA ABECASIS; Fiscal Year: 2010..Here, we propose to develop efficient methods for analyzing high-throughput sequence data and to distribute software tools that allow others to extract maximum benefit from our methods. ..
- TESTING SLE CANDIDATE LOCI USING CASES AND THEIR PARENTSLindsey Criswell; Fiscal Year: 2003..Finally, the families recruited for this study will serve as a valuable resource for future genetic epidemiology studies of SLE. Therefore, the efforts of this project represent an important investment for the future. ..
- CHARACTERIZATION OF TSC PROTEIN HAMARTIN AND TUBERINVijaya Ramesh; Fiscal Year: 2005..The information obtained here will elucidate the physiological functions of these tumor suppressors, which will aid in designing better therapies. ..
- GENOME-WIDE ANALYSIS FOR ADDICTION SUSCEPTIBILITY GENESHerbert Lachman; Fiscal Year: 2005..By the end of the project, which will coincide with the completion of the human genome project, they will be able to analyze all of the specific candidate genes that map to linked markers. ..
- The Role of Merlin Phosphorylation on its Tumor Suppressive ActivityKeqiang Ye; Fiscal Year: 2010..abstract_text> ..
- Cell Cycle and DevelopmentBRUCE EDGAR; Fiscal Year: 2004....
- Integrating Behavioral and Molecular GeneticsDanielle Dick; Fiscal Year: 2003..My postdoctoral training proposal is illustrative of this interdisciplinary approach, with specific application to the area of alcohol use and abuse. ..
- CONTROL OF SCHWANN CELL DIFFERENTIATIONCristina Fernandez Valle; Fiscal Year: 2002....
- An Association Study of Neurogenin 1 and SchizophreniaAyman Fanous; Fiscal Year: 2002..If there are resources left over, we plan to genotype 400 normal controls and perform a case-control analysis using a chi-squared test to confirm any suggestive findings. ..
- 2006 NF Consortium for NF1, NF2 and SchwannomatosisVijaya Ramesh; Fiscal Year: 2006..This will promote to the research community at large the status of NF research, the link with other cancers and neurological disorders and the key barriers to be addressed. [unreadable] [unreadable] [unreadable]..
- SYK SIGNALING AND BREAST CANCER INVASIONJIALE DAI; Fiscal Year: 2007..2). Taken together, these studies should clarify the mechanisms by which the loss of Syk(L) and aberrant expression of Syk(S) promotes breast cancer progression. [unreadable] [unreadable]..
- Cellular Functions of the Human FilaminsMasumi Eto; Fiscal Year: 2007..abstract_text> ..
- Analysis of Mitochondrial Morphology and FunctionDENNIS LA JEUNESSE; Fiscal Year: 2007..As AREA grant, this project has been designed to accommodate the training and education of undergraduate researchers. [unreadable] [unreadable] [unreadable]..
- Vibrio Cholerae as a bioterror agent: New means of treating a potential pandemicAnjaparavanda Naren; Fiscal Year: 2008..cholerae or due to natural causes. [unreadable] [unreadable] [unreadable]..
- Haplotype analysis of population and pedigree data in association studiesKui Zhang; Fiscal Year: 2007..The meeting will take place in December of 2007 and be attended by scientists from academia, government, and industry. [unreadable] [unreadable] [unreadable]..
- Mechanisms Modulating Cytoskeletal Dynamics During Schwann Cell MyelinationCRISTINA MARIA FERNANDEZ VALLE; Fiscal Year: 2010..abstract_text> ..
- Novel strategies for defining the role of HLA in SLELindsey Criswell; Fiscal Year: 2009..abstract_text> ..
- Phenotypic Determinants of Vestibular SchwannomasD Welling; Fiscal Year: 2009..Successful completion of this study should further elucidate important pathways of vestibular schwannoma formation with good potential for future development of pharmaco-therapeutics. ..
- HERITAGE FAMILY STUDY, PHASE 4Tuomo Rankinen; Fiscal Year: 2010..abstract_text> ..
- Dissecting the HLA contribution to Rheumatoid ArthritisLINDSEY ANN CRISWELL; Fiscal Year: 2010..Finally, due to the clinical and apparent genetic heterogeneity of RA, we will study specific RA phenotypes as secondary outcomes. ..