Richard Hynes

Summary

Affiliation: Massachusetts Institute of Technology
Country: USA

Publications

  1. ncbi The evolution of metazoan extracellular matrix
    Richard O Hynes
    Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 196:671-9. 2012
  2. ncbi Overview of the matrisome--an inventory of extracellular matrix constituents and functions
    Richard O Hynes
    Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cold Spring Harb Perspect Biol 4:a004903. 2012
  3. ncbi Integrins in vascular development
    R O Hynes
    Howard Hughes Medical Institute, Cambridge, MA, USA
    Braz J Med Biol Res 32:501-10. 1999
  4. ncbi A reevaluation of integrins as regulators of angiogenesis
    Richard O Hynes
    Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Med 8:918-21. 2002
  5. ncbi Cell-matrix adhesion in vascular development
    R O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Thromb Haemost 5:32-40. 2007
  6. ncbi Cell adhesion: old and new questions
    R O Hynes
    Howard Hughes Medical Institute and Center for Cancer Research, Dept of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Trends Cell Biol 9:M33-7. 1999
  7. ncbi The emergence of integrins: a personal and historical perspective
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Matrix Biol 23:333-40. 2004
  8. ncbi Metastatic potential: generic predisposition of the primary tumor or rare, metastatic variants-or both?
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 113:821-3. 2003
  9. ncbi Integrins: bidirectional, allosteric signaling machines
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 110:673-87. 2002
  10. ncbi US policies on human embryonic stem cells
    Richard O Hynes
    Howard Hughes Medical Institute, David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 4307, USA
    Nat Rev Mol Cell Biol 9:993-7. 2008

Research Grants

  1. CELL SURFACE STRUCTURE AND TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 2000
  2. CELL SURFACE STRUCTURE AND TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 2005
  3. CELL SURFACE STRUCTURE AND TRANSFORMATION
    Richard Hynes; Fiscal Year: 1980
  4. CELL SURFACE STRUCTURE AND TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 1993
  5. CELL SURFACE STRUCTURE AND CELL TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 1990

Detail Information

Publications94

  1. ncbi The evolution of metazoan extracellular matrix
    Richard O Hynes
    Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 196:671-9. 2012
    ..The recent sequencing of several genomes has revealed many details of this conservation and evolution of ECM proteins to serve diverse functions in metazoa...
  2. ncbi Overview of the matrisome--an inventory of extracellular matrix constituents and functions
    Richard O Hynes
    Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cold Spring Harb Perspect Biol 4:a004903. 2012
    ..This key role of ECM is reflected in the diversity of ECM proteins and the modular domain structures of ECM proteins both allow their multiple interactions and, during evolution, development of novel protein architectures...
  3. ncbi Integrins in vascular development
    R O Hynes
    Howard Hughes Medical Institute, Cambridge, MA, USA
    Braz J Med Biol Res 32:501-10. 1999
    ..Consideration of the results suggests working hypotheses and raises questions for future research directions...
  4. ncbi A reevaluation of integrins as regulators of angiogenesis
    Richard O Hynes
    Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Med 8:918-21. 2002
    ..This apparent paradox suggests the hypotheses that these integrins are negative regulators of angiogenesis and that the drugs targeting them may be acting as agonists rather than antagonists...
  5. ncbi Cell-matrix adhesion in vascular development
    R O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Thromb Haemost 5:32-40. 2007
    ....
  6. ncbi Cell adhesion: old and new questions
    R O Hynes
    Howard Hughes Medical Institute and Center for Cancer Research, Dept of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Trends Cell Biol 9:M33-7. 1999
    ....
  7. ncbi The emergence of integrins: a personal and historical perspective
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Matrix Biol 23:333-40. 2004
  8. ncbi Metastatic potential: generic predisposition of the primary tumor or rare, metastatic variants-or both?
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 113:821-3. 2003
    ..A paper in this month's Cancer Cell and other arguments instead suggest models combining features of both...
  9. ncbi Integrins: bidirectional, allosteric signaling machines
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 110:673-87. 2002
    ..Long-range conformational changes couple these functions via allosteric equilibria...
  10. ncbi US policies on human embryonic stem cells
    Richard O Hynes
    Howard Hughes Medical Institute, David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 4307, USA
    Nat Rev Mol Cell Biol 9:993-7. 2008
    ..These guidelines are functioning well, have influenced developing state regulations and, one hopes, will affect any future federal regulation...
  11. ncbi The extracellular matrix: not just pretty fibrils
    Richard O Hynes
    Howard Hughes Medical Institute, David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 326:1216-9. 2009
    ..As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM...
  12. ncbi Structural biology. Changing partners
    Richard O Hynes
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 300:755-6. 2003
  13. ncbi Fibronectin receptor functions in embryonic cells deficient in alpha 5 beta 1 integrin can be replaced by alpha V integrins
    J T Yang
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts, USA
    Mol Biol Cell 7:1737-48. 1996
    ..Finally, our data suggested possible roles for alpha V integrins in replacing the role of alpha 5 beta 1 in FN matrix assembly in vitro and in FN-dependent embryonic functions in vivo...
  14. ncbi alpha3beta1 Integrin is required for normal development of the epidermal basement membrane
    C M DiPersio
    Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    J Cell Biol 137:729-42. 1997
    ..Our findings support a novel role for alpha3beta1 in establishment and/or maintenance of basement membrane integrity, while alpha6beta4 is required for stable adhesion of the epidermis to the basement membrane through hemidesmosomes...
  15. ncbi Mouse keratinocytes immortalized with large T antigen acquire alpha3beta1 integrin-dependent secretion of MMP-9/gelatinase B
    C M DiPersio
    Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Cell Sci 113:2909-21. 2000
    ....
  16. ncbi The diverse roles of integrins and their ligands in angiogenesis
    R O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cold Spring Harb Symp Quant Biol 67:143-53. 2002
  17. ncbi alpha3beta1 and alpha6beta4 integrin receptors for laminin-5 are not essential for epidermal morphogenesis and homeostasis during skin development
    C M DiPersio
    Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Cell Sci 113:3051-62. 2000
    ..These findings show that while alpha3beta1 and alpha6beta4 are both required for integrity of the dermo-epidermal junction, neither one is essential for epidermal morphogenesis during skin development...
  18. ncbi Embryonic mesodermal defects in alpha 5 integrin-deficient mice
    J T Yang
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
    Development 119:1093-105. 1993
    ..All these functions have previously been thought to involve or require alpha 5 beta 1. The results presented show that these cellular functions involving fibronectin can proceed using other receptors...
  19. ncbi Overlapping and independent functions of fibronectin receptor integrins in early mesodermal development
    J T Yang
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Dev Biol 215:264-77. 1999
    ....
  20. ncbi Reduced blood vessel formation and tumor growth in alpha5-integrin-negative teratocarcinomas and embryoid bodies
    D Taverna
    Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cancer Res 61:5255-61. 2001
    ..Reduced vascularization likely contributed to the reduced proliferation and increased apoptosis observed in alpha5-null teratocarcinomas...
  21. ncbi A test of the role of alpha5 integrin/fibronectin interactions in tumorigenesis
    D Taverna
    Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Cancer Res 58:848-53. 1998
    ..We conclude that, in the genetic backgrounds studied here, loss of fibronectin or alpha5beta1 integrin does not contribute to tumorigenesis or metastasis...
  22. ncbi In vivo roles of integrins during leukocyte development and traffic: insights from the analysis of mice chimeric for alpha 5, alpha v, and alpha 4 integrins
    A G Arroyo
    Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Immunol 165:4667-75. 2000
    ..These results show that integrins play distinct roles during in vivo leukocyte development and traffic...
  23. ncbi Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins
    P Andre
    Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, MA, USA
    Blood 96:3322-8. 2000
    ..It is proposed that this process may rapidly recruit platelets to sites of injury or inflammation in veins...
  24. ncbi Expression of DFak56, a Drosophila homolog of vertebrate focal adhesion kinase, supports a role in cell migration in vivo
    G L Fox
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 96:14978-83. 1999
    ..Consistent with a role in cell migration, we also observe that DFak56 is abundant in the border cells of developing egg chambers before the onset of, and during, their migration...
  25. ncbi Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival
    K M Hodivala-Dilke
    Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Clin Invest 103:229-38. 1999
    ....
  26. ncbi Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins
    B L Bader
    Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, Massachusetts 02139, USA
    Cell 95:507-19. 1998
    ..These results necessitate reevaluation of the primacy of alphav integrins in many functions including vascular development, despite reports that blockade of these integrins with antibodies or peptides prevents angiogenesis...
  27. ncbi Alternative splicing of chicken fibronectin in embryos and in normal and transformed cells
    P A Norton
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139
    Mol Cell Biol 7:4297-307. 1987
    ....
  28. ncbi Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development
    J T Yang
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
    Development 121:549-60. 1995
    ..These results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to block alpha 4 integrin functions in inflammation...
  29. ncbi Drosophila integrins and their ligands
    P J Gotwals
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
    Curr Opin Cell Biol 6:734-9. 1994
    ....
  30. ncbi Drosophila PS1 integrin is a laminin receptor and differs in ligand specificity from PS2
    P J Gotwals
    Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, MA
    Proc Natl Acad Sci U S A 91:11447-51. 1994
    ....
  31. ncbi Functional comparison of the alpha3A and alpha3B cytoplasmic domain variants of the chicken alpha3 integrin subunit
    C M DiPersio
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Exp Cell Res 268:45-60. 2001
    ..Our findings suggest that the alpha3B cytoplasmic domain harbors a retention signal that is regulated in an intact integrin and can alter cell surface expression and distribution of alpha3beta1...
  32. ncbi Differential requirements for alpha4 integrins during fetal and adult hematopoiesis
    A G Arroyo
    Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA
    Cell 85:997-1008. 1996
    ..We also show that alpha4 integrins are essential for T cell homing to Peyer's patches, but not to other secondary lymphoid organs, including spleen, lymph nodes, and intestinal epithelium...
  33. ncbi Mesodermal development in mouse embryos mutant for fibronectin
    E N Georges-Labouesse
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
    Dev Dyn 207:145-56. 1996
    ..These results show that specification of notochordal and somitic mesodermal lineages and significant cell migration are independent of fibronectin but that correct morphogenesis of these structures is FN-dependent...
  34. ncbi Developmental defects in mouse embryos lacking N-cadherin
    G L Radice
    Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Dev Biol 181:64-78. 1997
    ..These results show that N-cadherin plays a critical role in early heart development as well as in other morphogenetic processes...
  35. ncbi Precocious mammary gland development in P-cadherin-deficient mice
    G L Radice
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Cell Biol 139:1025-32. 1997
    ..Furthermore, the loss of P-cadherin from the myoepithelium has uncovered a novel function for this tissue in maintaining the undifferentiated state of the underlying secretory epithelium...
  36. ncbi Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin
    E L George
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
    Development 119:1079-91. 1993
    ..The nature of these embryonic defects leads to reevaluation of suggested roles for fibronectin during early development based on results obtained in vitro and in embryos of other species...
  37. ncbi Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles
    M L Borowsky
    Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Cell Biol 143:429-42. 1998
    ..We have identified a short region within talin's amino-terminal 435 amino acids capable of binding to layilin in vitro. This region overlaps a binding site for focal adhesion kinase...
  38. ncbi Layilin, a novel integral membrane protein, is a hyaluronan receptor
    P Bono
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
    Mol Biol Cell 12:891-900. 2001
    ..This parallelism suggests a role for layilin in cell adhesion and motility...
  39. ncbi Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment
    E Alcamo
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Immunol 167:1592-600. 2001
    ..These results suggest that TNFR1-independent activation of RelA is essential in cells of nonhemopoietic origin during the initiation of an innate immune response...
  40. ncbi Beta 3 integrins regulate lymphocyte migration and cytokine responses in heart transplant rejection
    A Lacy-Hulbert
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
    Am J Transplant 7:1080-90. 2007
    ..Hence we provide strong mechanistic evidence supporting previous genetic studies, demonstrate the involvement of beta 3 integrins in both acute and chronic rejection and identify beta 3 as a new target for immunosuppressive therapy...
  41. ncbi Integrin receptors are required for cell survival and proliferation during development of the peripheral glial lineage
    H Haack
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Dev Biol 233:38-55. 2001
    ..We conclude that integrins can complement growth factors in the control of glial cell numbers...
  42. ncbi Analyses of PS integrin functions during Drosophila development
    S Zusman
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
    Development 118:737-50. 1993
    ..The location of the alternative exons suggests that the two forms of the PS beta integrin subunit may interact with alternative alpha subunits and/or ligands...
  43. ncbi Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle
    J T Yang
    Howard Hughes Medical Institute Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
    J Cell Biol 135:829-35. 1996
    ..Taking these results together, we conclude that alpha 4 integrins appear not to play essential roles in normal skeletal muscle development...
  44. ncbi A novel alpha integrin subunit associates with betaPS and functions in tissue morphogenesis and movement during Drosophila development
    K A Stark
    Howard Hughes Medical Institute and the Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Development 124:4583-94. 1997
    ..Phenotypic similarities suggest that laminin A is a potential ligand for this integrin, at least in some tissues...
  45. ncbi Requirements for integrins during Drosophila development
    S Zusman
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
    Development 108:391-402. 1990
    ..However, many other adhesive and morphogenetic processes proceed normally in the absence of integrins containing the beta subunit encoded by lethal(1)myospheroid...
  46. ncbi Dystrophic muscle in mice chimeric for expression of alpha5 integrin
    D Taverna
    Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Cell Biol 143:849-59. 1998
    ..However proper adhesion and survival of myoblasts on fibronectin was impaired. Our data suggest that a novel form of muscle dystrophy in mice is alpha5-integrin-dependent...
  47. ncbi A novel, tissue-specific integrin subunit, beta nu, expressed in the midgut of Drosophila melanogaster
    G H Yee
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
    Development 118:845-58. 1993
    ..Within this structure, beta v transcripts are especially concentrated in the cells of the midgut imaginal islands which give rise to the adult midgut...
  48. ncbi Alpha4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo
    A G Arroyo
    Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, Massachusetts 02139, USA
    Immunity 11:555-66. 1999
    ..In summary, alpha4 integrins are essential for normal development of all hematopoietic lineages in fetal liver, bone marrow, and spleen, likely by regulating the proliferation/differentiation balance of hematopoietic progenitors...
  49. ncbi Genomic analysis of metastasis reveals an essential role for RhoC
    E A Clark
    Howard Hughes Medical Institute, Centre for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 406:532-5. 2000
    ..The genomic approach allows us to identify families of genes involved in a process, not just single genes, and can indicate which molecular and cellular events might be important in complex biological processes such as metastasis...
  50. ncbi The cloning, genomic organization and expression of the focal contact protein paxillin in Drosophila
    G N Wheeler
    Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Gene 262:291-9. 2001
    ..The data support a role for paxillin as an adapter and/or signaling protein during developmental processes involving integrin-mediated adhesion...
  51. ncbi Organization of the fibronectin gene provides evidence for exon shuffling during evolution
    R S Patel
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    EMBO J 6:2565-72. 1987
    ..These data provide information pertinent to the transcriptional regulation of the gene, the alternative splicing of the primary transcript and the structure of the primary translation product...
  52. ncbi Xenopus laevis integrins. Structural conservation and evolutionary divergence of integrin beta subunits
    D W DeSimone
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139
    J Biol Chem 263:5333-40. 1988
    ..Despite the divergence in sequence among different integrin beta subunits, certain features of their structure are remarkably conserved...
  53. ncbi Multiple sites of alternative splicing of the rat fibronectin gene transcript
    J E Schwarzbauer
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    EMBO J 6:2573-80. 1987
    ..We report investigations designed to detect other regions of alternative splicing. We also show that the pattern of alternative splicing is somewhat altered on oncogenic transformation...
  54. ncbi Tumstatin, an endothelial cell-specific inhibitor of protein synthesis
    Yohei Maeshima
    Program in Matrix Biology, Department of Medicine and the Cancer Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Science 295:140-3. 2002
    ..These results establish a role for integrins in mediating cell-specific inhibition of cap-dependent protein synthesis and suggest a potential mechanism for tumstatin's selective effects on endothelial cells...
  55. ncbi Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins
    Adam Lacy-Hulbert
    Medical Research Council University of Edinburgh Centre for Inflammation Research, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
    Proc Natl Acad Sci U S A 104:15823-8. 2007
    ..Our results identify a vital role for myeloid alphav integrins in generating mucosal Treg cells and emphasize the importance of antigen-presenting cells in establishing immune tolerance...
  56. ncbi Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins
    Louise E Reynolds
    Cell Adhesion and Disease Laboratory, Richard Dimbleby Department, Imperial Cancer Research Fund, St Thomas Hospital, London, UK
    Nat Med 8:27-34. 2002
    ....
  57. ncbi Direct test of potential roles of EIIIA and EIIIB alternatively spliced segments of fibronectin in physiological and tumor angiogenesis
    Sophie Astrof
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell Biol 24:8662-70. 2004
    ..Our experiments show that despite their tight regulation during angiogenesis, the presence of EIIIA or EIIIB splice variants individually is not essential for neovascularization...
  58. ncbi Identification of the peptide sequences within the EIIIA (EDA) segment of fibronectin that mediate integrin alpha9beta1-dependent cellular activities
    Arti V Shinde
    Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA
    J Biol Chem 283:2858-70. 2008
    ..Our data provide a cellular activity for the EIIIA segment, evidence for conformational lability, and peptide sequences for probing EIIIA functions in vitro and in vivo...
  59. ncbi Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide?
    Sunny Y Wong
    Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cell Cycle 5:812-7. 2006
    ..Insights into tumor and stromal factors governing the intravasation process may help explain why certain tumors exhibit "preferred" pathways for metastatic dissemination, both clinically and in experimental animal models...
  60. ncbi Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin
    Yuki Hamano
    Center for Matrix Biology, Department of Medicine and Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Cancer Cell 3:589-601. 2003
    ..These results indicate that MMP-generated fragments of basement membrane collagen can have endogenous function as integrin-mediated suppressors of pathologic angiogenesis and tumor growth...
  61. ncbi Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere
    Charles A Whittaker
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Mol Biol Cell 13:3369-87. 2002
    ..These allow inferences about similar functions in novel situations such as protease regulators (e.g., complement factors and trypsin inhibitors) and intracellular proteins (e.g., helicases, chelatases, and copines)...
  62. ncbi Defective associations between blood vessels and brain parenchyma lead to cerebral hemorrhage in mice lacking alphav integrins
    Joseph H McCarty
    Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Mol Cell Biol 22:7667-77. 2002
    ..These data suggest a novel role for alphav integrins in the association between cerebral microvessels and central nervous system parenchymal cells...
  63. ncbi An interaction between {alpha}v{beta}8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain
    Joseph H McCarty
    Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 102:13479-83. 2005
    ..These data identify a previously uncharacterized interaction between an integrin and Band 4.1 family members and suggest an important functional role for alphavbeta8-Band 4.1 interactions in the development and maintenance of the CNS...
  64. ncbi Alpha4beta1 integrin and erythropoietin mediate temporally distinct steps in erythropoiesis: integrins in red cell development
    Shawdee Eshghi
    Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 177:871-80. 2007
    ....
  65. ncbi GPR56 and TG2: possible roles in suppression of tumor growth by the microenvironment
    Lei Xu
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cell Cycle 6:160-5. 2007
    ..The highly metastatic cells may escape from this inhibition by down-regulation of GPR56. Much future work will be needed to test this hypothesis and further our understanding of metastasis in general...
  66. ncbi Heart development in fibronectin-null mice is governed by a genetic modifier on chromosome four
    Sophie Astrof
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Mech Dev 124:551-8. 2007
    ..Identification of the modifier would significantly enhance our understanding of the molecular underpinning of heart development and disease...
  67. ncbi Protein 4.1B suppresses prostate cancer progression and metastasis
    Sunny Y Wong
    Howard Hughes Medical Institute, Massachusetts Institute of Technology Center for Cancer Research, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 104:12784-9. 2007
    ..1B as a negative regulator of cancer progression to metastatic disease...
  68. ncbi Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectin
    Sophie Astrof
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
    Dev Biol 311:11-24. 2007
    ..Our studies indicate that the presence or absence of EIIIA and EIIIB exons alters the function of FN and demonstrate the requirement for these alternatively spliced exons in cardiovascular development...
  69. ncbi Importance of donor- and recipient-derived selectins in cardiac allograft rejection
    Atsushi Izawa
    Transplantation Research Center, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Am Soc Nephrol 18:2929-36. 2007
    ..In conclusion, donor-derived selectins contribute to the development of both acute and chronic cardiac allograft rejection, and targeting donor selectins may open novel therapeutic approaches in clinical transplantation...
  70. ncbi Analyses of the role of endogenous SPARC in mouse models of prostate and breast cancer
    Sunny Y Wong
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Clin Exp Metastasis 25:109-18. 2008
    ....
  71. ncbi Genetic ablation of alphav integrins in epithelial cells of the eyelid skin and conjunctiva leads to squamous cell carcinoma
    Joseph H McCarty
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Am J Pathol 172:1740-7. 2008
    ....
  72. ncbi Gene expression changes in an animal melanoma model correlate with aggressiveness of human melanoma metastases
    Lei Xu
    Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, MA, USA
    Mol Cancer Res 6:760-9. 2008
    ..Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis...
  73. ncbi A system for Cre-regulated RNA interference in vivo
    Patrick Stern
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:13895-900. 2008
    ..These vector systems allow regulated combinatorial manipulation (both overexpression and loss of function) of gene expression in multiple systems in vitro and in vivo...
  74. ncbi GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis
    Lei Xu
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 103:9023-8. 2006
    ..We discuss the mechanisms whereby GPR56-TG2 interactions may suppress tumor growth and metastasis...
  75. ncbi Tumor-lymphatic interactions in an activated stromal microenvironment
    Sunny Y Wong
    Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biochem 101:840-50. 2007
    ....
  76. ncbi Structure-function analysis reveals discrete beta3 integrin inside-out and outside-in signaling pathways in platelets
    Zhiying Zou
    Division of Cardiology and Department of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Blood 109:3284-90. 2007
    ..These results reveal the presence of discrete bidirectional signaling pathways controlled by integrin beta subunits in platelets and describe a high-throughput means of further investigating these pathways in vivo...
  77. ncbi Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis
    Lubor Borsig
    Glycobiology Research and Training Center and the Cancer Center, Department of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Proc Natl Acad Sci U S A 99:2193-8. 2002
    ..Thus, L-selectin on neutrophils, monocytes, and/or NK cells has a role in facilitating metastasis, acting beyond the early time points wherein P-selectin mediates interactions of platelet with tumor cells...
  78. ncbi CD40L stabilizes arterial thrombi by a beta3 integrin--dependent mechanism
    Patrick Andre
    The Center for Blood Research, Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 8:247-52. 2002
    ..In addition, rsCD40L promoted the aggregation of either human or mouse platelets under high shear rates. Thus, CD40L appears to be an alphaIIbbeta3 ligand, a platelet agonist, and necessary for stability of arterial thrombi...
  79. ncbi Residues SFQ (173-175) in the large extracellular loop of CD9 are required for gamete fusion
    Guo Zhang Zhu
    Department of Cell Biology and Human Anatomy, School of Medicine, University of California Davis, Davis, CA 95616, USA
    Development 129:1995-2002. 2002
    ..These results suggest that SFQ in the CD9 large extracellular loop may be an active site which associates with and regulates the egg fusion machinery...
  80. ncbi Plasma fibronectin promotes thrombus growth and stability in injured arterioles
    Heyu Ni
    Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:2415-9. 2003
    ....
  81. ncbi Plasma levels of fibronectin bearing the alternatively spliced EIIIB segment are increased after major trauma
    John H Peters
    Department of Medicine, Veterans Affairs Northern California Health Care System, Sacramento Veterans Affairs Medical Center, Mather, California 95655, USA
    J Lab Clin Med 141:401-10. 2003
    ..Like EIIIA(+) forms of FN, EIIIB(+) FNs are recognized as soluble bloodborne markers for vascular tissue injury...
  82. ncbi Spirochete-platelet attachment and thrombocytopenia in murine relapsing fever borreliosis
    Kishore R Alugupalli
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Ave N, Worcester, MA 01655, USA
    Blood 102:2843-50. 2003
    ..These findings suggest that thrombocytopenia of relapsing fever is the result of platelet clearance after beta 3-independent bacterial attachment to circulating platelets...
  83. ncbi Central roles of alpha5beta1 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies
    Sheila E Francis
    Cardiovascular Research Group, University of Sheffield, Sheffield, UK
    Arterioscler Thromb Vasc Biol 22:927-33. 2002
    ..Thus, successful early vasculogenesis and angiogenesis require alpha5-FN interactions...
  84. ncbi Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins or selectins
    Daniela Taverna
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 101:763-8. 2004
    ..These results implicate cells of the innate immune system, macrophages or perhaps natural killer cells, in each case dependent on integrins and selectins, in tumor suppression...
  85. ncbi Selective ablation of alphav integrins in the central nervous system leads to cerebral hemorrhage, seizures, axonal degeneration and premature death
    Joseph H McCarty
    Center for Cancer Research, Massachusetts Institute of Technology, 40 Ames Street, E17 227, Cambridge, MA 02139, USA
    Development 132:165-76. 2005
    ....
  86. ncbi The spatial and temporal expression patterns of integrin alpha9beta1 and one of its ligands, the EIIIA segment of fibronectin, in cutaneous wound healing
    Purva Singh
    Center for Cell Biology and Cancer Research, Albany Medical College, Albany, New York, USA
    J Invest Dermatol 123:1176-81. 2004
    ..These observations suggest a role for alpha9beta1-EIIIA interactions in wound keratinocyte function...
  87. ncbi Complete replication of hepatitis C virus in cell culture
    Brett D Lindenbach
    Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 309:623-6. 2005
    ..HCVcc replication was inhibited by interferon-alpha and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals...
  88. ncbi Therapeutic expression of the platelet-specific integrin, alphaIIbbeta3, in a murine model for Glanzmann thrombasthenia
    Juan Fang
    Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Blood 106:2671-9. 2005
    ..These results indicate the feasibility of targeting platelets with genetic therapies for better management of patients with inherited bleeding disorders...
  89. ncbi Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis
    Sunny Y Wong
    Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, MA 02139, USA
    Cancer Res 65:9789-98. 2005
    ..These results suggest that tumor-secreted VEGF-C and, to a lesser extent, VEGF-A, are important for inducing prostate cancer intratumoral lymphangiogenesis but are unnecessary for lymph node metastasis...
  90. ncbi A direct test of potential roles for beta3 and beta5 integrins in growth and metastasis of murine mammary carcinomas
    Daniela Taverna
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cancer Res 65:10324-9. 2005
    ..These data indicate that alphavbeta3 or alphavbeta5 integrins are not essential for tumor growth and progression, although they might play some role in mammary gland development...
  91. ncbi Decreased plasma fibronectin leads to delayed thrombus growth in injured arterioles
    Jana Matuskova
    CBR Institute for Biomedical Research, Harvard Medical School, Boston, USA
    Arterioscler Thromb Vasc Biol 26:1391-6. 2006
    ..We were interested to study the thrombotic and hemostatic consequences of the decrease in plasma FN (pFN), the role of FN splice variants in thrombosis, and to examine whether pFN incorporates into thrombi in vivo...
  92. ncbi The echinoderm adhesome
    Charles A Whittaker
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Dev Biol 300:252-66. 2006
    ....
  93. ncbi The genome of the sea urchin Strongylocentrotus purpuratus
    Erica Sodergren
    Science 314:941-52. 2006
    ..This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes...
  94. ncbi Requirement for the NF-kappaB family member RelA in the development of secondary lymphoid organs
    Elizabeth Alcamo
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Exp Med 195:233-44. 2002
    ....

Research Grants33

  1. CELL SURFACE STRUCTURE AND TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 2000
    ..Such interactions play important roles in many aspects of normal physiology and in pathologies as diverse as wound healing, cancer, thrombosis, fibrosis and inflammation. ..
  2. CELL SURFACE STRUCTURE AND TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 2005
    ..Evaluation of the functions of cell adhesion proteins and the consequences of their misexpression in metastatic cells will lead to new leads for therapeutic interventions against metastasis. ..
  3. CELL SURFACE STRUCTURE AND TRANSFORMATION
    Richard Hynes; Fiscal Year: 1980
    ..Interactions between surface molecules and between the surface and the cytoskeleton will be studied as well as changes in these interactions caused by transformation. ..
  4. CELL SURFACE STRUCTURE AND TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 1993
    ..All these processes involve cell adhesion to extracellular matrices and molecules identical or closely related to those under study in this project...
  5. CELL SURFACE STRUCTURE AND CELL TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 1990
    ..This work should provide information relevant to the understanding of cell adhesion and migration and the role which these processes play in malignancy, hemostasis, thrombosis and embryological development...