John Hartwig

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function
    Hervé Falet
    Division of Translational Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 207:1967-79. 2010
  2. ncbi request reprint The birth of the platelet
    J Hartwig
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Thromb Haemost 1:1580-6. 2003
  3. ncbi request reprint The platelet: form and function
    John H Hartwig
    Division of Hematology, Karp Family Research Laboratories, Brigham and Women s Hospital, Boston, MA 02115, USA
    Semin Hematol 43:S94-100. 2006
  4. ncbi request reprint Cytoskeletal mechanisms for platelet production
    John H Hartwig
    Hematology Division, Brigham and Women s Hospital, 1 Blackfan Circle, Boston, MA 02115, USA
    Blood Cells Mol Dis 36:99-103. 2006
  5. doi request reprint Dual roles for hepatic lectin receptors in the clearance of chilled platelets
    Viktoria Rumjantseva
    Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 15:1273-80. 2009
  6. ncbi request reprint Ca2+ and calmodulin regulate the binding of filamin A to actin filaments
    Fumihiko Nakamura
    Hematology Division, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:32426-33. 2005
  7. ncbi request reprint Mechanisms and implications of platelet discoid shape
    Joseph E Italiano
    Division of Hematology and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Blood 101:4789-96. 2003
  8. ncbi request reprint In vitro function and phagocytosis of galactosylated platelet concentrates after long-term refrigeration
    Aleksandar M Babic
    Department of Pathology, Division of Translational Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Transfusion 47:442-51. 2007
  9. pmc WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells
    Alexander Kettner
    Division of Immunology, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 199:357-68. 2004
  10. pmc Disease-associated mutant alpha-actinin-4 reveals a mechanism for regulating its F-actin-binding affinity
    Astrid Weins
    Renal and Translational Medicine Divisions, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:16080-5. 2007

Research Grants

  1. REGULATION OF PLATELET SHAPE CHANGES
    John Hartwig; Fiscal Year: 2007
  2. REGULATION OF PLATELET SHAPE CHANGES
    John Hartwig; Fiscal Year: 2004
  3. REGULATION OF PLATELET SHAPE CHANGES
    John Hartwig; Fiscal Year: 2000

Collaborators

Detail Information

Publications47

  1. pmc A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function
    Hervé Falet
    Division of Translational Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 207:1967-79. 2010
    ..Our findings reveal that the interaction between FlnA and Syk regulates ITAM- and ITAM-like-containing receptor signaling and platelet function...
  2. ncbi request reprint The birth of the platelet
    J Hartwig
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Thromb Haemost 1:1580-6. 2003
    ..This phase occurs over a period of days and requires induction by megakaryocyte specific growth factors. Proplatelets are extended in the second phase and platelets are released. This phase is completed in hours...
  3. ncbi request reprint The platelet: form and function
    John H Hartwig
    Division of Hematology, Karp Family Research Laboratories, Brigham and Women s Hospital, Boston, MA 02115, USA
    Semin Hematol 43:S94-100. 2006
    ..In this review, we discuss the role of the cytoskeleton in defining the resting and active forms of the platelet...
  4. ncbi request reprint Cytoskeletal mechanisms for platelet production
    John H Hartwig
    Hematology Division, Brigham and Women s Hospital, 1 Blackfan Circle, Boston, MA 02115, USA
    Blood Cells Mol Dis 36:99-103. 2006
    ..How individual platelets form and release from proplatelets remains poorly understood...
  5. doi request reprint Dual roles for hepatic lectin receptors in the clearance of chilled platelets
    Viktoria Rumjantseva
    Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 15:1273-80. 2009
    ..Inhibition of chilled platelet clearance by both beta(2) integrin and Ashwell-Morell receptors may afford a potentially simple method for storing platelets in the cold...
  6. ncbi request reprint Ca2+ and calmodulin regulate the binding of filamin A to actin filaments
    Fumihiko Nakamura
    Hematology Division, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:32426-33. 2005
    ..These findings identify the first evidence for direct regulation of FLNa, implicating a mechanism whereby Ca(2+)-calmodulin selectively targets the FLNa.F-actin complex...
  7. ncbi request reprint Mechanisms and implications of platelet discoid shape
    Joseph E Italiano
    Division of Hematology and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Blood 101:4789-96. 2003
    ..Together, these findings highlight the essential requirements of the MK/platelet-restricted beta1-tubulin isoform in platelet structure and suggest that spherocytosis does not impair many aspects of platelet function...
  8. ncbi request reprint In vitro function and phagocytosis of galactosylated platelet concentrates after long-term refrigeration
    Aleksandar M Babic
    Department of Pathology, Division of Translational Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Transfusion 47:442-51. 2007
    ..PLT-associated galactosyltransferase efficiently galactosylates chilled PLTs in the presence of its substrate UDP-galactose is added to PLT-rich plasma...
  9. pmc WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells
    Alexander Kettner
    Division of Immunology, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 199:357-68. 2004
    ..These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement...
  10. pmc Disease-associated mutant alpha-actinin-4 reveals a mechanism for regulating its F-actin-binding affinity
    Astrid Weins
    Renal and Translational Medicine Divisions, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:16080-5. 2007
    ....
  11. ncbi request reprint Role for phosphoinositide 3-kinase in Fc gamma RIIA-induced platelet shape change
    Kurt L Barkalow
    Division of Hematology, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Am J Physiol Cell Physiol 285:C797-805. 2003
    ....
  12. pmc Alpha-adducin dissociates from F-actin and spectrin during platelet activation
    Kurt L Barkalow
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 161:557-70. 2003
    ....
  13. ncbi request reprint WIP participates in actin reorganization and ruffle formation induced by PDGF
    Ines M Anton
    Division of Immunology, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Cell Sci 116:2443-51. 2003
    ..These data suggest a role for WIP in actin reorganization to form PDGF-induced ruffles. This is the first in vivo evidence in mammalian cells for a function of WIP dependent on its ability to bind actin...
  14. ncbi request reprint WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation
    Ines M Anton
    Division of Immunology, Children s Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Immunity 16:193-204. 2002
    ..Both WIP-deficient T and B cells show a profound defect in their subcortical actin filament networks. These results suggest that WIP is important for immunologic synapse formation and T cell activation...
  15. ncbi request reprint Filling gaps in signaling to actin cytoskeletal remodeling
    Thomas P Stossel
    Hematology Division, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA
    Dev Cell 4:444-5. 2003
    ..It describes the identification of a novel membrane component Mig-2 that engages filamin A through a new intermediary, migfilin, to stimulate actin assembly and cell spreading on a substrate of extracellular matrix...
  16. pmc The biogenesis of platelets from megakaryocyte proplatelets
    Sunita R Patel
    Hematology Division, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 115:3348-54. 2005
    ..This Review will describe the process of platelet assembly in detail and discuss several disorders that affect platelet production...
  17. ncbi request reprint The macrophage alphaMbeta2 integrin alphaM lectin domain mediates the phagocytosis of chilled platelets
    Emma C Josefsson
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:18025-32. 2005
    ....
  18. ncbi request reprint FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling
    Yasutaka Ohta
    Hematology Division, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Nat Cell Biol 8:803-14. 2006
    ..FilGAP is, therefore, a mediator of the well-established antagonism of Rac by RhoA that suppresses leading edge protrusion and promotes cell retraction to achieve cellular polarity...
  19. ncbi request reprint Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin
    Teresia M Osborn
    Translational Medicine Division Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    Am J Physiol Cell Physiol 292:C1323-30. 2007
    ..024). Therefore, pGSN interferes with PAF- and LPA-induced cellular activation in vitro, suggesting a mechanism for the protective role of pGSN in vivo...
  20. pmc Structural basis of filamin A functions
    Fumihiko Nakamura
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 179:1011-25. 2007
    ..Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high-angle FLNa/F-actin branching resistant to bending by thermal forces, and high avidity F-actin binding and cross-linking...
  21. ncbi request reprint SALS, a WH2-domain-containing protein, promotes sarcomeric actin filament elongation from pointed ends during Drosophila muscle growth
    Jianwu Bai
    Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Dev Cell 13:828-42. 2007
    ....
  22. pmc Platelet-associated IgAs and impaired GPVI responses in platelets lacking WIP
    Hervé Falet
    Division of Translational Medicine, Brigham and Women s Hospital, One Blackfan Cir, Karp 6, Boston, MA02115, USA
    Blood 114:4729-37. 2009
    ..Together, the data indicate that platelet-associated IgAs negatively modulate GPVI signaling and function in WIP KO mice...
  23. pmc Molecular basis of filamin A-FilGAP interaction and its impairment in congenital disorders associated with filamin A mutations
    Fumihiko Nakamura
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    PLoS ONE 4:e4928. 2009
    ..Mutations in filamin A (FLNa), an essential cytoskeletal protein with multiple binding partners, cause developmental anomalies in humans...
  24. ncbi request reprint Normal Arp2/3 complex activation in platelets lacking WASp
    Hervé Falet
    Department of Medicine, Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, LMRC 301, Boston, MA 02115, USA
    Blood 100:2113-22. 2002
    ..Taken together, our findings show that platelets activate Arp2/3 complex, assemble actin, and change shape in the absence of WASp, indicating a more specialized role for WASp in these cells...
  25. ncbi request reprint Glycosylation restores survival of chilled blood platelets
    Karin M Hoffmeister
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Science 301:1531-4. 2003
    ..Platelet-associated galactosyltransferase produces efficient galactosylation when uridine diphosphate-galactose is added, affording a potentially simple method for storing platelets in the cold...
  26. pmc Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes
    Sunita R Patel
    Division of Hematology, Brigham and Women s Hospital, Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Blood 106:4076-85. 2005
    ..We conclude that while continuous polymerization of microtubules is necessary to support the enlarging proplatelet mass, the sliding of overlapping microtubules is a vital component of proplatelet elongation...
  27. ncbi request reprint Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets
    Wolfgang Bergmeier
    The CBR Institute for Biomedical Research, Inc, 800 Huntington Ave, Boston, MA 02115, USA
    Blood 102:4229-35. 2003
    ..Surface expression of GPIbalpha might be a powerful marker to determine the quality of platelet concentrates, because it reflects metalloproteinase activity in vitro...
  28. ncbi request reprint Integrin alpha(IIb)beta3 signals lead cofilin to accelerate platelet actin dynamics
    Hervé Falet
    Division of Hematology, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, One Blackfan Circle, Karp 6, Boston, Massachusetts 02115, USA
    Am J Physiol Cell Physiol 289:C819-25. 2005
    ..Our results suggest that cofilin is essential for actin dynamics mediated by outside-in signals in activated platelets...
  29. pmc Importance of free actin filament barbed ends for Arp2/3 complex function in platelets and fibroblasts
    Hervé Falet
    Division of Hematology, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, 221 Longwood Avenue, LMRC 301, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:16782-7. 2002
    ..We conclude that Arp23 complex contribution to actin filament nucleation in platelets and fibroblasts importantly requires free barbed ends generated by severing and uncapping...
  30. ncbi request reprint The clearance mechanism of chilled blood platelets
    Karin M Hoffmeister
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cell 112:87-97. 2003
    ..Chilled platelets bind vWf and function normally in vitro and ex vivo after transfusion into CR3-deficient mice. Therefore, GPIb modification might permit cold platelet storage...
  31. pmc The structure of the GPIb-filamin A complex
    Fumihiko Nakamura
    Hematology Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 107:1925-32. 2006
    ..To verify the topology of GPIb-FLNa interaction we also purified the native complex from platelets and showed that GPIb interacts with the C-terminus of FLNa, which is in accordance with our biochemical and structural data...
  32. pmc Mechanisms of organelle transport and capture along proplatelets during platelet production
    Jennifer L Richardson
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 106:4066-75. 2005
    ..These studies demonstrate that the components that form platelets are delivered to and assembled de novo along proplatelets...
  33. ncbi request reprint Delivering new insight into the biology of megakaryopoiesis and thrombopoiesis
    Elisabeth M Battinelli
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Curr Opin Hematol 14:419-26. 2007
    ..The aim of this review is to explore the state of the art knowledge on the cell biological and molecular pathways that regulate megakaryopoiesis and lead to platelet production...
  34. pmc Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules
    Sunita Patel-Hett
    Translational Medicine Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Blood 111:4605-16. 2008
    ..Thus, the dynamic microtubules associated with the marginal band likely function during both resting and activated platelet states...
  35. pmc Arp2/3 complex-deficient mouse fibroblasts are viable and have normal leading-edge actin structure and function
    Alessia Di Nardo
    Division of Hematology, Brigham and Women s Hospital, and Department of Medicine, Harvard Medical School, One Blackfan Circle, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:16263-8. 2005
    ..The Arp2/3 complex can be dispensable for leading-edge actin remodeling...
  36. pmc WIP is critical for T cell responsiveness to IL-2
    Severine Le Bras
    Division of Immunology, Children s Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:7519-24. 2009
    ..These results indicate that WIP is essential for IL-2 signaling and responsiveness in T cells, possibly because of its critical role in TCR-triggered actin cytoskeletal reorganization...
  37. ncbi request reprint Cell surface actin remodeling
    Thomas P Stossel
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Cell Sci 119:3261-4. 2006
  38. ncbi request reprint Endothelial actin cytoskeleton remodeling during mechanostimulation with fluid shear stress
    Eric A Osborn
    Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Am J Physiol Cell Physiol 290:C444-52. 2006
    ..We conclude that shear stress initiates a cytoplasmic actin-remodeling response that is used for endothelial cell shape change instead of bulk cell translocation...
  39. pmc Activating mutations of N-WASP alter Shigella pathogenesis
    David A Adamovich
    Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA
    Biochem Biophys Res Commun 384:284-9. 2009
    ..However, plaque numbers were increased in cells expressing N-WASP L229P and L232P. These data demonstrate that N-WASP structural conformation is an important regulator of Shigella pathogenesis in distinct segments of its lifecycle...
  40. doi request reprint GLUT4 vesicle recruitment and fusion are differentially regulated by Rac, AS160, and Rab8A in muscle cells
    Varinder K Randhawa
    Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    J Biol Chem 283:27208-19. 2008
    ....
  41. pmc Protein 4.1R-dependent multiprotein complex: new insights into the structural organization of the red blood cell membrane
    Marcela Salomao
    Red Cell Physiology Laboratory and Membrane Biochemistry Laboratory, New York Blood Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 105:8026-31. 2008
    ....
  42. ncbi request reprint Dynamic regulation of microtubule coils in ADP-induced platelet shape change by p160ROCK (Rho-kinase)
    Benjamin Z S Paul
    Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Platelets 14:159-69. 2003
    ..Continued disruption of the cytoskeletal microtubule ring, appears to be a Rhokinase-dependent event involved in the transformation of discoid platelets into spheres...
  43. ncbi request reprint Signaling pathways of the F11 receptor (F11R; a.k.a. JAM-1, JAM-A) in human platelets: F11R dimerization, phosphorylation and complex formation with the integrin GPIIIa
    Malgorzata B Sobocka
    Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA
    J Recept Signal Transduct Res 24:85-105. 2004
    ....
  44. pmc Actin and septin ultrastructures at the budding yeast cell cortex
    Avital A Rodal
    Department of Biology, Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454, USA
    Mol Biol Cell 16:372-84. 2005
    ..These images provide the first high-resolution views of septin organization in cells...
  45. pmc Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton
    Theodosia A Kalfa
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC 7015, Cincinnati, OH 45229, USA
    Blood 108:3637-45. 2006
    ..Thus, deficiency of Rac1 and Rac2 GTPases in mice alters actin assembly in RBCs and causes microcytic anemia with reticulocytosis, implicating Rac GTPases as dynamic regulators of the erythrocyte cytoskeleton organization...
  46. ncbi request reprint Galactosylation does not prevent the rapid clearance of long-term, 4 degrees C-stored platelets
    Hans H Wandall
    ZymeQuest, Beverly, MA, USA
    Blood 111:3249-56. 2008
    ..We conclude that different mechanisms of clearance may exist for short- and long-term cold-stored platelets...
  47. pmc Loss of PIP5KIbeta demonstrates that PIP5KI isoform-specific PIP2 synthesis is required for IP3 formation
    Yanfeng Wang
    Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 105:14064-9. 2008
    ..These results also demonstrate that after stimulation of a G protein-coupled receptor, IP(3) is completely derived from a rapidly synthesized discrete pool of PIP(2) synthesized by PIP5KIalpha and PIP5KIbeta...

Research Grants12

  1. REGULATION OF PLATELET SHAPE CHANGES
    John Hartwig; Fiscal Year: 2007
    ..abstract_text> ..
  2. REGULATION OF PLATELET SHAPE CHANGES
    John Hartwig; Fiscal Year: 2004
    ..In the last aim, we will identify, purify and characterize factors that activate platelet Arp2/3 downstream of cdc42. ..
  3. REGULATION OF PLATELET SHAPE CHANGES
    John Hartwig; Fiscal Year: 2000
    ..The location of the signal transduction proteins, PI-3 kinase, GPIIb/IIIa, and tensin in resting and active platelet cytoskeleton will be determined to see if complex formation occurs during activation. ..