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Genomes and Genes | T P StosselSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Regulation of financial conflicts of interest in medical practice and medical research: a damaging solution in search of a problemThomas P Stossel
Department of Medicine, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
Perspect Biol Med 50:54-71. 2007..Most ominously, it has imposed onerous and counterproductive regulations on medical education and translational research...
Filamins as integrators of cell mechanics and signallingT P Stossel
Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Nat Rev Mol Cell Biol 2:138-45. 2001..They integrate cellular architectural and signalling functions and are essential for fetal development and cell locomotion. Here, we describe the history, structure and function of this group of proteins...
Mechanical strain in actin networks regulates FilGAP and integrin binding to filamin AA J Ehrlicher
Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 478:260-3. 2011..These results identify a molecular mechanotransduction element within the actin cytoskeleton, revealing that mechanical strain of key proteins regulates the binding of signalling molecules...
Mechanisms of cold-induced platelet actin assemblyK M Hoffmeister
Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA
J Biol Chem 276:24751-9. 2001....
Filamin A, the Arp2/3 complex, and the morphology and function of cortical actin filaments in human melanoma cellsL A Flanagan
Hematology Division, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
J Cell Biol 155:511-7. 2001..Contrary to some proposals, Arp2/3 complex-mediated branching of actin alone is insufficient for establishing an orthogonal actin organization or maintaining mechanical stability at the leading edge...
Deconstructing gelsolin: identifying sites that mimic or alter binding to actin and phosphoinositidesP A Janmey
Experimental Medicine Division, Brigham and Women s Hospital, Boston, MA 02115, USA
Chem Biol 5:R81-5. 1998..Recent advances in defining the structure of gelsolin identified functionally important sites. These structural insights could lead to the design of small molecule analogs to enhance, inhibit or mimic the functions of gelsolin...
Thiol oxidation of actin produces dimers that enhance the elasticity of the F-actin networkJ X Tang
Hematology Division, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Biophys J 76:2208-15. 1999..These new findings may explain why previous studies of actin rheology report a wide range of values when purified actin is polymerized without added regulatory proteins...
Cell permeant polyphosphoinositide-binding peptides that block cell motility and actin assemblyC C Cunningham
Hematology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 276:43390-9. 2001..This class of reagents confirms the critical relation between inositol lipids and cytoskeletal structure and may be useful to probe the location and function of polyphosphoinositides in vivo...
Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheetsG Fenteany
Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Curr Biol 10:831-8. 2000..We have used epithelial wound closure as a model system for such movements and examined the mechanisms of closure and the importance of the Rho family of Ras-related small GTPases in this process...
Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cellsA Marti
Diabetes Unit and Medical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 021291, USA
J Biol Chem 272:2620-8. 1997..ABP-280 participates in TNF-alpha signal transduction to SAPKs, in part through the binding of SEK-1...
Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolinW Witke
Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Cell 81:41-51. 1995..Neither gelsolin nor other proteins with similar actin filament-severing activity are expressed in early embryonic cells, indicating that this mechanism of actin filament dynamics is not essential for motility during early embryogenesis...
Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolinC A Vasconcellos
Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115
Science 263:969-71. 1994..These results suggest that gelsolin may have therapeutic potential as a mucolytic agent in CF patients...
Mechanisms of lysolipid phosphate effects on cellular survival and proliferationE J Goetzl
Department of Medicine, University of California, San Francisco 94143, USA
Ann N Y Acad Sci 905:177-87. 2000....
Comparison of filamin A-induced cross-linking and Arp2/3 complex-mediated branching on the mechanics of actin filamentsFumihiko Nakamura
Hematology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 277:9148-54. 2002..They suggest complementary roles for actin branching and cross-linking in cellular actin mechanics in vivo...
The structure of the GPIb-filamin A complexFumihiko 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...
FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodellingYasutaka 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...
Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolinTeresia 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...
Plasma gelsolin is a marker and therapeutic agent in animal sepsisPo Shun Lee
Pulmonary and Critical Care Division Brigham and Women s Hospital, Boston, MA, USA
Crit Care Med 35:849-55. 2007..Depletion of plasma gelsolin in systemic inflammation may contribute to adverse outcomes. We examined the role of plasma gelsolin in animal models of sepsis...
In vitro function and phagocytosis of galactosylated platelet concentrates after long-term refrigerationAleksandar 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...
Disease-associated mutant alpha-actinin-4 reveals a mechanism for regulating its F-actin-binding affinityAstrid 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....
Structural basis of filamin A functionsFumihiko 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...
Has the hunt for conflicts of interest gone too far? YesThomas P Stossel
Department of Medicine, Harvard Medical School, Translational Medicine and Hematology Divisions, Brigham and Women s Hospital, 1 Blackfan Circle, Karp 6, Boston, MA 02115 USA
BMJ 336:476. 2008
Arp2/3 complex-deficient mouse fibroblasts are viable and have normal leading-edge actin structure and functionAlessia 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...
Effect of thrombopoietin alone and a combination of cytochalasin B and ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid-AM on the survival and function of autologous baboon platelets stored at 4 degrees C for as long as 5 daysC Robert Valeri
Naval Blood Research Laboratory, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Transfusion 44:865-70. 2004....
Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1Ratna K Vadlamudi
Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Nat Cell Biol 4:681-90. 2002....
Importance of free actin filament barbed ends for Arp2/3 complex function in platelets and fibroblastsHervé 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...
The clearance mechanism of chilled blood plateletsKarin 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...
Filling gaps in signaling to actin cytoskeletal remodelingThomas 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...
Glycosylation restores survival of chilled blood plateletsKarin 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...
Ribosomal S6 kinase (RSK) regulates phosphorylation of filamin A on an important regulatory siteMichele S Woo
Department of Cell Biology, Brigham and Women s Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 24:3025-35. 2004..Given that phosphorylation of FLNa on Ser(2152) is required for Pak1-mediated membrane ruffling, our results suggest a novel role for RSK in the regulation of the actin cytoskeleton...
The macrophage alphaMbeta2 integrin alphaM lectin domain mediates the phagocytosis of chilled plateletsEmma 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....
Ca2+ and calmodulin regulate the binding of filamin A to actin filamentsFumihiko 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...
Cell surface actin remodelingThomas P Stossel
Hematology Division, Brigham and Women's Hospital, Boston, MA 02115, USA
J Cell Sci 119:3261-4. 2006
Recombinant plasma gelsolin diminishes the acute inflammatory response to hyperoxia in miceMelpo Christofidou-Solomidou
Division of Pulmonary Medicine, Department of Medicine, University of Pennsylvania Medical School, Philadelphia, USA
J Investig Med 50:54-60. 2002..03). CONCLUSIONS: These data imply that i) gelsolin depletion contributes to the pathogenesis of oxygen toxicity and ii) repletion of gelsolin can partially abrogate the resultant exudative response...
A biopsy of financial conflicts of interest in medicineThomas P Stossel
Divisions of Translational Medicine and Hematology, Brigham and Women's Hospital, Boston, Mass, USA
Surgery 143:193-8. 2008
Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantationMark J DiNubile
Division of Infectious Diseases, Department of Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Camden, NJ, USA
Blood 100:4367-71. 2002..0007). These findings suggest that gelsolin levels shortly after allogeneic HSCT can predict the later development of fatal IPS. Gelsolin replacement in selected transplant patients may offer a novel strategy to prevent or reverse IPS...
Divergent views on managing clinical conflicts of interestThomas P Stossel
Mayo Clin Proc 82:1013-4; author reply 1014-5. 2007
Overregulation of conflicts hinders medical progressThomas P Stossel
Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
Cleve Clin J Med 74:S14-5; discussion S16-22. 2007..Regulations to prevent conflicts of interest by restricting medical education, medical research, expert advisory functions, or researcher ownership of inventions may have the unintended consequence of slowing medical progress...
Relationship of plasma gelsolin levels to outcomes in critically ill surgical patientsPo-Shun Lee
Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA, USA
Ann Surg 243:399-403. 2006..CONCLUSION: Plasma gelsolin is a potential prognostic biomarker for critically ill surgical patients. Plasma gelsolin replacement may have therapeutic application...
Regulating academic-industrial research relationships--solving problems or stifling progress?Thomas P Stossel
Harvard Medical School and the Hematology Division, Brigham and Women s Hospital, Boston, USA
N Engl J Med 353:1060-5. 2005
