Flaumenhaft Lab: Research
The Flaumenhaft laboratory studies fundamental problems in platelet biology that are of clinical importance. We focus on the use of emerging technologies to evaluate poorly understood aspects of platelet function. We also use novel imaging strategies to elucidate the interaction of platelets with thrombi in vivo.
TRAINING PHILOSOPHY
An important goal of the laboratory is to create a training environment that is at once scientifically rigorous, intellectually intense, and fun. The scientific maturation of each laboratory member is a priority of the Principle Investigator. Academic development of lab members is accomplished in part by didactics. It is also achieved by fostering the productivity of each lab member, since productivity in biological sciences is an essential component of successful development.
Projects
Molecular Mechanisms of Platelet Granule Secretion
Chemical Genetic Analysis of Platelet Activation
Physiology of Platelet Microparticles
Techniques
Techniques used for these projects include flow cytometry, immunoblot analysis, subcellular fractionation, fluorescence microscopy, platelet aggregation and granule release assays, cell permeabilization assays, actin polymerization assays, 2D electrophoresis, mass spectroscopy, and thin layer chromatography. We also work with murine models of thrombus formation using digital videomicroscopy.
Technologies
- Intravital microscopy
- High throughput screening
- Novel flow cytometry methods
through collaborations:
- Electron microscopy
- Near Infrared Imaging
- Laser optical tweezers
- Megakaryocyte cell culture
Collaborators
Dvorak laboratory
Frangioni laboratory
Furie laboratory
Golan laboratory
Institute of Chemistry and Cell Biology
Division of Experiment Medicine at Brighams and Womens Hospital
Funding
The Flaumenhaft laboratory has been supported by generous funding from the following organizations:
NIH (National Heart, Lung, and Blood Institute)
Howard Hughes Medical Institute
Burroughs Wellcome Foundation
CITP, Pfizer
American Society of Hematology
Charitable Leadership Foundation
Bayer Biological Products
Awards and Honors
1996 Postdoctoral Research Fellowship for Physicians, Howard Hughes Medical Institute
1997 Travel Award, American Society of Hematology
1998 Travel Award, American Society of Hematology
1999 Clinical Investigator Track Program, Awardee
1999 Burroughs Wellcome Fund Career Award
2002 American Society of Hematology Junior Faculty Scholar Award
2005 Special Project Award, Bayer Biological Products
Publications
Flaumenhaft R, Furie B, and Furie BC. alpha-Granule secretion from a-toxin permeabilized, MgATP-primed platelets is induced independently by H+ and Ca2+. J Cell Physiol.1999; 179: 1-10.
Flaumenhaft R, Croce K, Chen E, Furie BC, and Furie B. Proteins of the exocytotic core complex mediate platelet a- granule secretion: Roles of vesicle-associated membrane protein, SNAP-23, and syntaxin 4. J Biol Chem. 1999; 274:2492-2501.
Thorpe CM, Flaumenhaft R, Hurley BS, Jacewicz M, Acheson DW, and Keusch GT. Shiga toxins from the enterohemorrhagic E. coli do not directly stimulate alpha-granule secretion or enhance aggregation of human platelets. Acta Hematol. 1999, 102: 51-55.
Yang J, Hirata T, Croce K, Merrill-Skoloff G, Tchernychev B, Williams E, Flaumenhaft R, Furie BC, and Furie B. Targeted gene disruption demonstrates that PSGL-1 is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration. J Exp Med. 1999; 190: 1769-1782.
Croce K, Flaumenhaft R, Rivers M, Furie B, Furie BC, Herman I, and Potter DA. Inhibition of calpain blocks platelet secretion, aggregation, and spreading. J Biol Chem. 1999; 274: 36321- 36327.
Feng D, Flaumenhaft R, Bandeira-Melo C, Weller P, and Dvorak A. Ultrastructural localization of vesicle-associated membrane protein(s) to specialized membrane structures in human pericytes, vascular smooth muscle cells, endothelial cells, neutrophils, and eosinophils. J Histochem Cytochem. 2001; 49: 293-304.
Rozenvayn N and Flaumenhaft R. Phosphatidylinositol (4,5)-bisphosphate mediates Ca2+-induced platelet alpha-granule secretion: Evidence for type II phosphatidylinositol 5-phosphate 4-kinase-dependent function. J Biol Chem. 2001; 276: 22410-9.
Feng D, Crane K, Rozenvayn N, Dvorak AM, and Flaumenhaft R. Subcellular distribution of three functional platelet SNARE proteins: Human Cellubrevin, SNAP-23, and syntaxin 2. Blood. 2002; 99: 4006-4014.
Rozenvayn N and Flaumenhaft R. Protein kinase C mediates translocation of type II phosphatidylinositol 5-phosphate 4-kinase required for platelet alpha-granule secretion. J Biol Chem. 2003; 278(10): 8126-34.
Lai KC and Flaumenhaft R. SNARE protein degradation upon platelet activation: Calpain cleaves SNAP-23. J Cell Physiol. 2003; 194(2): 206-214.
Flaumenhaft, R and Sim DS. The platelet as a model for chemical genetics. Chem Biol. 2003; 10: 481-486.
Flaumenhaft R. The molecular basis of platelet granule secretion. Arterioscler Thromb Vasc Biol. 2003; 23(7):1152-1160.
Celi A, Merrill-Skoloff G, Gross P, Falati S, Sim D, Flaumenhaft R, Furie BC, Furie B. Thrombus formation: Direct real time observation and digital analysis of thrombus assembly in a living mouse by confocal and widefield intravital microscopy. J Thromb Haemost. 2003; 1: 60-68.
Sim DS, Merrill-Skoloff G, Furie BC, Furie B, and Flaumenhaft R. Initial accumulation of platelets during arterial thrombus formation in vivo is inhibited by elevation of basal cAMP levels. Blood. 2004; 103: 2127-2134.
O’Connell DJ, Rozenvayn N, and Flaumenhaft R. Phosphatidylinositol (4,5)-bisphosphate regulates activation-induced platelet microparticle formation. Biochemistry. 2005; 26: 44(16):6361-70.
Flaumenhaft R, Dilks J, Rozenvayn N, Monahan-Earley RA, Feng D, and Dvorak AM. The actin cytoskeleton differentially regulates platelet alpha-granule and dense granule secretion Blood. 2005; 105(10):3879-87.
