VASCULAR RELATIONS OF BLOOD CELLS AND PROTEINS

Summary

Principal Investigator: Richard E Waugh
Abstract: The theme of this program project is the inter-relation of mechanics, chemistry and hydrodynamics as underlying mechanisms in normal and pathological peripheral vascular function, particularly the inflammatory response. Five projects are engaged in synergistic studies designed to reveal fundamental mechanisms underlying both normal and pathological phenomena in the peripheral vasculature with a central focus on neutrophil-endothelial interactions. Projects 1, 2, 3 and 4 have a common focus and employ complementary approaches to understand what governs integrin-mediated neutrophil attachment and migration. A particular emphasis is to relate behaviors observed in vitro (Projects 1, 2 and 3), where we can obtain precise understanding of regulatory mechanisms of adhesion, to clinically relevant events in vivo (Projects 2 and 4). Project 1 uses quantitative models and molecular approaches to understand signaling events connecting chemokine stimulus to integrin activation and cell immobilization in flow, as well as experiments on force generation during neutrophil crawling (with Projects 2 and 3). Project 2 uses molecular approaches to learn how integrin affinity is regulated in distinct regions of migrating cells both in vitro and in vivo. Project 3 uses single cell experiments to reveal how molecular diffusion and surface topography affect adhesion and the initiation of cell crawling, and to characterize the dynamics of signaling pathways leading to changes in integrin affinity and avidity. Project 4 focuses on the mechanisms underlying leukocyte-endothelial interaction in vivo, with emphasis on the functional consequences of heterogeneities in adhesion molecule expression, and signaling events in endothelial cells (EC) initiated by leukocyte ligation. Project 5 uses both computational and experimental approaches to study mechanisms related to cell capture, particularly with respect to ways that multiparticle hydrodynamics and shear stress may affect cell capture and cell activation (with Projects 1 and 4). In addition to computational studies to determine consequences of abnormal cell geometry on cell capture. Project 5, with Project 3, is exploring mechanotransduction mechanisms affecting L-selectin shedding and neutrophil response to agonists via G-protein coupled receptors. Peripheral vascular dysfunction is integral to pathology associated with the most serious diseases in western society, including heart disease, stroke, and cancer metastasis, as well as disorders involving inflammation and immunity. The underlying mechanisms for these involve mechanical forces, molecular interactions and cellular properties acting synergistically in ways that are uniquely addressed by this program.
Funding Period: 1997-07-01 - 2015-06-30
more information: NIH RePORT

Top Publications

  1. pmc Fluid shear stress increases neutrophil activation via platelet-activating factor
    Michael J Mitchell
    Department of Biomedical Engineering, Cornell University, Ithaca, New York
    Biophys J 106:2243-53. 2014
  2. pmc Leukocyte rolling and adhesion both contribute to regulation of microvascular permeability to albumin via ligation of ICAM-1
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, New York 14642, USA
    Am J Physiol Cell Physiol 301:C804-13. 2011
  3. pmc Role of c-Abl in L-selectin shedding from the neutrophil surface
    Carissa J Ball
    Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA
    Blood Cells Mol Dis 46:246-51. 2011
  4. pmc LFA-1 and Mac-1 define characteristically different intralumenal crawling and emigration patterns for monocytes and neutrophils in situ
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    J Immunol 185:7057-66. 2010
  5. pmc Neutrophil adhesion and chemotaxis depend on substrate mechanics
    Risat A Jannat
    Department of Bioengineering University of Pennsylvania, Philadelphia, PA 19104, USA
    J Phys Condens Matter 22:194117. 2010
  6. pmc Control of volume-sensitive chloride channel inactivation by the coupled action of intracellular chloride and extracellular protons
    Carmen Y Hernandez-Carballo
    Instituto de Fisica, Universidad Autonoma de San Luis Potosi, Ave Dr Manuel Nava 6, San Luis Potosi, San Luis Potosi, SLP 78290, Mexico
    Pflugers Arch 460:633-44. 2010
  7. pmc Intercellular adhesion molecule-1 enrichment near tricellular endothelial junctions is preferentially associated with leukocyte transmigration and signals for reorganization of these junctions to accommodate leukocyte passage
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    J Immunol 184:5242-52. 2010
  8. pmc Image correlation microscopy for uniform illumination
    T R Gaborski
    Department of Biomedical Engineering, School of Engineering Applied Science, University of Rochester, Rochester, NY 14627, USA
    J Microsc 237:39-50. 2010
  9. pmc Activated protein C action in inflammation
    Pranita P Sarangi
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Br J Haematol 148:817-33. 2010
  10. pmc Outside-in signal transmission by conformational changes in integrin Mac-1
    Craig T Lefort
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA
    J Immunol 183:6460-8. 2009

Research Grants

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
  2. Discovery and Development of Therapeutic Genes for CHF
    H Kirk Hammond; Fiscal Year: 2013
  3. Elafin Therapy for Lung Diseases
    Marlene Rabinovitch; Fiscal Year: 2013
  4. ADAPTATIONS TO HYPOXIA
    Kurt R Stenmark; Fiscal Year: 2013
  5. Glycan Modulation of Inflammatory Responses
    Ajit P Varki; Fiscal Year: 2013
  6. Immune-Based Interventions Against Infectious Diseases
    Alan L Rothman; Fiscal Year: 2013
  7. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
  8. Digitalis-Induced Signaling by Cardiac Na+/K+-ATPase
    Amir Askari; Fiscal Year: 2013
  9. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
  10. Neurohumoral control of veins in hypertension
    Gregory D Fink; Fiscal Year: 2013

Detail Information

Publications59

  1. pmc Fluid shear stress increases neutrophil activation via platelet-activating factor
    Michael J Mitchell
    Department of Biomedical Engineering, Cornell University, Ithaca, New York
    Biophys J 106:2243-53. 2014
    ..These results indicate that fluid shear stress exposure increases neutrophil activation by PAF, and, taken together with previous observations, differentially controls how neutrophils respond to chemoattractants...
  2. pmc Leukocyte rolling and adhesion both contribute to regulation of microvascular permeability to albumin via ligation of ICAM-1
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, New York 14642, USA
    Am J Physiol Cell Physiol 301:C804-13. 2011
    ..This study thus identifies a new mechanism by which antiadhesion treatment may constitute a potential therapy for tissue edema...
  3. pmc Role of c-Abl in L-selectin shedding from the neutrophil surface
    Carissa J Ball
    Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA
    Blood Cells Mol Dis 46:246-51. 2011
    ..This study sheds light on the role of c-Abl in neutrophil adhesion not previously reported in the literature...
  4. pmc LFA-1 and Mac-1 define characteristically different intralumenal crawling and emigration patterns for monocytes and neutrophils in situ
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    J Immunol 185:7057-66. 2010
    ..Thus, mechanisms underlying leukocyte crawling are important in regulating the inflammatory responses by regulating the numbers of leukocytes that transmigrate...
  5. pmc Neutrophil adhesion and chemotaxis depend on substrate mechanics
    Risat A Jannat
    Department of Bioengineering University of Pennsylvania, Philadelphia, PA 19104, USA
    J Phys Condens Matter 22:194117. 2010
    ..These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation...
  6. pmc Control of volume-sensitive chloride channel inactivation by the coupled action of intracellular chloride and extracellular protons
    Carmen Y Hernandez-Carballo
    Instituto de Fisica, Universidad Autonoma de San Luis Potosi, Ave Dr Manuel Nava 6, San Luis Potosi, San Luis Potosi, SLP 78290, Mexico
    Pflugers Arch 460:633-44. 2010
    ..The model depicts inactivation as a pore constriction that happens by simultaneous binding of H(+) and Cl(-) ions to the channel followed by a voltage-dependent conformational change that ultimately causes inactivation...
  7. pmc Intercellular adhesion molecule-1 enrichment near tricellular endothelial junctions is preferentially associated with leukocyte transmigration and signals for reorganization of these junctions to accommodate leukocyte passage
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    J Immunol 184:5242-52. 2010
    ..6- and 2.6-fold, respectively). Taken together, these data identify an important role for EC morphology and expression patterns of ICAM-1 in leukocyte transmigration...
  8. pmc Image correlation microscopy for uniform illumination
    T R Gaborski
    Department of Biomedical Engineering, School of Engineering Applied Science, University of Rochester, Rochester, NY 14627, USA
    J Microsc 237:39-50. 2010
    ..Additionally, we demonstrate uniform illumination image correlation microscopy analysis of adhesion molecule domain aggregation and diffusion on the surface of human neutrophils...
  9. pmc Activated protein C action in inflammation
    Pranita P Sarangi
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Br J Haematol 148:817-33. 2010
    ..Therefore, the cytoprotective effects, rather than the anticoagulant effect of APC are postulated to be responsible for the therapeutic benefit of APC in the treatment of severe sepsis...
  10. pmc Outside-in signal transmission by conformational changes in integrin Mac-1
    Craig T Lefort
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA
    J Immunol 183:6460-8. 2009
    ..These data suggest the primacy of global conformational changes in the generation of Mac-1 outside-in signals...
  11. pmc Cell adhesion molecule distribution relative to neutrophil surface topography assessed by TIRFM
    Sandrine A Hocdé
    Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
    Biophys J 97:379-87. 2009
    ..The results confirm differences among adhesion molecules in their surface distribution and reveal how the availability of specific adhesion molecules is altered by mechanical compression of the surface in live cells...
  12. pmc Traction forces of neutrophils migrating on compliant substrates
    Risat A Jannat
    Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Biophys J 101:575-84. 2011
    ..In summary, neutrophils display a diverse repertoire of methods for organizing their internal machinery to generate directional motion...
  13. pmc Toxoplasma gondii triggers release of human and mouse neutrophil extracellular traps
    Delbert S Abi Abdallah
    Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA
    Infect Immun 80:768-77. 2012
    ..We propose that NET formation limits infection by direct microbicidal effects on Toxoplasma as well as by interfering with the ability of the parasite to invade target host cells...
  14. pmc Role of β1 integrin in tissue homing of neutrophils during sepsis
    Pranita P Sarangi
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, NY 14642, USA
    Shock 38:281-7. 2012
    ....
  15. pmc Optogenetic control of chemokine receptor signal and T-cell migration
    Yuexin Xu
    Department of Microbiology and Immunology and David H Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642
    Proc Natl Acad Sci U S A 111:6371-6. 2014
    ..These findings suggest that the use of photoactivatable chemokine receptors allows remotely controlled leukocyte trafficking with outstanding spatial resolution in tissues and may be feasible in other cell transfer therapies. ..
  16. ncbi Ligand density elicits a phenotypic switch in human neutrophils
    Steven J Henry
    Department of Bioengineering, University of Pennsylvania, 210 S 33rd St, Philadelphia, PA 19104, USA
    Integr Biol (Camb) 6:348-56. 2014
    ..These results suggest that neutrophils are capable of displaying multiple modes of motility as dictated by their adhesive environment. ..
  17. ncbi Dynamics of adhesion molecule domains on neutrophil membranes: surfing the dynamic cell topography
    Thomas R Gaborski
    Department of Biomedical Engineering, University of Rochester, Rochester, NY, 14627, USA
    Eur Biophys J 42:851-5. 2013
    ..The diffusion of pre-assembled integrin domains to zones of neutrophil/endothelial contact may provide a mechanism to facilitate high avidity adhesion during the earliest stages of firm arrest. ..
  18. pmc Stem cell enrichment with selectin receptors: mimicking the pH environment of trauma
    Thong M Cao
    Department of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA
    Sensors (Basel) 13:12516-26. 2013
    ..These results suggest that mimicking the acidic conditions of trauma can induce a conformational extension of L-selectin, which can be utilized for flow-based, clinical isolation of HSPCs. ..
  19. pmc Isolation of αL I domain mutants mediating firm cell adhesion using a novel flow-based sorting method
    Lauren R Pepper
    Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Protein Eng Des Sel 26:515-21. 2013
    ..Characterization of these mutants supports a greater understanding of the structure-function relationship of the αL I domain, and of the relationship between applied force and bioadhesion in a broader context. ..
  20. pmc Emerging understanding of roles for arterioles in inflammation
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, Rochester, New York, USA
    Microcirculation 20:679-92. 2013
    ....
  21. pmc Deformable cell-cell and cell-substrate interactions in semi-infinite domain
    Dhananjay Radhakrishnan Subramaniam
    Department of Mechanical Engineering, Rochester Institute of Technology, Rochester, NY 14623, USA
    J Biomech 46:1067-74. 2013
    ..As a result of cell compliance, rolling velocity may decrease significantly, compared to non-compliant cells...
  22. pmc Decreased Krev interaction-trapped 1 expression leads to increased vascular permeability and modifies inflammatory responses in vivo
    Maripat Corr
    University of Rochester, Department of Pharmacology and Physiology, 601 Elmwood Ave, Box 711, Rochester, NY 14642, USA
    Arterioscler Thromb Vasc Biol 32:2702-10. 2012
    ..Here, we investigate the role of Krev interaction-trapped 1 (KRIT1), an adherens junction accessory protein required for cell-cell junction stability, in regulating these vascular functions...
  23. pmc Uropod elongation is a common final step in leukocyte extravasation through inflamed vessels
    Young Min Hyun
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA
    J Exp Med 209:1349-62. 2012
    ..These findings suggest that uropod elongation is a final step in the leukocyte extravasation cascade, which may be important for precise regulation of leukocyte recruitment into inflamed tissues...
  24. pmc Opposing roles for RhoH GTPase during T-cell migration and activation
    Christina M Baker
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA
    Proc Natl Acad Sci U S A 109:10474-9. 2012
    ..Thus, we conclude that RhoH expression provides a key molecular determinant that allows T cells to switch between sensing chemokine-mediated go signals and TCR-dependent stop signals...
  25. pmc Molecular accessibility in relation to cell surface topography and compression against a flat substrate
    Sandrine A Hocdé
    Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
    Biophys J 97:369-78. 2009
    ..Model predictions show good agreement with measurements of fluorescence intensity of different molecules labeled fluorescently on the surface of a human neutrophil compressed against a glass surface...
  26. pmc Activated integrin VLA-4 localizes to the lamellipodia and mediates T cell migration on VCAM-1
    Young Min Hyun
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, NY 14642, USA
    J Immunol 183:359-69. 2009
    ..These data suggest that a subpopulation of activated VLA-4 is mainly localized to the leading edge of polarized human T cells and is critical for T cell migration on VCAM-1...
  27. pmc Adhesive dynamics simulations of the mechanical shedding of L-selectin from the neutrophil surface
    Dooyoung Lee
    Department of Bioengineering, University of Pennsylvania, 19104, USA
    J Theor Biol 260:27-30. 2009
    ..In summary, we show through detailed computational modeling that the force-dependent shedding of L-selectin can explain the rolling behavior of neutrophils mediated by L-selectin in vitro...
  28. pmc Adhesive dynamics simulation of neutrophil arrest with stochastic activation
    Ellen F Krasik
    Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Biophys J 95:1716-28. 2008
    ....
  29. pmc Role of gp120 trimerization on HIV binding elucidated with Brownian adhesive dynamics
    Andrew D Trister
    Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Biophys J 95:40-53. 2008
    ..On long timescales, all gp120 in the contact area will become bound to CD4. We found that it takes seconds for engaged trimers to cluster CD4 molecules in the contact zone, which partially explains the deleay in viral entry...
  30. pmc Microvascular endothelial cells exhibit optimal aspect ratio for minimizing flow resistance
    Ronen Sumagin
    Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USA
    Ann Biomed Eng 36:580-5. 2008
    ..These results raise the question of whether less organized circulatory systems, such as that found in newly formed solid tumors or in the developing embryo, may deviate from the optimal bump spacing predicted to minimize flow resistance...
  31. pmc Shear-induced capping of L-selectin on the neutrophil surface during centrifugation
    Dooyoung Lee
    Department of Chemical Engineering, University of Rochester, Rochester, NY 14627, USA
    J Immunol Methods 328:97-105. 2007
    ....
  32. pmc Do blood capillaries exhibit optimal bumpiness?
    Michael R King
    J Theor Biol 249:178-80. 2007
  33. ncbi A role for ICAM-1 in maintenance of leukocyte-endothelial cell rolling interactions in inflamed arterioles
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    Am J Physiol Heart Circ Physiol 293:H2786-98. 2007
    ....
  34. ncbi Hypertonicity induced apoptosis in HL-60 cells in the presence of intracellular potassium
    Arko Ghosh
    Neuroscience Undergraduate Program, Trinity College, Hartford, CT 06106, USA
    Apoptosis 12:1281-8. 2007
    ..Apoptosis was initiated in hypertonic conditions consisting of high intracellular K(+). We demonstrate that apoptosis can occur in the presence of high intracellular potassium contrary to previous predictions...
  35. ncbi Mechanical shedding of L-selectin from the neutrophil surface during rolling on sialyl Lewis x under flow
    Dooyoung Lee
    Department of Chemical Engineering, University of Rochester, Rochester, New York 14642, USA
    J Biol Chem 282:4812-20. 2007
    ..Thus, these data show that mechanical force induces the cleavage of L-selectin from the neutrophil surface during rolling and therefore decreases the adhesion of cells to a ligand-presenting surface in flow...
  36. pmc Interplay between shear stress and adhesion on neutrophil locomotion
    Lee A Smith
    Department of Chemical and Biomolecular Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Biophys J 92:632-40. 2007
    ..Our findings illustrate that the endothelium may regulate neutrophil migration in postcapillary venules through the presentation of various adhesion ligands at sites of inflammation...
  37. ncbi Dynamics of increased neutrophil adhesion to ICAM-1 after contacting immobilized IL-8
    Elena B Lomakina
    Department of Pharmacology and Physiology, University of Rochester, Medical Center, Rochester, 601 Elmwood Avenue, Box 711, NY 14642, USA
    Ann Biomed Eng 34:1553-63. 2006
    ..Heterogeneity in the cellular response and variability between donors was also noted...
  38. pmc Spreading of neutrophils: from activation to migration
    Kheya Sengupta
    Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA
    Biophys J 91:4638-48. 2006
    ..The different spreading regimes correspond to distinct values of the exponent b and are related to the adhesion state of the cell. Treatment with cytochalasin-B eliminated the anisotropy in the spreading...
  39. pmc TNF-alpha activation of arterioles and venules alters distribution and levels of ICAM-1 and affects leukocyte-endothelial cell interactions
    Ronen Sumagin
    Dept of Pharmacology and Physiology, Univ of Rochester, Medical Center, Box 711, Rochester, NY 14642, USA
    Am J Physiol Heart Circ Physiol 291:H2116-25. 2006
    ..That arteriolar ECs respond to TNF-alpha by upregulation of ICAM-1, although in a different way compared with venules, suggests an explicit role for arterioles in inflammatory responses...
  40. pmc Na+ modulates anion permeation and block of P2X7 receptors from mouse parotid glands
    Juan Pablo Reyes
    Instituto de Fisica, Universidad Autonoma de San Luis Potosi, Dr Manuel Nava 6, San Luis Potosi, SLP 78290, Mexico
    J Membr Biol 223:73-85. 2008
    ..Thus, our data indicate that P2X7R is fundamental for I(ATPCl) generation in acinar cells and that external Na+ modulates ion permeability and conductivity, as well as drug affinity, in P2X7R...
  41. pmc Leukocyte-endothelial cell interactions are linked to vascular permeability via ICAM-1-mediated signaling
    Ronen Sumagin
    Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA
    Am J Physiol Heart Circ Physiol 295:H969-H977. 2008
    ..We conclude that ICAM-1 plays an essential role in the regulation of Ps in microvessels and that there are two separate (constitutive and inducible) signaling pathways that regulate permeability under normal and inflamed conditions...
  42. pmc Inhibition of Na+/H+ exchanger enhances low pH-induced L-selectin shedding and beta2-integrin surface expression in human neutrophils
    Nubia K Kaba
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, USA
    Am J Physiol Cell Physiol 295:C1454-63. 2008
    ..Taken together, these data suggest that the ability of NHE inhibitors such as HMA to reduce ischemia-reperfusion injury may be related to the nearly complete removal of L-selectin from the neutrophil surface...
  43. pmc A separate role for ICAM-1 and fluid shear in regulating leukocyte interactions with straight regions of venular wall and venular convergences
    Ronen Sumagin
    Department of Pharmacology and Physiology, University of Rochester, New York, USA
    Microcirculation 16:508-20. 2009
    ..Here, we dissected the effects of each of these factors on leukocyte behavior in different venular regions...
  44. pmc Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia
    Griselda Casas-Pruneda
    School of Medicine, Universidad Autonoma de San Luis Potosi, San Luis Potosi, SLP, Mexico
    J Physiol 587:2887-901. 2009
    ..03 mM. Taken together our observations indicate a functional interaction between murine P2X7 and P2X4 receptors. Such interaction might occur in acinar cells to shape the response to extracellular ATP in salivary epithelia...
  45. pmc Adhesive dynamics simulation of G-protein-mediated chemokine-activated neutrophil adhesion
    Kelly E Caputo
    Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Biophys J 96:2989-3004. 2009
    ....
  46. pmc Vessel diameter measurement from intravital microscopy
    Jaesung Lee
    School of Electrical and Computer Engineering, Cornell University, 357 Rhodes Hall, Ithaca, NY 14850, USA
    Ann Biomed Eng 37:913-26. 2009
    ..The experiment with 10 synthetic videos and 20 intravital microscopy videos, including 10 fluorescence confocal and 10 non-confocal transmission, shows that the measurement can be performed accurately...
  47. pmc Activation of human neutrophil Mac-1 by anion substitution
    Elena Lomakina
    Department of Pharmacology and Physiology, School of Medicine, University of Rochester, Rochester, NY 14642, USA
    Blood Cells Mol Dis 42:177-84. 2009
    ..This effect is substantial. The percentage of Mac-1 in the high affinity state approaches 100% in glutamate and 50% in glucuronate, a far greater response than what is observed after stimulation with fMLP...
  48. pmc Recombinant human activated protein C inhibits integrin-mediated neutrophil migration
    Gwendolyn F Elphick
    Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence, RI, USA
    Blood 113:4078-85. 2009
    ..Thus, we conclude that leukocyte integrins are novel cellular receptors for rhAPC and the interaction decreases neutrophil recruitment into tissues, providing a potential mechanism by which rhAPC may protect against sepsis...
  49. ncbi Microcontact printing of P-selectin increases the rate of neutrophil recruitment under shear flow
    Dooyoung Lee
    Dept of Chemical Engineering, University of Rochester, Rochester, NY 14627, USA
    Biotechnol Prog 24:1052-9. 2008
    ..It is concluded that microCP may be a more general technique to control protein orientation on a substrate...
  50. pmc Leukocyte integrins and their ligand interactions
    Young Min Hyun
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, NY 14642, USA
    Immunol Res 45:195-208. 2009
    ..However, current therapeutics broadly affect integrin functions and, thus, yield unfavorable side effects. This review discusses the major leukocyte integrins and the anti-adhesion strategies for treating immune diseases...
  51. pmc Lack of coupling between membrane stretching and pannexin-1 hemichannels
    Juan P Reyes
    Institute of Physics, Universidad Autonoma de San Luis Potosi, Dr Manuel Nava 6, San Luis Potosi, SLP 78290, Mexico
    Biochem Biophys Res Commun 380:50-3. 2009
    ..We conclude that carbenoxolone directly inhibited I(Cl,swell) independent of pannexin-1 and that pannexin-1 hemichannels are not activated by swelling in HEK-293 cells...
  52. pmc Adhesion between human neutrophils and immobilized endothelial ligand vascular cell adhesion molecule 1: divalent ion effects
    Elena B Lomakina
    Department of Pharmacology and Physiology, University of Rochester, Medical Center, Rochester, New York, USA
    Biophys J 96:276-84. 2009
    ..The results indicate that the first step is rate limiting for VLA-4-VCAM-1 interactions. Changing divalent cation composition affects these coefficients, implicating molecular conformational changes as a key step in the process...
  53. pmc Active site formation, not bond kinetics, limits adhesion rate between human neutrophils and immobilized vascular cell adhesion molecule 1
    Richard E Waugh
    Department of Biomedical Engineering, University of Rochester, Medical Center, Rochester, New York, USA
    Biophys J 96:268-75. 2009
    ....
  54. pmc Selectin catch-slip kinetics encode shear threshold adhesive behavior of rolling leukocytes
    Michael T Beste
    Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 105:20716-21. 2008
    ..Collectively, our results extend the conceptual framework of adhesive dynamics as a means to translate complex single-molecule biophysics to macroscopic cell behavior...
  55. pmc Macromolecule permeability of in situ and excised rodent skeletal muscle arterioles and venules
    Ingrid H Sarelius
    Dept of Pharmacology and Physiology, Univ of Rochester Medical Center, Box 711, Rochester, NY 14642, USA
    Am J Physiol Heart Circ Physiol 290:H474-80. 2006
    ....

Research Grants30

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..
  2. Discovery and Development of Therapeutic Genes for CHF
    H Kirk Hammond; Fiscal Year: 2013
    ..Four Cores will support the Program: Digital Imaging (Dr. Farquhar);Vector Production (Dr. Miyanohara);Translational Systems (Dr. Hammond) and Clinical &Administrative (Dr. Hammond). ..
  3. Elafin Therapy for Lung Diseases
    Marlene Rabinovitch; Fiscal Year: 2013
    ..The Administrative Core facilitates exchange of information and postdoctoral training in Lung Translational Medicine, and facilitates our strategy to move elafin into clinical trial in the next cycle. ..
  4. ADAPTATIONS TO HYPOXIA
    Kurt R Stenmark; Fiscal Year: 2013
    ..abstract_text> ..
  5. Glycan Modulation of Inflammatory Responses
    Ajit P Varki; Fiscal Year: 2013
    ..abstract_text> ..
  6. Immune-Based Interventions Against Infectious Diseases
    Alan L Rothman; Fiscal Year: 2013
    ..3. Recruit promising junior investigators and provide mentoring by established NIH-funded researchers. 4. Support a multidisciplinary research program led by junior investigators in translational infectious diseases immunology. ..
  7. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
    ..abstract_text> ..
  8. Digitalis-Induced Signaling by Cardiac Na+/K+-ATPase
    Amir Askari; Fiscal Year: 2013
    ..abstract_text> ..
  9. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
    ..A major objective of this Program Project is to inform decisions of the IPF Clinical Network by providing information that can be translated into novel therapeutic strategies for IPF. ..
  10. Neurohumoral control of veins in hypertension
    Gregory D Fink; Fiscal Year: 2013
    ..This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins. ..
  11. New Approaches To Cardiothoracic Tolerance Induction
    Joren C Madsen; Fiscal Year: 2013
    ..We anticipate ongoing progress will continue to contribute to a reduction in the morbidity and mortality associated with solid organ transplantation. ..