S L Diamond

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc Steady-state kinetic modeling constrains cellular resting states and dynamic behavior
    Jeremy E Purvis
    Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS Comput Biol 5:e1000298. 2009
  2. pmc Pairwise agonist scanning predicts cellular signaling responses to combinatorial stimuli
    Manash S Chatterjee
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Biotechnol 28:727-32. 2010
  3. pmc Systems biology of coagulation
    S L Diamond
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Thromb Haemost 11:224-32. 2013
  4. ncbi request reprint Microfluidics and coagulation biology
    Thomas V Colace
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Annu Rev Biomed Eng 15:283-303. 2013
  5. pmc Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient
    Ryan W Muthard
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Lab Chip 13:1883-91. 2013
  6. pmc Direct observation of von Willebrand factor elongation and fiber formation on collagen during acute whole blood exposure to pathological flow
    Thomas V Colace
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 33:105-13. 2013
  7. pmc Blood clots are rapidly assembled hemodynamic sensors: flow arrest triggers intraluminal thrombus contraction
    Ryan W Muthard
    Department of Chemical and Biomolecular Engineering, Vagelos Research Laboratory, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 32:2938-45. 2012
  8. pmc Thrombus growth and embolism on tissue factor-bearing collagen surfaces under flow: role of thrombin with and without fibrin
    Thomas V Colace
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratories, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 32:1466-76. 2012
  9. pmc Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice
    Katarzyna Leszczynska
    Department of Diagnostic Microbiology, Medical University of Bialystok, 15 230 Bialystok, Poland
    BMC Microbiol 9:187. 2009
  10. pmc Tissue factor activity under flow
    Scott L Diamond
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Thromb Res 125:S29-30. 2010

Research Grants

  1. Blood Systems Biology
    Scott L Diamond; Fiscal Year: 2010
  2. Multiplexed HTS of Serine and Cysteine Proteases (RMI)
    Scott Diamond; Fiscal Year: 2005
  3. Mechanisms of Cardiopulmonary Gene Transfer
    Scott Diamond; Fiscal Year: 2006
  4. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2007
  5. Blood Systems Biology
    Scott Diamond; Fiscal Year: 2007
  6. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2009
  7. Mechanisms of Cardiopulmonary Gene Transfer
    Scott L Diamond; Fiscal Year: 2010
  8. Mechanisms of Cardiopulmonary Gene Transfer
    Scott Diamond; Fiscal Year: 2005
  9. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2005
  10. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2004

Collaborators

Detail Information

Publications88

  1. pmc Steady-state kinetic modeling constrains cellular resting states and dynamic behavior
    Jeremy E Purvis
    Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS Comput Biol 5:e1000298. 2009
    ..To demonstrate application of the method, we show how small kinetic perturbations in a modular model of platelet P2Y(1) signaling can cause widespread compensatory effects on cellular resting states...
  2. pmc Pairwise agonist scanning predicts cellular signaling responses to combinatorial stimuli
    Manash S Chatterjee
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Biotechnol 28:727-32. 2010
    ..Training neural networks with pairs of stimuli across the dose-response regime represents an efficient approach for predicting complex signal integration in a patient-specific disease milieu...
  3. pmc Systems biology of coagulation
    S L Diamond
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Thromb Haemost 11:224-32. 2013
    ..Along with '-omics' data sets, such advanced models seek to predict the multifactorial range of healthy responses and diverse bleeding and clotting scenarios, ultimately to understand and improve patient outcomes. ..
  4. ncbi request reprint Microfluidics and coagulation biology
    Thomas V Colace
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Annu Rev Biomed Eng 15:283-303. 2013
    ..Overall, microfluidic advances offer many opportunities for research, drug testing under relevant hemodynamic conditions, and clinical diagnostics. ..
  5. pmc Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient
    Ryan W Muthard
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Lab Chip 13:1883-91. 2013
    ..This microfluidic design allows investigation of the coupled processes of platelet deposition and thrombin/fibrin generation in the presence of controlled transthrombus permeation and wall shear stress...
  6. pmc Direct observation of von Willebrand factor elongation and fiber formation on collagen during acute whole blood exposure to pathological flow
    Thomas V Colace
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 33:105-13. 2013
    ..In severe stenosis, von Willebrand factor (vWF) experiences millisecond exposures to pathological wall shear rates (γ(w)). We sought to evaluate the deposition of vWF onto collagen surfaces under flow in these environments...
  7. pmc Blood clots are rapidly assembled hemodynamic sensors: flow arrest triggers intraluminal thrombus contraction
    Ryan W Muthard
    Department of Chemical and Biomolecular Engineering, Vagelos Research Laboratory, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 32:2938-45. 2012
    ..A microfluidic device capable of flowing human blood over a side channel plugged with collagen (± tissue factor) was used to measure thrombus permeability (κ) and contraction at controlled transthrombus pressure drops...
  8. pmc Thrombus growth and embolism on tissue factor-bearing collagen surfaces under flow: role of thrombin with and without fibrin
    Thomas V Colace
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratories, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 32:1466-76. 2012
    ..Using microfluidic flow devices as well as patterned surfaces of collagen and tissue factor (TF), we sought to determine the role that fibrin plays in clot stability without interfering with the production of thrombin...
  9. pmc Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice
    Katarzyna Leszczynska
    Department of Diagnostic Microbiology, Medical University of Bialystok, 15 230 Bialystok, Poland
    BMC Microbiol 9:187. 2009
    ..pylori potential of cathelicidin LL-37 peptide, which is naturally present in gastric juice, its optimized synthetic analog WLBU2, and the non-peptide antibacterial agent ceragenin CSA-13...
  10. pmc Tissue factor activity under flow
    Scott L Diamond
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Thromb Res 125:S29-30. 2010
    ..Such in vitro perfusion systems also allow a determination of the potency of anti-platelet agents as a function of wall shear rate...
  11. pmc Harry L. Goldsmith, Ph.d
    Scott L Diamond
    University of Pennsylvania, Philadelphia, PA, USA
    Ann Biomed Eng 36:523-6. 2008
  12. doi request reprint Systems biology to predict blood function
    S L Diamond
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Thromb Haemost 7:177-80. 2009
    ..For clinical applications, the systems biology prediction of patient-specific pharmacological response requires the final assembly of platelet intracellular metabolism models with coagulation protease network models...
  13. doi request reprint Proteases' prime targets revealed
    Scott L Diamond
    Department of Chemical Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratories, Philadelphia, Pennsylvania 19104 6383, USA
    Nat Biotechnol 26:652-3. 2008
  14. ncbi request reprint Methods for mapping protease specificity
    Scott L Diamond
    Penn Center for Molecular Discovery, Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, 1024 Vagelos Research Laboratories, University of Pennsylvania, Philadelphia PA 19104, USA
    Curr Opin Chem Biol 11:46-51. 2007
    ..These new methods continue to inform the design of chemical inhibitors and the identification of substrates of proteases...
  15. ncbi request reprint Engineering design of optimal strategies for blood clot dissolution
    S L Diamond
    Institute for Medicine and Engineering, Department of Chemical Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Annu Rev Biomed Eng 1:427-62. 1999
    ..These principles also impact the design and analysis of local delivery devices...
  16. ncbi request reprint Biodegradable polyglycolide endovascular coils promote wall thickening and drug delivery in a rat aneurysm model
    J M Abrahams
    Department of Neurosurgery, Silverstein 5, The Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
    Neurosurgery 49:1187-93; discussion 1193-5. 2001
    ..BPCs were also tested for use in local drug delivery...
  17. pmc Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L
    Parag P Shah
    Penn Center for Molecular Discovery, University of Pennsylvania, 1024 Vagelos Laboratories, Philadelphia, PA 19104 6383, USA
    Mol Pharmacol 74:34-41. 2008
    ..In addition, the thiocarbazate inhibited in vitro propagation of malaria parasite Plasmodium falciparum with an IC(50) of 15.4 microM and inhibited Leishmania major with an IC(50) of 12.5 microM...
  18. pmc Thrombin flux and wall shear rate regulate fibrin fiber deposition state during polymerization under flow
    K B Neeves
    Department of Chemical Engineering, Colorado School of Mines, Golden, Colorado, USA
    Biophys J 98:1344-52. 2010
    ..For Da > 900 and Pe < 100, we observed three-dimensional gels. These results indicate that increases in wall shear rate quench first lateral aggregation and then protofibril extension...
  19. ncbi request reprint Shear stress causes nuclear localization of endothelial glucocorticoid receptor and expression from the GRE promoter
    Julie Y Ji
    Institute for Medicine and Engineering, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Circ Res 92:279-85. 2003
    ....
  20. ncbi request reprint Neutrophil enhancement of fibrin deposition under flow through platelet-dependent and -independent mechanisms
    M S Goel
    Institute for Medicine and Engineering, Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104, USA
    Arterioscler Thromb Vasc Biol 21:2093-8. 2001
    ..Neutrophils can interact with platelets via released proteases to increase platelet procoagulant activity and fibrin formation in CTI-treated plasma under the low-flow conditions expected in venous thrombosis or inflammation...
  21. pmc Design, synthesis, and evaluation of inhibitors of cathepsin L: Exploiting a unique thiocarbazate chemotype
    Michael C Myers
    Penn Center for Molecular Discovery, University of Pennsylvania, 1024 Vagelos Research Laboratories, Philadelphia, PA 19104 6383, USA
    Bioorg Med Chem Lett 18:3646-51. 2008
    ..Molecular docking studies using coordinates of a papain-inhibitor complex as a model for cathepsin L provided useful insights...
  22. pmc Neutrophil-bead collision assay: pharmacologically induced changes in membrane mechanics regulate the PSGL-1/P-selectin adhesion lifetime
    K E Edmondson
    Institute for Medicine and Engineering, Department of Bioengineering, University of Pennsylvania, 3320 Smith Walk, Philadelphia, PA 19104, USA
    Biophys J 89:3603-14. 2005
    ..Membrane tether growth can be enhanced or reduced pharmacologically with consequent effects on PSGL-1/P-selectin lifetimes...
  23. ncbi request reprint Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear-resistance of platelet aggregates
    K B Neeves
    Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Thromb Haemost 6:2193-201. 2008
    ..Flow chambers allow the ex vivo study of platelet response to defined surfaces at controlled wall shear stresses. However, most assays require 1-10 mL of blood and are poorly suited for murine whole blood experiments...
  24. doi request reprint Interplay between membrane cholesterol and ethanol differentially regulates neutrophil tether mechanics and rolling dynamics
    M Furlow
    Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Biorheology 48:49-64. 2011
    ..Overall, ethanol attenuated cholesterol-induced adhesion increases while increasing membrane fluidity as indicated by tether length...
  25. ncbi request reprint Adhesion of normal erythrocytes at depressed venous shear rates to activated neutrophils, activated platelets, and fibrin polymerized from plasma
    Mukul S Goel
    Department of Chemical Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia 19104, USA
    Blood 100:3797-803. 2002
    ..Endothelial activation and unusually low flow may be a setting prone to receptor-mediated RBC adhesion to adherent neutrophils (or platelets/fibrin), all of which may contribute to DVT...
  26. ncbi request reprint Neutrophil cathepsin G promotes prothrombinase and fibrin formation under flow conditions by activating fibrinogen-adherent platelets
    Mukul S Goel
    Institute for Medicine and Engineering, Department of Chemical Engineering, University of Pennsylvania, 1010 Vagelos Research Laboratories, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 278:9458-63. 2003
    ..However, further activation inhibition studies indicated that cathepsin G enhances fibrin deposition under flow conditions by elevating the activation state of fibrinogen-adherent platelets rather than by cleaving coagulation factors...
  27. doi request reprint P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditions
    S F Maloney
    Department of Chemical and Biomolecular Engineering, Division of Hematology and Oncology, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratories, University of Pennsylvania, Philadelphia, PA 19104, USA
    Integr Biol (Camb) 2:183-92. 2010
    ..This technique provides a platform for rapidly investigating effects of antithrombotic therapies simultaneously in a model injury system...
  28. ncbi request reprint Factor VIIa-mediated tenase function on activated platelets under flow
    M S Goel
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA
    J Thromb Haemost 2:1402-10. 2004
    ..Tissue factor (TF) and/or active factor (F)VIIa may be stored inside resting platelets...
  29. pmc Multiscale systems biology and physics of thrombosis under flow
    Mathew H Flamm
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA
    Ann Biomed Eng 40:2355-64. 2012
    ..These simulations accommodate particular flow geometries, blood phenotype, pharmacological regimen, and reactive surfaces to help predict disease risk or response to therapy...
  30. doi request reprint Endothelial cell specific adhesion molecule (ESAM) localizes to platelet-platelet contacts and regulates thrombus formation in vivo
    T J Stalker
    Department of Medicine, The Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Thromb Haemost 7:1886-96. 2009
    ..In resting platelets, endothelial cell specific adhesion molecule (ESAM) is located in alpha granules, increasing its cell surface expression following platelet activation. However, the function of ESAM on platelets is unknown...
  31. ncbi request reprint Exogenous nitric oxide activates the endothelial glucocorticoid receptor
    Julie Y Ji
    Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratory, 3340 Smith Walk, Philadelphia, PA 19104, USA
    Biochem Biophys Res Commun 318:192-7. 2004
    ..Overall, exogenous NO from high concentration donors can directly activate GR, suggesting a potential feedback mechanism for NO to regulate endothelial inducible nitric oxide synthase (iNOS) expression...
  32. pmc Combined antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugate
    Robert Bucki
    Department of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Antimicrob Agents Chemother 54:2525-33. 2010
    ..The combined antibacterial and anti-inflammatory activities of D2S suggest its potential as an alternative to natural CAPs in the prevention and treatment of some bacterial infections...
  33. pmc Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry
    Graham Simmons
    Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:11876-81. 2005
    ..The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection...
  34. ncbi request reprint Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagents
    Jeffrey A Gruneich
    Department of Bioengineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Gene Med 9:381-91. 2007
    ....
  35. pmc Molecular docking of cathepsin L inhibitors in the binding site of papain
    Mary Pat Beavers
    Penn Center for Molecular Discovery, Institute for Medicine and Engineering, and Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Chem Inf Model 48:1464-72. 2008
    ....
  36. ncbi request reprint Surfactants attenuate gas embolism-induced thrombin production
    David M Eckmann
    Department of Anesthesia and the Institute for Medicine and Engineering, University of Pennsylvania, Philadephia, 19104, USA
    Anesthesiology 100:77-84. 2004
    ..The authors conducted experiments to measure thrombin production in sheared whole blood in the presence and absence of bubbles and three surface-active compounds...
  37. doi request reprint High-throughput screening for modulators of mesenchymal stem cell chondrogenesis
    ALICE H HUANG
    McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA
    Ann Biomed Eng 36:1909-21. 2008
    ..These studies demonstrate our ability to carry out high-throughput screening assays for modulators of chondrogenesis...
  38. doi request reprint Analysis of morphology of platelet aggregates formed on collagen under laminar blood flow
    T Colace
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratories, University of Pennsylvania, Philadelphia, PA 19104, USA
    Ann Biomed Eng 39:922-9. 2011
    ..Microfluidic devices in combination with automated morphology analysis offer new tools for characterizing clot development under flow...
  39. pmc Molecular priming of Lyn by GPVI enables an immune receptor to adopt a hemostatic role
    Alec A Schmaier
    Department of Medicine, Division of Cardiology, Division of Hematology, Institute for Medicine and Engineering, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 106:21167-72. 2009
    ....
  40. pmc Determination of surface tissue factor thresholds that trigger coagulation at venous and arterial shear rates: amplification of 100 fM circulating tissue factor requires flow
    Uzoma M Okorie
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, USA
    Blood 111:3507-13. 2008
    ..5-fold increase in fibrin formation under flow. This report defines the threshold concentrations of surface TF required to trigger coagulation under flow...
  41. ncbi request reprint Blood coagulation kinetics: high throughput method for real-time reaction monitoring
    Ken Lo
    Department of Chemical and Biomolecular Engineering, Institute of Medicine and Engineering, University of Pennsylvania, Vagelos Research Laboratories, Philadelphia, PA 19104, USA
    Thromb Haemost 92:874-82. 2004
    ....
  42. pmc Matrix protein microarrays for spatially and compositionally controlled microspot thrombosis under laminar flow
    Uzoma M Okorie
    Department of Chemical and Biomolecular Engineering, Penn Center for Molecular Discovery, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, 19104, USA
    Biophys J 91:3474-81. 2006
    ..Microarrays are ideal for the combinatorial assembly of adhesive and procoagulant proteins to study thrombosis as well as to study axial and lateral transport effects between discrete microspots of distinct composition...
  43. pmc Novel cationic lipids with enhanced gene delivery and antimicrobial activity
    David E Fein
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Pharmacol 78:402-10. 2010
    ..Mixtures of DS and D(2)S can improve transfection activity over common lipofection reagents, and D(2)S has strong antimicrobial action suited for the suppression of bacterial-mediated inflammation...
  44. ncbi request reprint Profiling serine protease substrate specificity with solution phase fluorogenic peptide microarrays
    Dhaval N Gosalia
    Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, PA, USA
    Proteomics 5:1292-8. 2005
    ....
  45. ncbi request reprint Mouse embryonic stem cells efficiently lipofected with nuclear localization peptide result in a high yield of chimeric mice and retain germline transmission potency
    Haiching Ma
    Department of Chemical Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Methods 33:113-20. 2004
    ....
  46. ncbi request reprint Endovascular microcoil gene delivery using immobilized anti-adenovirus antibody for vector tethering
    John M Abrahams
    Department of Neurosurgery, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Stroke 33:1376-82. 2002
    ..Endovascular microcoils are widely used in interventional procedures to treat cerebral aneurysms. In the present study we report for the first time successful use of an endovascular microcoil as a gene delivery system...
  47. ncbi request reprint Platelet-targeting sensor reveals thrombin gradients within blood clots forming in microfluidic assays and in mouse
    J D Welsh
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering Department of Biochemistry and Molecular Biophysics Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    J Thromb Haemost 10:2344-53. 2012
    ..Thrombin undergoes convective and diffusive transport, making it difficult to visualize during thrombosis. We developed the first sensor capable of revealing inner clot thrombin dynamics...
  48. pmc A series of cationic sterol lipids with gene transfer and bactericidal activity
    R A S Randazzo
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
    Bioorg Med Chem 17:3257-65. 2009
    ..Cationic lipids can be optimized for both gene delivery and antibacterial applications by similar modifications...
  49. ncbi request reprint Nonviral gene therapy and its delivery systems
    H Ma
    Institute for Medicine and Engineering, Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104, USA
    Curr Pharm Biotechnol 2:1-17. 2001
    ..This review will concentrate on the current understandings of the basic mechanisms of nonviral gene delivery and new approaches in the field...
  50. ncbi request reprint Delivery of human vascular endothelial growth factor with platinum coils enhances wall thickening and coil impregnation in a rat aneurysm model
    J M Abrahams
    Department of Neurosurgery, Institute for Medicine and Engineering, The Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
    AJNR Am J Neuroradiol 22:1410-7. 2001
    ..This is the first study to hypothesize that rhVEGF may be useful as a surface modification to GDCs for enhancing their therapeutic effects in the treatment of cerebral aneurysms...
  51. pmc Advancing microarray assembly with acoustic dispensing technology
    E Y Wong
    Penn Center for Molecular Discovery, Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Anal Chem 81:509-14. 2009
    ..This platform expands the toolbox for generating analytical arrays and meets needs associated with spatially addressed assembly of multicomponent microarrays on the nanoliter scale...
  52. pmc A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells
    Parag P Shah
    Department of Chemical and Biomolecular Engineering, Penn Center for Molecular Discovery, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6383, USA
    Mol Pharmacol 78:319-24. 2010
    ..Overall, the oxocarbazate CID 23631927 was a subnanomolar, slow-binding, reversible inhibitor of human cathepsin L that blocked SARS-CoV and Ebola pseudotype virus entry in human cells...
  53. ncbi request reprint Fibrin affinity of erythrocyte-coupled tissue-type plasminogen activators endures hemodynamic forces and enhances fibrinolysis in vivo
    Kumkum Ganguly
    Institute for Environmental Medicine, University of Pennsylvania School of Medicine, One John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    J Pharmacol Exp Ther 316:1130-6. 2006
    ..Behavior of RBC/PAs under hemodynamic pressure is an important predictor of their performance in vivo...
  54. pmc Identification and synthesis of a unique thiocarbazate cathepsin L inhibitor
    Michael C Myers
    Penn Center for Molecular Discovery, University of Pennsylvania, 1024 Vagelos Research Laboratories, Philadelphia, PA 19104 6383, USA
    Bioorg Med Chem Lett 18:210-4. 2008
    ..Previously unknown, thiocarbazates (-)-11 and (-)-12 were independently synthesized as single enantiomers and found to inhibit cathepsin L in the low nanomolar range...
  55. pmc A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood
    Keith B Neeves
    1050 Vagelos Laboratories, Department of Chemical and Biomolecular Engineering and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Lab Chip 8:701-9. 2008
    ..We expect this device to be a useful tool in unraveling the role of platelet agonists on clot formation and stability...
  56. pmc Identification and characterization of 3-substituted pyrazolyl esters as alternate substrates for cathepsin B: the confounding effects of DTT and cysteine in biological assays
    Michael C Myers
    Penn Center for Molecular Discovery, University of Pennsylvania, 1024 Vagelos Research Laboratories, Philadelphia, PA 19104 6383, USA
    Bioorg Med Chem Lett 17:4761-6. 2007
    ..Despite the confounding effects of DTT and cysteine, our studies demonstrate that the pyrazole 1 acts as alternate substrate for cathepsin B, rather than as an inhibitor...
  57. ncbi request reprint High throughput substrate specificity profiling of serine and cysteine proteases using solution-phase fluorogenic peptide microarrays
    Dhaval N Gosalia
    Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Proteomics 4:626-36. 2005
    ..Solution-phase microarrays facilitate protease/substrate specificity profiling in a rapid manner with minimal peptide library or enzyme usage...
  58. ncbi request reprint Targeting viral-mediated transduction to the lung airway epithelium with the anti-inflammatory cationic lipid dexamethasone-spermine
    Amber Price
    Department of Bioengineering, Philadelphia, PA 19104, USA
    Mol Ther 12:502-9. 2005
    ..Viral vectors can be formulated with DS/DOPE to improve targeting to the airway epithelium in vivo and to attenuate vector-induced inflammation through the pharmacological activity of DS...
  59. pmc RNA interference screen to identify pathways that enhance or reduce nonviral gene transfer during lipofection
    Gregory A Barker
    Penn Center for Molecular Discovery, Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 16:1602-8. 2008
    ..We have also demonstrated that siRNAs can be co-delivered with lipofected DNA to increase the transfection efficiency in vitro...
  60. pmc Ethanol enhances neutrophil membrane tether growth and slows rolling on P-selectin but reduces capture from flow and firm arrest on IL-1-treated endothelium
    Hana Oh
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Immunol 181:2472-82. 2008
    ..Overall, ethanol caused competing biophysical and biochemical effects that: 1) reduced capture due to PSGL-1 redistribution, 2) reduced rolling velocity due to increased membrane tether growth, and 3) reduced conversion to firm arrest...
  61. ncbi request reprint Adenovirus or HA-2 fusogenic peptide-assisted lipofection increases cytoplasmic levels of plasmid in nondividing endothelium with little enhancement of transgene expression
    Ajit Subramanian
    Institute for Medicine and Engineering, Department of Chemical Engineering, 1024 Vagelos Research Laboratories, Philadelphia, PA 19104, USA
    J Gene Med 4:75-83. 2002
    ..However, there are few studies examining the mechanism and intracellular trafficking of these viral and/or viral fusogenic peptide-assisted lipofections...
  62. ncbi request reprint Microfluidic assay of hemophilic blood clotting: distinct deficits in platelet and fibrin deposition at low factor levels
    T V Colace
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA
    J Thromb Haemost 12:147-58. 2014
    ..Coagulation factor deficiencies create a range of bleeding phenotypes. Microfluidic devices offer controlled hemodynamics and defined procoagulant triggers for measurement of clotting under flow...
  63. ncbi request reprint Pulmonary delivery of adenovirus vector formulated with dexamethasone-spermine facilitates homologous vector re-administration
    A R Price
    Department of Bioengineering, Institute for Medicine and Engineering, Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA
    Gene Ther 14:1594-604. 2007
    ..Transgene-specific T-cell activation was markedly reduced by the DC-Chol/DOPE formulation. Overall, DS/DOPE) facilitated homologous vector re-administration through a combination of liposomal and glucocorticoid mechanisms...
  64. ncbi request reprint Stochastic modeling of blood coagulation initiation
    Ken Lo
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, 19104, USA
    Pathophysiol Haemost Thromb 34:80-90. 2005
    ..6 pl simulations were highly stochastic at this level of TF (50 molecules/16.6 pl). Further experiment and simulation will require evaluation of mechanisms of coagulation kinetics at subpicomolar levels of TF...
  65. pmc Design, synthesis and biological evaluation of a library of thiocarbazates and their activity as cysteine protease inhibitors
    Zhuqing Liu
    Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104 6323, USA
    Comb Chem High Throughput Screen 13:337-51. 2010
    ..This study provides the basis for the design of highly potent and selective inhibitors of the papain family of cysteine proteases...
  66. doi request reprint Hemodynamic regulation of inflammation at the endothelial-neutrophil interface
    Julie Y Ji
    Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratory, 3340 Smith Walk, Philadelphia, PA 19104, USA
    Ann Biomed Eng 36:586-95. 2008
    ..Hemodynamic force exerts anti-inflammatory effects on cytokine-activated endothelium by attenuation of cytokine expression and neutrophil firm arrest...
  67. pmc Membrane cholesterol is a biomechanical regulator of neutrophil adhesion
    Hana Oh
    Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, USA
    Arterioscler Thromb Vasc Biol 29:1290-7. 2009
    ..The purpose of this study was to evaluate the role of membrane cholesterol on human neutrophil and HL-60 biomechanics, capture, rolling, and arrest to P-selectin- or IL-1-activated endothelium...
  68. pmc Cationic lipid formulations alter the in vivo tropism of AAV2/9 vector in lung
    David E Fein
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 17:2078-87. 2009
    ..Our results suggest that formulating AAV2/9 and AAV2/6.2 with DS and D(2)S can lead to improved physicochemical characteristics for in vivo gene delivery to lung...
  69. pmc Disruption of SEMA4D ameliorates platelet hypersensitivity in dyslipidemia and confers protection against the development of atherosclerosis
    Li Zhu
    Department of Medicine and Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 29:1039-45. 2009
    ..Here we tested the hypothesis that deleting sema4D will attenuate the adverse consequences of dyslipidemia on platelets and the vessel wall...
  70. ncbi request reprint Controlled release of DNA/polyamine complex by photoirradiation of a solid phase presenting o-nitrobenzyl ether tethered spermine or polyethyleneimine
    Moon Suk Kim
    Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA
    Bioorg Med Chem Lett 16:5572-5. 2006
    ..The potential exists to employ a DNA-loaded solid phase for spatially, temporally, or dose-controlled release of DNA, at extracellular or intracellular sites...
  71. ncbi request reprint Cationic corticosteroid for nonviral gene delivery
    J A Gruneich
    11024 Vagelos Research Laboratory, Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia 19104, USA
    Gene Ther 11:668-74. 2004
    ..Cationic pharmacophores such as DS represent a new approach to gene delivery and localized therapy...
  72. ncbi request reprint Oligonucleotide-directed single-base DNA alterations in mouse embryonic stem cells
    E A Pierce
    FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Gene Ther 10:24-33. 2003
    ..The targeted ES cells could in turn be used to create accurate mouse models of inherited diseases...
  73. pmc Printing chemical libraries on microarrays for fluid phase nanoliter reactions
    Dhaval N Gosalia
    Institute for Medicine and Engineering, Department of Bioengineering, University of Pennsylvania, 1024 Vagelos Research Laboratory, 3340 Smith Walk, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 100:8721-6. 2003
    ..From one printing run that consumes <1 nanomole of each compound, large combinatorial libraries can be subjected to numerous separation-free homogeneous assays at volumes 103-104 smaller than current high-throughput methods...
  74. pmc Identification of triazinoindol-benzimidazolones as nanomolar inhibitors of the Mycobacterium tuberculosis enzyme TDP-6-deoxy-d-xylo-4-hexopyranosid-4-ulose 3,5-epimerase (RmlC)
    Sharmila Sivendran
    Penn Center for Molecular Discovery, Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratories, University of Pennsylvania, Philadelphia, PA 19104, USA
    Bioorg Med Chem 18:896-908. 2010
    ..Computer modeling showed that the binding of the tethered two-ringed system into the active site occurred at the thymidine binding region for one ring system and the sugar region for the other ring system...
  75. pmc Discovery of potent small-molecule inhibitors of multidrug-resistant Plasmodium falciparum using a novel miniaturized high-throughput luciferase-based assay
    Edinson Lucumi
    Department of Chemical and Biomolecular Engineering and Penn Center for Molecular Discovery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Antimicrob Agents Chemother 54:3597-604. 2010
    ..Ultimately, this study may provide new probes to understand the molecular details of the malaria life cycle and to identify new antimalarials...
  76. pmc Lattice kinetic Monte Carlo simulations of convective-diffusive systems
    Matthew H Flamm
    Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Chem Phys 130:094904. 2009
    ..This is the first generally applicable lattice kinetic Monte Carlo simulation for convection-diffusion and will allow simulations of field-driven phenomena in which drift is present in addition to diffusion...
  77. ncbi request reprint Functional phenotyping of human plasma using a 361-fluorogenic substrate biosensing microarray
    Dhaval N Gosalia
    Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104 6281, USA
    Biotechnol Bioeng 94:1099-110. 2006
    ..This method may allow development of future biosensors using minimal and non-specific markers. These substrates can be applied to real-time diagnostic biosensing of complex protease mixtures...
  78. pmc Evaluation of an orthogonal pooling strategy for rapid high-throughput screening of proteases
    Nuzhat Motlekar
    Penn Center for Molecular Discovery, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Assay Drug Dev Technol 6:395-405. 2008
    ..Based on these results the orthogonal pooling strategy has been used successfully to rapidly screen several cysteine and serine proteases...
  79. pmc A molecular signaling model of platelet phosphoinositide and calcium regulation during homeostasis and P2Y1 activation
    Jeremy E Purvis
    Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, USA
    Blood 112:4069-79. 2008
    ..This integrative approach to platelet biology offers a novel and complementary strategy to traditional reductionist methods...
  80. pmc Comparison of PSGL-1 microbead and neutrophil rolling: microvillus elongation stabilizes P-selectin bond clusters
    Eric Y H Park
    Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, USA
    Biophys J 82:1835-47. 2002
    ..Our results suggest that microvillus extension during transient PSGL-1/P-selectin bonding may enhance the robustness of neutrophil rolling interactions...
  81. pmc Selectin-like kinetics and biomechanics promote rapid platelet adhesion in flow: the GPIb(alpha)-vWF tether bond
    Teresa A Doggett
    Division of Newborn Medicine, Department of Pediatrics, Washington University and St Louis Children s Hospital, St Louis, Missouri 63110, USA
    Biophys J 83:194-205. 2002
    ....
  82. ncbi request reprint Alterations in the intrinsic properties of the GPIbalpha-VWF tether bond define the kinetics of the platelet-type von Willebrand disease mutation, Gly233Val
    Teresa A Doggett
    Division of Newborn Medicine, Department of Pediatrics, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8208, St Louis, MO 93110, USA
    Blood 102:152-60. 2003
    ....
  83. ncbi request reprint A Saccharomyces cerevisiae cell-based quantitative beta-galactosidase assay compatible with robotic handling and high-throughput screening
    Rogerio Alves de Almeida
    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK
    Yeast 25:71-6. 2008
    ..The high-sensitivity, miniaturized format reduced sample handling required will make this assay useful for a wide range of applications...
  84. ncbi request reprint Nanoliter homogenous ultra-high throughput screening microarray for lead discoveries and IC50 profiling
    Haiching Ma
    Reaction Biology Corporation, Malvern, PA 19355, USA
    Assay Drug Dev Technol 3:177-87. 2005
    ....
  85. ncbi request reprint Microarrays for the functional analysis of the chemical-kinase interactome
    Kurumi Y Horiuchi
    Reaction Biology Corporation, Malvern, PA 19355, USA
    J Biomol Screen 11:48-56. 2006
    ..All results indicate that this platform is well suited for kinetic analysis, HTS, large-scale IC50 determinations, and selectivity profiling...

Research Grants26

  1. Blood Systems Biology
    Scott L Diamond; Fiscal Year: 2010
    ..Clotting and bleeding diseases of aging are seldom due to acquired mutations and this drives the need for advanced functional phenotyping in concert with Systems Biology and other sequencing/genomic approaches. ..
  2. Multiplexed HTS of Serine and Cysteine Proteases (RMI)
    Scott Diamond; Fiscal Year: 2005
    ..The use of multiplexed assay on microarrays allows the generation of critical data for the chemical protease interactome. ..
  3. Mechanisms of Cardiopulmonary Gene Transfer
    Scott Diamond; Fiscal Year: 2006
    ..Overall, these bioengineering studies will focus on barriers/rate limits that prevent high efficiency gene transfer. ..
  4. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2007
    ..Overall, these studies seek to provide fundamental insight into cell-cell interacitions and coagulation biochemistry that occur under flow. ..
  5. Blood Systems Biology
    Scott Diamond; Fiscal Year: 2007
    ....
  6. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2009
    ..Overall, these studies seek to provide fundamental insight into cell-cell interacitions and coagulation biochemistry that occur under flow. ..
  7. Mechanisms of Cardiopulmonary Gene Transfer
    Scott L Diamond; Fiscal Year: 2010
    ..Novel cationic steroid delivery molecules will be tested for improved targeting and for allowing readministration of virus vector to eliminate the need for biomanufacturing of multiple serotypes. ..
  8. Mechanisms of Cardiopulmonary Gene Transfer
    Scott Diamond; Fiscal Year: 2005
    ..Overall, these bioengineering studies will focus on barriers/rate limits that prevent high efficiency gene transfer. ..
  9. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2005
    ..Overall, these studies seek to provide fundamental insight into cell-cell interacitions and coagulation biochemistry that occur under flow. ..
  10. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2004
    ..Overall, these studies seek to provide fundamental insight into cell-cell interactions and coagulation biochemistry that occur under flow. ..
  11. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2001
    ..Overall, these studies seek to provide fundamental insight into cell-cell interactions and coagulation biochemistry that occur under flow. ..
  12. MECHANISMS OF NONVIRAL CARDIOVASCULAR GENE TRANSFER
    Scott Diamond; Fiscal Year: 2003
    ..Overall, these studies will investigate the delivery of plasmids to the nucleus of nondividing endothelium or smooth muscle cells in order to improve nonviral gene transfer. ..
  13. REACTION AND TRANSPORT DYNAMICS DURING THROMBOLYSIS
    Scott Diamond; Fiscal Year: 1999
    ..Overall, the understanding of spatial dynamics in dissolving thrombi will help facilitate the rational design and optimization of lytic therapy, particularly those approaches involving catheters or combined therapeutic agents. ..
  14. MECHANISMS OF NONVIRAL CARDIOVASCULAR GENE TRANSFER
    Scott Diamond; Fiscal Year: 2001
    ..Overall, these studies will investigate the delivery of plasmids to the nucleus of nondividing endothelium or smooth muscle cells in order to improve nonviral gene transfer. ..
  15. MECHANISMS OF NONVIRAL CARDIOVASCULAR GENE TRANSFER
    Scott Diamond; Fiscal Year: 2002
    ..Overall, these studies will investigate the delivery of plasmids to the nucleus of nondividing endothelium or smooth muscle cells in order to improve nonviral gene transfer. ..
  16. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2002
    ..Overall, these studies seek to provide fundamental insight into cell-cell interactions and coagulation biochemistry that occur under flow. ..
  17. Mechanisms of Cardiopulmonary Gene Transfer
    Scott Diamond; Fiscal Year: 2007
    ..Overall, these bioengineering studies will focus on barriers/rate limits that prevent high efficiency gene transfer. ..
  18. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2003
    ..Overall, these studies seek to provide fundamental insight into cell-cell interactions and coagulation biochemistry that occur under flow. ..
  19. MECHANISMS OF NONVIRAL CARDIOVASCULAR GENE TRANSFER
    Scott Diamond; Fiscal Year: 2004
    ..Overall, these studies will investigate the delivery of plasmids to the nucleus of nondividing endothelium or smooth muscle cells in order to improve nonviral gene transfer. ..
  20. Reaction and Transport Dynamics in Human Blood
    Scott Diamond; Fiscal Year: 2006
    ..Overall, these studies seek to provide fundamental insight into cell-cell interacitions and coagulation biochemistry that occur under flow. ..