Research Topics
Genomes and Genes | S L DiamondSummaryAffiliation: University of Pennsylvania Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradientRyan W Muthard
Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104
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...
Direct observation of von Willebrand factor elongation and fiber formation on collagen during acute whole blood exposure to pathological flowThomas 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...- Blood clots are rapidly assembled hemodynamic sensors: flow arrest triggers intraluminal thrombus contractionRyan 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... - Thrombus growth and embolism on tissue factor-bearing collagen surfaces under flow: role of thrombin with and without fibrinThomas 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... - Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juiceKatarzyna 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... 
Methods for mapping protease specificityScott 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...- Proteases' prime targets revealedScott L Diamond
Department of Chemical Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratories, Philadelphia, Pennsylvania 19104-6383, USA
Nat Biotechnol 26:652-3. 2008 - Tissue factor activity under flowScott 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... - Systems biology to predict blood functionS 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... - Harry L. Goldsmith, Ph.dScott L Diamond
University of Pennsylvania, Philadelphia, PA, USA
Ann Biomed Eng 36:523-6. 2008 - Engineering design of optimal strategies for blood clot dissolutionS 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... - Biodegradable polyglycolide endovascular coils promote wall thickening and drug delivery in a rat aneurysm modelJ 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... - Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin LParag 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... - Thrombin flux and wall shear rate regulate fibrin fiber deposition state during polymerization under flowK 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... - Shear stress causes nuclear localization of endothelial glucocorticoid receptor and expression from the GRE promoterJulie Y Ji
Institute for Medicine and Engineering, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
Circ Res 92:279-85. 2003.... - Neutrophil enhancement of fibrin deposition under flow through platelet-dependent and -independent mechanismsM 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... - Design, synthesis, and evaluation of inhibitors of cathepsin L: Exploiting a unique thiocarbazate chemotypeMichael 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... - Neutrophil-bead collision assay: pharmacologically induced changes in membrane mechanics regulate the PSGL-1/P-selectin adhesion lifetimeK 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... - Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear-resistance of platelet aggregatesK 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... - Interplay between membrane cholesterol and ethanol differentially regulates neutrophil tether mechanics and rolling dynamicsM 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... - Adhesion of normal erythrocytes at depressed venous shear rates to activated neutrophils, activated platelets, and fibrin polymerized from plasmaMukul 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... - Neutrophil cathepsin G promotes prothrombinase and fibrin formation under flow conditions by activating fibrinogen-adherent plateletsMukul 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... - Multiscale systems biology and physics of thrombosis under flowMathew 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... - Endothelial cell specific adhesion molecule (ESAM) localizes to platelet-platelet contacts and regulates thrombus formation in vivoT 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... - P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditionsS 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... - Factor VIIa-mediated tenase function on activated platelets under flowM 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... - Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagentsJeffrey 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.... - Surfactants attenuate gas embolism-induced thrombin productionDavid 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... - Combined antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugateRobert 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... - Molecular docking of cathepsin L inhibitors in the binding site of papainMary 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.... - High-throughput screening for modulators of mesenchymal stem cell chondrogenesisALICE 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... - Exogenous nitric oxide activates the endothelial glucocorticoid receptorJulie 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... - Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entryGraham 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... - Analysis of morphology of platelet aggregates formed on collagen under laminar blood flowT 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... - Novel cationic lipids with enhanced gene delivery and antimicrobial activityDavid 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... - Molecular priming of Lyn by GPVI enables an immune receptor to adopt a hemostatic roleAlec 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.... - Blood coagulation kinetics: high throughput method for real-time reaction monitoringKen 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.... - Determination of surface tissue factor thresholds that trigger coagulation at venous and arterial shear rates: amplification of 100 fM circulating tissue factor requires flowUzoma 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... - Profiling serine protease substrate specificity with solution phase fluorogenic peptide microarraysDhaval N Gosalia
Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, PA, USA
Proteomics 5:1292-8. 2005.... - Endovascular microcoil gene delivery using immobilized anti-adenovirus antibody for vector tetheringJohn M Abrahams
Department of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
Stroke 33:1376-82. 2002.... - Mouse embryonic stem cells efficiently lipofected with nuclear localization peptide result in a high yield of chimeric mice and retain germline transmission potencyHaiching Ma
Department of Chemical Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
Methods 33:113-20. 2004.... - Matrix protein microarrays for spatially and compositionally controlled microspot thrombosis under laminar flowUzoma 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... - A series of cationic sterol lipids with gene transfer and bactericidal activityR 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... - Nonviral gene therapy and its delivery systemsH 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... - Delivery of human vascular endothelial growth factor with platinum coils enhances wall thickening and coil impregnation in a rat aneurysm modelJ 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... - Advancing microarray assembly with acoustic dispensing technologyE 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... - High throughput substrate specificity profiling of serine and cysteine proteases using solution-phase fluorogenic peptide microarraysDhaval 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... - Targeting viral-mediated transduction to the lung airway epithelium with the anti-inflammatory cationic lipid dexamethasone-spermineAmber 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... - Fibrin affinity of erythrocyte-coupled tissue-type plasminogen activators endures hemodynamic forces and enhances fibrinolysis in vivoKumkum 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... - A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cellsParag 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... - RNA interference screen to identify pathways that enhance or reduce nonviral gene transfer during lipofectionGregory 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... - Identification and characterization of 3-substituted pyrazolyl esters as alternate substrates for cathepsin B: the confounding effects of DTT and cysteine in biological assaysMichael 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... - Adenovirus or HA-2 fusogenic peptide-assisted lipofection increases cytoplasmic levels of plasmid in nondividing endothelium with little enhancement of transgene expressionAjit 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..CONCLUSION: These results indicate that enhancement of endosome escape in nondividing cells does not fully alleviate rate limits related to nuclear import of the plasmid... - A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing bloodKeith 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... - Ethanol enhances neutrophil membrane tether growth and slows rolling on P-selectin but reduces capture from flow and firm arrest on IL-1-treated endotheliumHana 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... - Identification and synthesis of a unique thiocarbazate cathepsin L inhibitorMichael 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... - Pulmonary delivery of adenovirus vector formulated with dexamethasone-spermine facilitates homologous vector re-administrationA 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... - Pairwise agonist scanning predicts cellular signaling responses to combinatorial stimuliManash 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... - Hemodynamic regulation of inflammation at the endothelial-neutrophil interfaceJulie 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... - Design, synthesis and biological evaluation of a library of thiocarbazates and their activity as cysteine protease inhibitorsZhuqing 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... - Stochastic modeling of blood coagulation initiationKen 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... - Controlled release of DNA/polyamine complex by photoirradiation of a solid phase presenting o-nitrobenzyl ether tethered spermine or polyethyleneimineMoon 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... - Cationic lipid formulations alter the in vivo tropism of AAV2/9 vector in lungDavid 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... - Disruption of SEMA4D ameliorates platelet hypersensitivity in dyslipidemia and confers protection against the development of atherosclerosisLi 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... - Membrane cholesterol is a biomechanical regulator of neutrophil adhesionHana 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... - Oligonucleotide-directed single-base DNA alterations in mouse embryonic stem cellsE 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... - Cationic corticosteroid for nonviral gene deliveryJ 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... - Lattice kinetic Monte Carlo simulations of convective-diffusive systemsMatthew 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... - Evaluation of an orthogonal pooling strategy for rapid high-throughput screening of proteasesNuzhat 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... - A molecular signaling model of platelet phosphoinositide and calcium regulation during homeostasis and P2Y1 activationJeremy 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... - Discovery of potent small-molecule inhibitors of multidrug-resistant Plasmodium falciparum using a novel miniaturized high-throughput luciferase-based assayEdinson 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... - Functional phenotyping of human plasma using a 361-fluorogenic substrate biosensing microarrayDhaval 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... - Printing chemical libraries on microarrays for fluid phase nanoliter reactionsDhaval 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... - 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... - Steady-state kinetic modeling constrains cellular resting states and dynamic behaviorJeremy 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... - Comparison of PSGL-1 microbead and neutrophil rolling: microvillus elongation stabilizes P-selectin bond clustersEric 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... - Alterations in the intrinsic properties of the GPIbalpha-VWF tether bond define the kinetics of the platelet-type von Willebrand disease mutation, Gly233ValTeresa 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.... - Selectin-like kinetics and biomechanics promote rapid platelet adhesion in flow: the GPIb(alpha)-vWF tether bondTeresa 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.... - Microarrays for the functional analysis of the chemical-kinase interactomeKurumi 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... - A Saccharomyces cerevisiae cell-based quantitative beta-galactosidase assay compatible with robotic handling and high-throughput screeningRogerio 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... - Nanoliter homogenous ultra-high throughput screening microarray for lead discoveries and IC50 profilingHaiching Ma
Reaction Biology Corporation, Malvern, PA 19355, USA
Assay Drug Dev Technol 3:177-87. 2005....
Research Grants
- Blood Systems BiologyScott 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. ..
- Mechanisms of Cardiopulmonary Gene TransferScott Diamond; Fiscal Year: 2007..Overall, these bioengineering studies will focus on barriers/rate limits that prevent high efficiency gene transfer. ..
- Blood Systems BiologyScott Diamond; Fiscal Year: 2007....
- Reaction and Transport Dynamics in Human BloodScott Diamond; Fiscal Year: 2009..Overall, these studies seek to provide fundamental insight into cell-cell interacitions and coagulation biochemistry that occur under flow. ..
- Mechanisms of Cardiopulmonary Gene TransferScott 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. ..
- 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. ..
- REACTION AND TRANSPORT DYNAMICS DURING THROMBOLYSISScott 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. ..
- MECHANISMS OF NONVIRAL CARDIOVASCULAR GENE TRANSFERScott 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. ..
- Reaction and Transport Dynamics in Human BloodScott Diamond; Fiscal Year: 2004..Overall, these studies seek to provide fundamental insight into cell-cell interactions and coagulation biochemistry that occur under flow. ..