SEAS Standing Faculty Research Directory
by Department
Bioengineering
Chemical and Biomolecular Engineering
Computer and Information Science
Electrical and Systems Engineering
Mechanical Engineering and Applied Mechanics
Materials Science and Engineering
Bioengineering
Daniel K. Bogen
Associate Professor of Bioengineering; Associate Professor of Bioengineering in Medicine; Associate Professor of Rehabilitation Medicine; Associate Professor of Bioengineering in Pediatrics
Email: dan at seas.upenn.edu
Personal Website
Research Interests: My primary research interest is in pediatric rehabilitation engineering-developing new technology to diagnose and treat disabled children. I am especially interested in cognitive rehabilitation of children with brain injury and other neurological or cognitive disorders. This work involves the development of new kinds of pediatric user-interfaces to biomedical devices-interfaces which are appealing to children, and which allow the children to operate diagnostic and therapeutic instruments.
Selected Recent Publications: S. K. Lin, S. T. Kuna and D. K. Bogen, "A novel device for measuring long-term oxygen therapy adherence: a preliminary validation," Respir.Care 51 (3), 266-271 (2006).
T. D. Yoo et al., "Geometric and biomechanical analysis for computer-aided design of assistive medical devices," Comput.-Aided Des. 37 (14), 1521-1532 (2005).
D. Bogen and A. J. Apter, "Adherence logger for a dry powder inhaler: a new device for medical adherence research," J.Allergy Clin.Immunol. 114 (4), 863-868 (2004).
T. D. Yoo et al., "Geometrical analysis for assistive medical device design," Computational and Information Science, Proceedings 3314, 916-921 (2004).
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Gershon Buchsbaum
Professor of Bioengineering; Member of the Institute for Neurological Sciences; Member of the Institute for Medicine and Engineering; Member of the Institute for Research in the Cognitive Sciences
Email: gershon at seas.upenn.edu
Personal Website | Research Website
Research Interests: Visual signal processing and image coding, modeling of retinal and visual system architecture and function, auditory-visual scene analysis, computational neuroscience. Research Techniques: Modeling and simulation; image processing; digital signal processing; neural networks. Research Summary: The neural architecture of the visual system with its unique and elaborate response properties in space, time and color provides us with all the features and richness of our visual world. The main goals of our research are: 1) to understand how the visual neural architecture is matched to the image and how it samples, codes and processes the different features of the image. 2) To identify the attributes of natural images that are most critical for coding in the visual system. Questions we ask are: What are the significant correlations and functional relations among the different image features? How do critical parameters such as contrast in time, space and color and local and global details affect visual image processing? How does visual processing match and adapt to dynamic changes in the image? How does the visual system extract image features such as spatial detail and color? To investigate these questions, we apply quantitative analysis and simulation methods from image processing and neural networks that are rigorously based on known anatomy and physiology and explore the design principles and strategy underlying the visual system neural architecture.
Selected Recent Publications: G. Buchsbaum and O. Bloch, "Color categories revealed by non-negative matrix factorization of Munsell color spectra," Vision Res. 42 (5), 559-563 (2002).
A. Hsu et al., "Cost of cone coupling to trichromacy in primate fovea," J.Opt.Soc.Am.A Opt.Image Sci.Vis. 17 (3), 635-640 (2000).
R. Rao-Mirotznik, G. Buchsbaum and P. Sterling, "Transmitter concentration at a three-dimensional synapse," J.Neurophysiol. 80 (6), 3163-3172 (1998).
B. Levitan and G. Buchsbaum, "Parallel cone bipolar to on-beta ganglion cell pathways in the cat retina: spatial responses, spatial aliasing, and spatial variance," J.Opt.Soc.Am.A Opt.Image Sci.Vis. 13 (6), 1152-1165 (1996).
S. M. Courtney, L. H. Finkel and G. Buchsbaum, "Network simulations of retinal and cortical contributions to color constancy," Vision Res. 35 (3), 413-434 (1995).
S. M. Courtney, L. H. Finkel and G. Buchsbaum, "Network simulations of retinal and cortical contributions to color constancy," Vision Res. 35 (3), 413-434 (1995).
C. K. Kier, G. Buchsbaum and P. Sterling, "How retinal microcircuits scale for ganglion cells of different size," J.Neurosci. 15 (11), 7673-7683 (1995).
R. Rao-Mirotznik et al., "Mammalian rod terminal: architecture of a binary synapse," Neuron 14 (3), 561-569 (1995).
R. Rao, G. Buchsbaum and P. Sterling, "Rate of quantal transmitter release at the mammalian rod synapse," Biophys.J. 67 (1), 57-63 (1994).
M. P. Eckert and G. Buchsbaum, "Efficient coding of natural time varying images in the early visual system," Philos.Trans.R.Soc.Lond.B.Biol.Sci. 339 (1290), 385-395 (1993).
B. Levitan and G. Buchsbaum, "Signal sampling and propagation through multiple cell layers in the retina: modeling and analysis with multirate filtering," J.Opt.Soc.Am.A 10 (7), 1463-1480 (1993).
B. Lee, M. Litt and G. Buchsbaum, "Rheology of the vitreous body. Part I: Viscoelasticity of human vitreous," Biorheology 29 (5-6), 521-533 (1992).
S. M. Courtney and G. Buchsbaum, "Temporal differences between color pathways within the retina as a possible origin of subjective colors," Vision Res. 31 (9), 1541-1548 (1991).
A. M. Rohaly and G. Buchsbaum, "Global spatiochromatic mechanism accounting for luminance variations in contrast sensitivity functions," J.Opt.Soc.Am.A 6 (2), 312-317 (1989).
A. M. Rohaly and G. Buchsbaum, "Inference of global spatiochromatic mechanisms from contrast sensitivity functions," J.Opt.Soc.Am.A 5 (4), 572-576 (1988).
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Jason A. Burdick
Assistant Professor of Bioengineering
Email: burdick2 at seas.upenn.edu
Personal Website | Research Website
Research Interests: Developing degradable polymeric biomaterials that can be used for tissue engineering, drug delivery, and fundamental polymer studies. The platform polymer technology involves the development of multifunctional monomers that form degradable crosslinked networks via a radical polymerization. Dr. Burdick's specific research interests include: scaffolding for cell and growth factor delivery in bone and cartilage regeneration, controlling stem cell differentiation, growth factor delivery, and investigating the influence of monomer structure on resulting network macroscopic and microscopic properties.
Selected Recent Publications: A.R. Tan, B.M. Baker, J.L. Ifkovits, D.M. Brey, R.L.Mauck, J.A. Burdick, “Electrospinning of Photocrosslinked and Degradable Fibrous Scaffolds,” in preparation.
C. Chung and J.A. Burdick, “Engineering Cartilage Tissue,” Advanced Drug Delivery Reviews, in preparation (invited review).
J.S. Katz and J.A. Burdick, “Hydrogel Mediated Delivery of Trophic Factors for Neural Repair,” Wiley Interdisciplinary Reviews – Nanomedicine, submitted.
P.M. George, R. Saigal, M. Lawlor, M.J. Moore, D.A. LaVan, R. Marini, M. Selig, M. Makhni, J.A. Burdick, R. Langer, D.S. Kohane, “Stand-Alone Three-Dimensional Conductive Constructs for Nerve Regeneration and Other Applications,” submitted.
J.L. Ifkovits and J.A. Burdick, “Photopolymerizable and Degradable Biomaterials for Tissue Engineering Applications,” Tissue Engineering, in press.
D.M. Brey, I. Erickson, and J.A. Burdick, “Influence of Macromer Molecular Weight and Chemistry on Poly(b-amino ester) Network Properties and Initial Cell Interactions,” Journal of Biomedical Materials Research A, in press.
S. Gerecht, J.A. Burdick, L.S. Ferreira, S.A. Townsend, R. Langer, G. Vunjak-Novakovic, “Hyaluronic Acid Hydrogel for Controlled Self-renewal and Differentiation of Human Embryonic Stem Cells,” Proceedings of the National Academy of Sciences (PNAS), 104:11298-11303, 2007.
E. Figallo, C. Cannizzaro, S. Gerecht, J.A. Burdick, R. Langer, N. Elvassore, G. Vunjak-Novakovic, “Micro Bioreactor Array for Controlling Cellular Microenvironments,” Lab on a Chip, 7:710-719, 2007.
S. Gerecht, J.A. Burdick, C. Cannizzaro, G. Vunjak-Novakovic, “3D Cultivation of Human Embryonic Stem Cells,” in Human Embryonic Stem Cells (eds. J. Masters, B. Palsson, J. Thomson), Springer Verlag, 2007.
Y. Yeo, W. Geng, T. Ito, D.S. Kohane, J.A. Burdick, M. Radisic, “Photocrosslinkable Hydrogel for Myocyte Cell Culture and Injection,” Journal of Biomedical Materials Research B, Applied Biomaterials, 81B:312-322, 2007.
A. Khademhosseini, G. Eng, J. Yeh, J. Fukuda, J. Blumling, R. Langer, J.A. Burdick, “Micromolding of Photocrosslinkable Hyaluronic Acid for Cell Encapsulation and Entrapment,” Journal of Biomedical Materials Research A, 79A:522-532, 2006.
D.G. Anderson, C.A. Tweedie, N. Hossain, S.M. Navarro, D.M. Brey, K.J. Van Vliet, R. Langer, J.A. Burdick, “A Combinatorial Library of Photocrosslinkable and Degradable Materials,” Advanced Materials, 18:2614-2618, 2006.
J.A. Burdick*, J. Piantino*, D. Goldberg, R. Langer, L.I. Benowitz, “An Injectable, Degradable Hydrogel for Trophic Factor Delivery Enhances Axonal Rewiring and Improves Performance after Spinal Cord Injury,” Experimental Neurology, 201: 359-367, 2006.
C. Chung, J. Mesa, G.J. Miller, M.A. Randolph, T. Gill, J.A. Burdick, “Effects of Auricular Chondrocyte Expansion on Neocartilage Formation in Photocrosslinkable Hyaluronic Acid Networks,” Tissue Engineering, 12:2665-2673, 2006.
C. Chung, J. Mesa, M.A. Randolph, M. Yaremchuk, J.A. Burdick, “Influence of Gel Properties on Neocartilage Formation by Auricular Chondrocytes Photoencapsulated in Hyaluronic Acid Networks,” Journal of Biomedical Materials Research A, 77A: 518-525, 2006.
Y. Yeo, J.A. Burdick, C.B. Highley, R. Marini, R. Langer, D.S. Kohane, “Peritoneal Application of Chitosan and UV-crosslinkable Chitosan,” Journal of Biomedical Materials Research A, 78A: 668-675, 2006.
P.M. George, D.A. LaVan, J.A. Burdick, C.Y. Chen, E. Liang, R. Langer, “Electrically Controlled Drug Delivery from a Biotin-Doped Conductive Polypyrrole,” Advanced Materials, 18: 577-581, 2006.
J.A. Burdick, M. Ward, E. Liang, M.J. Young, R. Langer, “Stimulation of Neurite Outgrowth by Neurotrophins Delivered from Degradable Hydrogels,” Biomaterials, 27: 452-459, 2006.
J.A. Burdick and Molly M. Stevens, “Biomedical Hydrogels,” in Biomaterials, Artificial Organs, and Tissue Engineering (eds. J. Jones and L. Hench), Woodhead Publishing Ltd., Cambridge, 2005.
B.A. Pfeifer, J.A. Burdick, S. Little, R. Langer, “Poly(ester-anhydride):Poly(b-amino ester) Micro- and Nanospheres: DNA Encapsulation and Cellular Transfection,” International Journal of Pharmaceutics, 304, 210-219, 2005.
J.A. Burdick*, S. Levenberg*, T. Kraehenbuehl, R. Langer, “Neurotrophin Induced Differentiation of Human Embryonic Stem Cells on 3-Dimensional Polymeric Scaffolds,” Tissue Engineering, 11: 506-512, 2005. (*authors contributed equally)
J.A. Burdick, C. Chung, X. Jia, M.A. Randolph, R. Langer, “Controlled Degradation and Mechanical Behavior of Photopolymerized Hyaluronic Acid Networks,” Biomacromolecules, 6: 386-391, 2005.
B.A. Pfeifer, J.A. Burdick, R. Langer, “Formulation and Surface Modification of Poly(Ester-Anhydride) Micro- and Nanospheres,” Biomaterials, 26: 117-124, 2005.
T.M. Lovestead, J.A. Burdick, K.S. Anseth, C.N. Bowman, “Understanding Multivinyl Monomer Photopolymerization Kinetics through Modeling and GPC Investigation of Degradable Networks,” Polymer, 46: 6226-6234, 2005.
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Christopher S. Chen
Associate Professor of Bioengineering
Email: chrischen at seas.upenn.edu
Personal Website | Research Website
Research Interests: Micro- and Nanotechnology; Transduction of mechanical forces by cells; Relationship between cellular and multicellular structure and biological function; Angiogenesis; Cancer; and Stem cell biology. Dr. Chen's laboratory studies how the interactions between cells and their surrounding tissue microenvironment drives their behavior. His group develops novel microfabriaction and nanotechnology-based tools to manipulate and monitor these interactions in order to better understand how cells function in normal and disease contexts.
Selected Recent Publications: Bhatia, S.N, Chen, C.S. (2007) Special issue on Cell and Tissue Engineering in Microsystems. Lab on a Chip. 7: 666.
Nelson, C.M., Liu, W.F., Chen, C.S. (2007) Manipulation of Cell-Cell Adhesion Using Bowtie-Shaped Microwells. In Methods in Molecular Biology: Adhesion Protein Protocols, 2nd Ed. (ed. A.S. Coutts). Human Press. 270: 1-9.
Alom Ruiz, S., Chen, C.S. (2007) Microcontact printing: a tool to pattern. Soft Matter. 3(2):168-177.
Pirone, D.M., Liu, W.F., Gao, L., Raghavan, S., Lemmon, C.A., Romer, L.H., Chen, C.S. (2006) An Inhibitory Role for FAK in Regulating Proliferation: a Link Between Limited Adhesion and RhoA-ROCK Signaling. J Cell Biol. 174(2):277-88.
Liu, W.F., Nelson, C.M., Pirone, D.M., Chen, C.S. (2006) E-cadherin Engagement Stimulates Proliferation Via Rac1. J Cell Biol. 173(3):431-441.
Sniadecki, N.J., Desai, R.D., Alom Ruiz, S., Chen, C.S. (2006) Nanotechnology for Cell-Substrate Interactions. Annals of Biomed Eng. 34(1):59-74.
Jean, R., Spector, A., Chen, C.S. (2005) Finite-element analysis of the adhesion-cytoskeleton-nucleus mechanotransduction pathway during endothelial cell rounding: axisymmetric model. J Biomech Eng. 127(4):594-600.
Nelson, C.M., Jean, R.P., Tan, J.L., Liu, W.F., Sniadecki, N.J., Spector, A.A., Chen, C.S., (2005) Emergent patterns of growth contolled by multicellular form and mechanics. Proc Nat Acad Sci. 102(33):11594-11599.
Herndon, T.M., Pirone, D.M., Tsokos, G.C., Chen, C.S., (2005) T cell-to-T cell clustering enhances NF-κB activitity by a PI3K signal mediated by Cbl-b and Rho. Biochem Biophys Res Comm. 332:1133-1139.
Tanase, M., Felton, E.J., Gray, D.S., Hultgren, A., Chen, C.S., Reich, D. (2005) Assembly of multicellular constructs and microarrays of cells using magnetic nanowires. Lab on a Chip. 5:598-605.
Lemmon, C.A., Sniadecki, N.J., Ruiz, S.A., Tan, J.T., Romer, L.H., Chen, C.S. (2005) Shear Force at the Cell-Matrix Interface: Enhanced Analysis For Microfabricated Post Array Detectors. Mechanics & Chemistry of Biosystems. 2(1):1-16.
Yim, E.K.F., Reano, R.M., Pang, S.W., Yee, A.F., Chen, C.S., Leong, K.W. (2005) Nanopattern-induced changes in morphology and motility in smooth muscle cells. Biomaterials. 26:54035-5413.
Chen, C.S., Jiang, X., Whitesides, G.M. (2005) Microengineering the Enviroment of Mammalian Cells in Culture. MRS Bulletin. 30:194-201.
Wang, A.Y., Mo, X., Chen, C.S., Yu, S.M., (2005) Facile Modification of Collagen Directed by Collagen Mimetic Peptides. J Am Chem Soc. 127(12):4130-4131
Hultgren, A., Tanase, M., Felton, E.J., Bhadriraju, K., Salem, A.K., Chen, C.S., Reich, D. (2005) Optimization of Yield in Magnetic Cell Separations Using Nickel Nanowires of Different Lengths. Biotech Prog. 21:509-515.
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Paul Ducheyne
Professor of Bioengineering; Professor of Orthopaedic Surgery Research; Member of the Institute for Medicine and Engineering; Director of Center for Bioactive Materials and Tissue Engineering
Email: ducheyne at seas.upenn.edu
Personal Website | Research Website
Research Interests: Since the late 1980's when the challenge of in vitro synthesis of bone tissue was first addressed, the investigation of mechanistic effects of materials on cellular functions, specifically cell attachment, proliferation, differentiation and extracellular matrix formation, have been central to this lab's activities. Analyses deal extensively with the interface zone between materials and cells and tissues, using both materials science techniques as well as life science methods. In addition, studies focus on the combined effects of microgravity and substrate material on cellular functions; the use of self assembled monolayer chemistry to create highly controlled surfaces; studying the effect of calcification of such surfaces on cell function; and the controlled release of growth factors, cytokines, antibiotics, etc.... from bioactive, silica based sol gels.
Selected Recent Publications: M. H. Lee et al., "Adhesion of MC3T3-E1 cells to RGD peptides of different flanking residues: Detachment strength and correlation with long-term cellular function," Journal of Biomedical Materials Research Part a 81A (1), 150-160 (2007).
S. Radin and P. Ducheyne, "Controlled release of vancomycin from thin sol-gel films on titanium alloy fracture plate material," Biomaterials 28 (9), 1721-1729 (2007).
A. G. Secchi et al., "RGDS peptides immobilized on titanium alloy stimulate bone cell attachment, differentiation and confer resistance to apoptosis," J.Biomed.Mater.Res.A. , (2007).
G. A. Silva et al., "The effect of starch and starch-bioactive glass composite microparticles on the adhesion and expression of the osteoblastic phenotype of a bone cell line," Biomaterials 28 (2), 326-334 (2007).
V. Antoci et al., "Antibiotic integral to implant surface inhibits bacterial, but not osteoblast colonization." Journal of Bone and Mineral Research 21, S433-S433 (2006).
M. H. Lee et al., "Effect of biomaterial surface properties on fibronectin-alpha(5)beta(1) integrin interaction and cellular attachment," Biomaterials 27 (9), 1907-1916 (2006).
S. Radin, J. Parvizi and P. Ducheyne, "Thin sol-gel films on fracture fixation material for the controlled release of antibiotics," Bioceramics 18, Pts 1 and 2 309-311, 759-762 (2006).
G. A. Silva et al., "Starch-based microparticles as a novel strategy for tissue engineering applications," Bioceramics 18, Pts 1 and 2 309-311, 907-910 (2006).
G. K. Toworfe et al., "Initial attachment of osteoblast-like cells on functionalized surfaces coated with calcium phosphate," Bioceramics 18, Pts 1 and 2 309-311, 275-278 (2006).
G. K. Toworfe et al., "Nucleation and growth of calcium phosphate on amine-, carboxyl- and hydroxyl-silane self-assembled monolayers," Biomaterials 27 (4), 631-642 (2006).
J. Yao, S. R. Turteltaub and P. Ducheyne, "A three-dimensional nonlinear finite element analysis of the mechanical behavior of tissue engineered intervertebral discs under complex loads," Biomaterials 27 (3), 377-387 (2006).
V. Grigoriou et al., "Apoptosis and survival of osteoblast-like cells are regulated by surface attachment," J.Biol.Chem. 280 (3), 1733-1739 (2005).
W. Lai et al., "Excretion of resorption products from bioactive glass implanted in rabbit muscle," Journal of Biomedical Materials Research Part a 75A (2), 398-407 (2005).
M. H. Lee et al., "The effect of non-specific interactions on cellular adhesion using model surfaces," Biomaterials 26 (14), 1721-1730 (2005).
S. Radin et al., "In vivo tissue response to resorbable silica xerogels as controlled-release materials," Biomaterials 26 (9), 1043-1052 (2005).
S. Radin et al., "Osteogenic effects of bioactive glass on bone marrow stromal cells," Journal of Biomedical Materials Research Part a 73A (1), 21-29 (2005).
J. Yao et al., "The effect of bioactive glass content on synthesis and bioactivity of composite poly (lactic-co-glycolic acid)," Biomaterials 26 (14), 1935-1943 (2005).
J. Yao et al., "Solution-mediated effect of bioactive glass in poly (lactic-co-glycolic acid)-bioactive glass composites on osteogenesis of marrow stromal cells," Journal of Biomedical Materials Research Part a 75A (4), 794-801 (2005).
J. Yao et al., "The effect of bioactive glass content on synthesis and bioactivity of composite poly (lactic-co-glycolic acid)/bioactive glass substrate for tissue engineering," Biomaterials 26 (14), 1935-1943 (2005).
A. R. El-Ghannam et al., "Model surfaces engineered with nanoscale roughness and RGD tripeptides promote osteoblast activity," J.Biomed.Mater.Res.A. 68 (4), 615-627 (2004).
G. K. Toworfe et al., "Fibronectin adsorption on surface-activated poly(dimethylsiloxane) and its effect on cellular function," J.Biomed.Mater.Res.A. 71 (3), 449-461 (2004).
J. C. Gan et al., "Intervertebral disc tissue engineering II: cultures of nucleus pulposus cells," Clin.Orthop.Relat.Res. (411) (411), 315-324 (2003).
T. Livingston, P. Ducheyne and J. Garino, "In vivo evaluation of a bioactive scaffold for bone tissue engineering," J.Biomed.Mater.Res. 62 (1), 1-13 (2002).
Q. Q. Qiu, P. Ducheyne and P. S. Ayyaswamy, "Bioactive, degradable composite microspheres: effect of filler material on surface reactivity," Ann.N.Y.Acad.Sci. 974, 556-564 (2002).
E. A. Kaufmann et al., "Initial events at the bioactive glass surface in contact with protein-containing solutions," J.Biomed.Mater.Res. 52 (4), 825-830 (2000).
P. D. Bianco, P. Ducheyne and J. M. Cuckler, "Systemic titanium levels in rabbits with a titanium implant in the absence of wear," J.Mater.Sci.Mater.Med. 8 (9), 525-529 (1997).
S. B. Nicoll et al., "In vitro release kinetics of biologically active transforming growth factor-beta 1 from a novel porous glass carrier," Biomaterials 18 (12), 853-859 (1997).
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Leif H. Finkel
Professor of Bioengineering; Member of the Institute for Neurological Sciences; Member of the Institute for Medicine and Engineering; Member of the Institute for Research in Cognitive Science
Email: leif at seas.upenn.edu, leif at neuroengineering.upenn.edu
Personal Website | Research Website
Research Interests: Our lab is devoted to trying to understand computation in real neural circuits, and to applications of these insights to neurological and psychiatric diagnosis and treatment. We are developing biophysical level simulations of neocortex, hippocampus and basal ganglia. Current applications are directed at understanding the alterations in brain function in schizophrenia, seizure disorders, and Parkinson’s disease. An underlying theme is the study of mechanisms of neural oscillations, synchronization, and integration of multiple inputs to a cell. We have close collaborations with colleagues working on electrophysiology, human intracranial EEG and deep brain recording, fMRI, and implanted seizure detection/termination devices. A second focus of the lab is on visual perception. We are particularly interested in neural mechanisms of spatiotemporal pattern recognition and Bayesian integration with a current focus on biological motion perception.
Selected Recent Publications: J. T. Moyer et al., "Implementation of dual simultaneous microelectrode recording systems during deep brain stimulation surgery for Parkinson's disease: Technical note," Stereotact.Funct.Neurosurg. 85 (1), 53-53 (2007).
S. F. Danish et al., "Conventional MRI is inadequate to delineate the relationship between the red nucleus and subthalamic nucleus in Parkinson's disease," Stereotact.Funct.Neurosurg. 84 (1), 12-18 (2006).
M. T. Lazarewicz et al., "Analysis of NMDA-dependent voltage bistability in thin dendritic compartments," Neurocomputing 69 (10-12), 1025-1029 (2006).
M. T. Lazarewicz, S. Das and L. H. Finkel, "Recognition of temporal event sequences by a network of cortical neurons," Neurocomputing 65, 143-151 (2005).
J. A. Wolf, J. T. Moyer and L. H. Finkel, "The role of NMDA currents in state transitions of the nucleus accumbens medium spiny neuron," Neurocomputing 65, 565-570 (2005).
J. A. Wolf et al., "NMDA/AMPA ratio impacts state transitions and entrainment to oscillations in a computational model of the nucleus accumbens medium spiny projection neuron," J.Neurosci. 25 (40), 9080-9095 (2005).
L. H. Finkel, "Neuroengineering models of brain disease," Annu.Rev.Biomed.Eng. 2, 577-606 (2000).
E. D. Menschik and L. H. Finkel, "Cholinergic neuromodulation and Alzheimer's disease: from single cells to network simulations," Prog.Brain Res. 121, 19-45 (1999).
E. D. Menschik and L. H. Finkel, "Neuromodulatory control of hippocampal function: towards a model of Alzheimer's disease," Artif.Intell.Med. 13 (1-2), 99-121 (1998).
S. C. Yen and L. H. Finkel, "Extraction of perceptually salient contours by striate cortical networks," Vision Res. 38 (5), 719-741 (1998).
K. Sakai et al., "Coarse-grain parallel computing for very large scale neural simulations in the NEXUS simulation environment," Comput.Biol.Med. 27 (4), 257-266 (1997).
S. M. Courtney, L. H. Finkel and G. Buchsbaum, "Network simulations of retinal and cortical contributions to color constancy," Vision Res. 35 (3), 413-434 (1995).
K. Sakai and L. H. Finkel, "Characterization of the spatial-frequency spectrum in the perception of shape from texture," J.Opt.Soc.Am.A Opt.Image Sci.Vis. 12 (6), 1208-1224 (1995).
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Kenneth R. Foster
Professor of Bioengineering and Associate Professor of Electrical and Systems Engineering
Email: kfoster at seas.upenn.edu
Personal Website
Research Interests: My interests relate to biomedical applications of nonionizing radiation from audio through microwave frequency ranges, and health and safety aspects of electromagnetic fields as they interact with the body. Another and somewhat broader topic of interest is technological risk, and impact of technology (principally, electrotechnologies) on humans.
Selected Recent Publications: P. R. Wolpe, K. R. Foster, D. D. Langleben, Emerging Lie-Detection Technologies: Promises and Perils, American Journal of Bioethics, 5(2): 111, 2005
H. Bassen, et al. Exposure of medical personnel to electromagnetic fields from open magnetic resonance imaging systems, Health Physics. 89(6):684-689, 2005.
J. E. Moulder, K. R. Foster, L. S. Erdreich, J. P, McNamee, Mobile Phones, Mobile Phone Base Stations, and Cancer: A Review, International Journal of Radiation Biology 81: 189-203 (2005)
K. R. Foster and I. A. Lerch, Collateral Damage to American Science from the War on Terrorism, IEEE Technology and Society Magazine, 24:45-52 (2005).
T. T. Chau and K. R. Foster, Should Children Use Mobile Phones? IEEE Microwave Magazine, 6(4):18-30,2005.
K. R. Foster, Building better lie detectors with neuroscience? IEEE Spectrum 42 (7): 8-8 JUL 2005
K. R. Foster and R. Glaser, Thermal Mechanisms of Interaction of Radiofrequency Energy with Biological Systems With Relevance to Exposure Guidelines. Health Physics 92 (6): 609-620 JUN 2007
K. R. Foster, Radiofrequency Exposure from Wireless LANs, Health Physics 92:289-289 (2007)
K. R. Foster and J. Jaeger, The murky ethics of RFIDs, IEEE Spectrum March 2007.
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Daniel A. Hammer
Alfred G. and Meta A. Ennis Professor of Bioengineering, Chairman, Department of Bioengineering; Professor, Chemical and Biomolecular Engineering; and Member, Institute for Medicine and Engineering
Email: hammer at seas.upenn.edu
Personal Website | Research Website
Research Interests: Understanding and manipulating the behavior of biological systems, biophysics of cell adhesion, virus-cell interactions, soft-bio materials. Our work on cell adhesion is aimed at understanding how the dynamics and strength of cell adhesion is controlled by the physical and chemical properties of cell surface molecules. We use several tools to pursue this relationship. First, we alter the chemistry of adhesion molecules systematically and measure the resulting affect on adhesion in carefully constructed assays. Second, we have developed "cell-free" adhesion assays in which we measure the dynamics of adhesion when adhesion molecules are attached to beads and inert substrata, thus focusing unambiguously on the role of surface adhesion molecules in controlling adhesion. Third, in collaboration with Dr. Rick Waugh (University of Rochester) we have built a calibrated microcantilever to measure the strength of adhesion of individual adhesive bonds. And finally, we have developed a computer algorithm, "adhesive dynamics", in which we can simulate the adhesion of cells to surfaces. This algorithm represents a wonderful tool to test systematically the relationship between adhesion molecule properties and cell adhesion in ways that are not feasible experimentally. Our efforts in cell adhesion research have led to a number of fundamental insights. We have been the first lab to recreate "rolling" - the slow translation of white blood cells over blood vessel walls - in a cell free system. In collaboration with Dr. Tim Springer (Harvard), we were the first to measure the relationship between force and bond dissociation for a bioadhesion molecule. Also, we were the first lab to calculate the complete phase diagram of adhesion, relating adhesion molecule properties to the dynamics of adhesion. Virus-cell interactions: Viruses are fascinating, compact biological packages whose sole goal is to infect host cells. Not only do viruses cause disease, but they can also be used to introduce missing genes into cells (gene therapy). Our lab is focused on the fundamental factors that control viral infection, with a long term goal to increase the efficiency of infection (for gene therapy) or block infection (in viral mediated disease). A step in the viral infection cascade is membrane fusion, where the outer lipid bilayer of the virus fuses with a membrane of the host cells. The coalescence of these two membranes allows the genetic material of the virus to enter the host cell nucleus. This fusion is mediated by proteins on the viral surface, which are designed to cause membrane coalescence, often at low pH. We have been interested in the mechanism of fusion, and how it is controlled by the physical chemistry of the viral adhesion molecules and the lipid chemistry of the cell membranes. Our long-term goal is to reconstitute the fusion activity of viral molecules into larger structures, such as vesicles and cells, and to measure the mechanics and dynamics of fusion using micropipette.
Selected Recent Publications: M. T. Beste and D. A. Hammer, "Steady-state multiplicity in receptor-mediated colloidal adhesion," Journal of Physical Chemistry C 111 (5), 2008-2016 (2007).
P. L. Biancaniello et al., "DNA-mediated phase behavior of microsphere suspensions," Langmuir 23 (5), 2688-2693 (2007).
K. E. Caputo et al., "Adhesive dynamics simulations of the shear threshold effect for leukocytes," Biophys.J. 92 (3), 787-797 (2007).
N. A. Christian et al., "Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling," Bioconjug.Chem. 18 (1), 31-40 (2007).
P. Peter Ghoroghchian et al., "Controlling bulk optical properties of emissive polymersomes through intramembranous polymer-fluorophore interactions," Chemistry of Materials 19 (6), 1309-1318 (2007).
R. Oetama et al., "The effect of cholesterol on the traction force and adhesion area of endothelial cells," Biophys.J. , 633A-633A (2007).
L. A. Smith et al., "Neutrophil traction stresses are concentrated in the uropod during migration," Biophys.J. 92 (7), L58-L60 (2007).
L. A. Smith et al., "Interplay between shear stress and adhesion on neutrophil locomotion," Biophys.J. 92 (2), 632-640 (2007).
C. Blank et al., "Recurrent infections and immunological dysfunction in congenital disorder of glycosylation la (CDG Ia)," J.Inherit.Metab.Dis. 29 (4), 592-592 (2006).
H. Chen et al., "In vivo beta1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines," Genes Dev. 20 (8), 927-932 (2006).
P. P. Ghoroghchian et al., "In vivo optical imaging enabled by soft-matter analogs of the quantum dots," Abstracts of Papers of the American Chemical Society 231, (2006).
P. P. Ghoroghchian et al., "Bioresorbable vesicles formed through spontaneous self-assembly of amphiphilic poly(ethylene oxide)-block-polycaprolactone," Macromolecules 39 (5), 1673-1675 (2006).
P. P. Ghoroghchian et al., "Quantitative membrane loading of polymer vesicles," Soft Matter 2 (11), 973-980 (2006).
D. A. Hammer et al., "Targeting and imaging with polymersomes," Abstracts of Papers of the American Chemical Society 231, (2006).
D. A. Hammer and R. E. Waugh, "Teaching cellular engineering," Ann.Biomed.Eng. 34 (2), 253-256 (2006).
E. F. Krasik, K. L. Yee and D. A. Hammer, "Adhesive dynamics simulation of neutrophil arrest with deterministic activation," Biophys.J. 91 (4), 1145-1155 (2006).
J. J. Lin et al., "Adhesion of antibody-functionalized polymersomes," Langmuir 22 (9), 3975-3979 (2006).
L. R. Pepper, D. A. Hammer and E. T. Boder, "Rolling adhesion of alpha(L) I domain mutants decorrelated from binding affinity," J.Mol.Biol. 360 (1), 37-44 (2006).
K. Sengupta et al., "Spreading of neutrophils: From activation to migration," Biophys.J. 91 (12), 4638-4648 (2006).
J. A. Silas et al., "Mechanics of adhesion at the surface of polymer vesicles," Abstracts of Papers of the American Chemical Society 231, (2006).
Y. Zhang et al., "Differential adhesion of microspheres mediated by DNA hybridization I: Experiment," Biophys.J. 90 (11), 4128-4136 (2006).
H. Aranda-Espinoza, M. Dembo and D. A. Hammer, "The traction stresses of neutrophils during adhesion and chemokinesis," Biophys.J. 88 (1), 540A-540A (2005).
K. E. Caputo and D. A. Hammer, "Effect of microvillus deformability on leukocyte adhesion explored using adhesive dynamics simulations," Biophys.J. 89 (1), 187-200 (2005).
T. J. English and D. A. Hammer, "The effect of cellular receptor diffusion on receptor-mediated viral binding using Brownian adhesive dynamics (BRAD) simulations," Biophys.J. 88 (3), 1666-1675 (2005).
A. O. Eniola and D. A. Hammer, "In vitro characterization of leukocyte mimetic for targeting therapeutics to the endothelium using two receptors," Biomaterials 26 (34), 7136-7144 (2005).
A. O. Eniola and D. A. Hammer, "Characterization of biodegradable drug delivery vehicles with the adhesive properties of leukocytes II: effect of degradation on targeting activity," Biomaterials 26 (6), 661-670 (2005).
A. O. Eniola et al., "I-domain of lymphocyte function-associated antigen-1 mediates rolling of polystyrene particles on ICAM-1 under flow," Biophys.J. 89 (5), 3577-3588 (2005).
P. P. Ghoroghchian et al., "Near-infrared-emissive polymersomes: Self-assembled soft matter for in vivo optical imaging," Proc.Natl.Acad.Sci.U.S.A. 102 (8), 2922-2927 (2005).
P. P. Ghoroghchian et al., "Broad spectral domain fluorescence wavelength modulation of visible and near-infrared emissive polymersomes," J.Am.Chem.Soc. 127 (44), 15388-15390 (2005).
D. A. Hammer, "Leukocyte adhesion: What's the catch?" Current Biology 15 (3), R96-R99 (2005).
D. A. Hammer et al., "Self-assembled polymersomes for targeted biological adhesion," Abstracts of Papers of the American Chemical Society 230, U1214-U1215 (2005).
D. A. Hammer et al., "Traction force microscopy reveals basic mechano-chemical principles of cell adhesion, speading and cell-cell organization." Abstracts of Papers of the American Chemical Society 229, U648-U648 (2005).
D. A. Hammer et al., "Colloidal assembly by using bioadhesion." Abstracts of Papers of the American Chemical Society 229, U727-U727 (2005).
M. King et al., "Nano-to-micro scale dynamics of P-selectin detachment from leukocyte interfaces: Numerical simulation of tethering under flow." Abstracts of Papers of the American Chemical Society 229, U634-U634 (2005).
M. R. King et al., "Nano-to-micro scale dynamics of P-selectin detachment from leukocyte interfaces. III. Numerical simulation of tethering under flow," Biophys.J. 88 (3), 1676-1683 (2005).
J. J. Lin et al., "Adhesion of polymer vesicles," Phys.Rev.Lett. 95 (2), 026101 (2005).
A. Omolola Eniola and D. A. Hammer, "In vitro characterization of leukocyte mimetic for targeting therapeutics to the endothelium using two receptors," Biomaterials 26 (34), 7136-7144 (2005).
M. J. Paszek et al., "Tensional homeostasis and the malignant phenotype," Cancer Cell 8 (3), 241-254 (2005).
C. A. Reinhart-King, M. Dembo and D. A. Hammer, "The dynamics and mechanics of endothelial cell spreading," Biophys.J. 89 (1), 676-689 (2005).
C. A. Reinhart-King, M. Dembo and D. A. Hammer, "The dynamics and mechanics of endothelial cell spreading," Biophys.J. 89 (1), 676-689 (2005).
K. L. Sarratt et al., "GPVI and alpha(2)beta(1) play independent critical roles during platelet adhesion and aggregate formation to collagen under flow," Blood 106 (4), 1268-1277 (2005).
P. J. Willcox et al., "Dynamic heterodimer-functionalized surfaces for endothelial cell adhesion," Biomaterials 26 (23), 4757-4766 (2005).
Y. Zhang, D. A. Hammer and D. J. Graves, "Competitive hybridization kinetics reveals unexpected behavior patterns," Biophys.J. 89 (5), 2950-2959 (2005).
Y. Zhang et al., "Selective detection of DNA molecules with microsphere adhesion system ." Abstracts of Papers of the American Chemical Society 229, U672-U673 (2005).
F. J. Byfield et al., "Cholesterol depletion results in stiffening of aortic endothelial cells as determined by micropipette aspiration analysis and traction force microscopy," J.Gen.Physiol. 124 (1), 15A-16A (2004).
T. J. English and D. A. Hammer, "Brownian adhesive dynamics (BRAD) for simulating the receptor-mediated binding of viruses," Biophys.J. 86 (6), 3359-3372 (2004).
D. A. Hammer et al., "NIR-emissive polymersomes: Self-assembled soft matter for in vivo optical imaging," Abstracts of Papers of the American Chemical Society 228, U212-U212 (2004).
A. L. Hiddessen, D. A. Weitz and D. A. Hammer, "Rheology of binary colloidal structures assembled via specific biological cross-linking," Langmuir 20 (16), 6788-6795 (2004).
J. H. Im et al., "Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation," Cancer Res. 64 (23), 8613-8619 (2004).
E. F. Krasik and D. A. Hammer, "A semianalytic model of leukocyte rolling," Biophys.J. 87 (5), 2919-2930 (2004).
W. L. Lau et al., "Oligomerization of fusogenic peptides promotes membrane fusion by enhancing membrane destabilization," Biophys.J. 86 (1 Pt 1), 272-284 (2004).
J. J. Lin et al., "The effect of polymer chain length and surface density on the adhesiveness of functionalized polymersomes," Langmuir 20 (13), 5493-5500 (2004).
M. J. Paszek et al., "Mechano-signaling in mammary morphogenesis and tumorigenesis," Mol.Biol.Cell 15, 241A-241A (2004).
C. A. Reinhart-King, M. Dembo and D. A. Hammer, "Endothelial cell spreading dynamics," Mol.Biol.Cell 15, 174A-174A (2004).
K. L. Sarratt et al., "Platelet receptor glycoprotein VI-mediated adhesion to type I collagen under hydrodynamic flow," Ann.Biomed.Eng. 32 (7), 970-976 (2004).
Y. Zhang et al., "Specific adhesion of micron-sized colloids to substrate surfaces mediated by oligonucleotide hybridization." Abstracts of Papers of the American Chemical Society 227, U857-U857 (2004).
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Susan S. Margulies
Professor of Bioengineering; Member of the Institute for Medicine and Engineering
Email: margulies at seas.upenn.edu
Personal Website | Research Website
Research Interests: Cells within the body routinely tolerate deformations during activities such as head turning and breathing, yet when cells are deformed beyond a safe limit or injury threshold, function and structure are altered temporarily or even permanently. Our goal is to determine functional and structural injury thresholds in the brain and lung, and use them to understand mechanisms of traumatic brain and lung injury. In addition, our study of the biochemical and molecular biology of injured cells facilitates the development of preventive and therapeutic measures. Because human tissues tend to be inhomogeneous, anisotropic and nonlinear, and the tissues of interest undergo large strains, determining the complex relationship between cellular and macroscopic responses requires an integrated biomechanics approach consisting of several simultaneous rigorous engineering experimental and theoretical analyses. Tissue mechanical properties and injury thresholds are measured and used to develop computational models. These models are used to generalize our experimental cell and tissue findings and determine macroscopic injury mechanisms. Applications of current work are in the areas of traumatic head injury in adults and children, and ventilator-induced lung injury. These studies parallel clinical investigations regarding the treatment and detection of traumatic injury.
Selected Recent Publications: M. J. Brennick, W. B. Gefter and S. S. Margulies, "Mechanical effects of genioglossus muscle stimulation on the pharyngeal airway by MRI in cats," Respir.Physiol.Neurobiol. 156 (2), 154-164 (2007).
J. L. Fisher and S. S. Margulies, "Modeling the effect of stretch and plasma membrane tension on Na+-K+-ATPase activity in alveolar epithelial cells," Am.J.Physiol.Lung Cell.Mol.Physiol. 292 (1), L40-53 (2007).
S. H. Friess et al., "Neurobehavioral functional deficits following closed head injury in the neonatal pig," Exp.Neurol. 204 (1), 234-243 (2007).
R. N. Ichord et al., "Hypoxic-ischemic injury complicates inflicted and accidental traumatic brain injury in young children: the role of diffusion-weighted imaging," J.Neurotrauma 24 (1), 106-118 (2007).
S. Ji and S. S. Margulies, "In vivo pons motion within the skull," J.Biomech. 40 (1), 92-99 (2007).
P. M. Kochanek et al., "Inflicted childhood neurotrauma: New insight into the detection, pathobiology, prevention, and treatment of our youngest patients with traumatic brain injury," J.Neurotrauma 24 (1), 1-4 (2007).
K. J. Cavanaugh, T. S. Cohen and S. S. Margulies, "Stretch increases alveolar epithelial permeability to uncharged micromolecules," American Journal of Physiology-Cell Physiology 290 (4), C1179-C1188 (2006).
B. Coats and S. S. Margulies, "Material properties of porcine parietal cortex," J.Biomech. 39 (13), 2521-2525 (2006).
B. Coats and S. S. Margulies, "Material properties of human infant skull and suture at high rates," J.Neurotrauma 23 (8), 1222-1232 (2006).
B. Coats and S. S. Margulies, "Material properties of human infant skull and suture at high rates," J.Neurotrauma 23 (8), 1222-1232 (2006).
B. Coats and S. S. Margulies, "Material properties of porcine parietal cortex," J.Biomech. 39 (13), 2521-2525 (2006).
B. C. DiPaolo et al., "Cytoskeletal dynamics in alveolar epithelial cells (AECs) during tonic stretch," Faseb Journal 20 (5), A1296-A1296 (2006).
S. Eucker et al., "Hypertonic saline increases cerebral blood flow after traumatic brain injury," J.Neurotrauma 23 (6), 1024-1024 (2006).
N. Ibrahim et al., ""Toddler" porcine model of rapid non-impact head injury," J.Neurotrauma 23 (6), 989-989 (2006).
R. Ichord et al., "Hypoxic ischemic injury complicates traumatic brain injury in young children: The role of diffusion weighted magnetic resonance (DWI) imaging," J.Neurotrauma 23 (6), 1001-1001 (2006).
A. Levchakov et al., "Computational studies of strain exposures in neonate and mature rat brains during closed head impact," J.Neurotrauma 23 (10), 1570-1580 (2006).
G. K. Levine et al., "Sepsis-induced lung injury in rats increases alveolar epithelial vulnerability to stretch," Crit.Care Med. 34 (6), 1746-1751 (2006).
S. Margulies et al., "Shaken baby syndrome: A flawed biomechanical analysis," Forensic Sci.Int. 164 (2-3), 278-279 (2006).
M. Naim et al., "Folate supplementation decreases axonal injury in the piglet model of pediatric head injury," J.Neurotrauma 23 (6), 1001-1001 (2006).
X. Ning et al., "A transversely isotropic viscoelastic constitutive equation for brainstem undergoing finite deformation," J.Biomech.Eng. 128 (6), 925-933 (2006).
X. G. Ning et al., "A transversely isotropic viscoelastic constitutive equation for Brainstem undergoing finite deformation," Journal of Biomechanical Engineering-Transactions of the Asme 128 (6), 925-933 (2006).
Q. Zhu, M. Prange and S. Margulies, "Predicting unconsciousness from a pediatric brain injury threshold," Dev.Neurosci. 28 (4-5), 388-395 (2006).
K. B. Arbogast, S. S. Margulies and C. W. Christian, "Initial neurologic presentation in young children sustaining inflicted and unintentional fatal head injuries - In reply," Pediatrics 116 (6), 1608-1609 (2005).
K. B. Arbogast, S. S. Margulies and C. W. Christian, "Initial neurologic presentation in young children sustaining inflicted and unintentional fatal head injuries," Pediatrics 116 (1), 180-184 (2005).
B. Coats and S. S. Margulies, "High rate material properties of infant cranial bone and suture," J.Neurotrauma 22 (10), 1253-1253 (2005).
S. Eucker et al., "Direction dependence of rotational accelerational injury on cerebrovascular hemodynamics response depends on direction of angular acceleration," J.Neurotrauma 22 (10), 1254-1254 (2005).
S. Friess et al., "Neurobehavioral functional deficits in piglets after nonimpact inertial head injury," J.Neurotrauma 22 (10), 1184-1184 (2005).
A. Gefen et al., "In vivo muscle stiffening under bone compression promotes deep pressure sores," Journal of Biomechanical Engineering-Transactions of the Asme 127 (3), 512-524 (2005).
N. G. Ibrahim, B. Coats and S. S. Margulies, "The response of toddler and infant heads during vigorous shaking," J.Neurotrauma 22 (10), 1207-1207 (2005).
M. J. Paszek et al., "Tensional homeostasis and the malignant phenotype," Cancer.Cell. 8 (3), 241-254 (2005).
A. S. Patel et al., "Paracrine stimulation of surfactant secretion by extracellular ATP in response to mechanical deformation," American Journal of Physiology-Lung Cellular and Molecular Physiology 289 (3), L489-L496 (2005).
J. L. Fisher, I. Levitan and S. S. Margulies, "Plasma membrane surface increases with tonic stretch of alveolar epithelial cells," Am.J.Respir.Cell Mol.Biol. 31 (2), 200-208 (2004).
K. R. Johnson et al., "Extracellular matrix stiffness synergizes with ErbB2 to promote malignant transformation of the breast," Mol.Biol.Cell 15, 301A-301A (2004).
R. Raghupathi et al., "Traumatic axonal injury is exacerbated following repetitive closed head injury in the neonatal pig," J.Neurotrauma 21 (3), 307-316 (2004).
M. T. Prange et al., "Anthropomorphic simulations of falls, shakes, and inflicted impacts in infants," J.Neurosurg. 99 (1), 143-150 (2003).
J. L. Fisher and S. S. Margulies, "Na(+)-K(+)-ATPase activity in alveolar epithelial cells increases with cyclic stretch," Am.J.Physiol.Lung Cell.Mol.Physiol. 283 (4), L737-46 (2002).
M. T. Prange and S. S. Margulies, "Regional, directional, and age-dependent properties of the brain undergoing large deformation," J.Biomech.Eng. 124 (2), 244-252 (2002).
R. Raghupathi and S. S. Margulies, "Traumatic axonal injury after closed head injury in the neonatal pig," J.Neurotrauma 19 (7), 843-853 (2002).
K. J. Cavanaugh Jr, J. Oswari and S. S. Margulies, "Role of stretch on tight junction structure in alveolar epithelial cells," Am.J.Respir.Cell Mol.Biol. 25 (5), 584-591 (2001).
J. Oswari, M. A. Matthay and S. S. Margulies, "Keratinocyte growth factor reduces alveolar epithelial susceptibility to in vitro mechanical deformation," Am.J.Physiol.Lung Cell.Mol.Physiol. 281 (5), L1068-77 (2001).
A. C. Duhaime et al., "Maturation-dependent response of the piglet brain to scaled cortical impact," J.Neurosurg. 93 (3), 455-462 (2000).
S. S. Margulies and K. L. Thibault, "Infant skull and suture properties: measurements and implications for mechanisms of pediatric brain injury," J.Biomech.Eng. 122 (4), 364-371 (2000).
B. Morrison 3rd et al., "Dynamic mechanical stretch of organotypic brain slice cultures induces differential genomic expression: relationship to mechanical parameters," J.Biomech.Eng. 122 (3), 224-230 (2000).
D. J. Tschumperlin and S. S. Margulies, "Alveolar epithelial surface area-volume relationship in isolated rat lungs," J.Appl.Physiol. 86 (6), 2026-2033 (1999).
K. B. Arbogast and S. S. Margulies, "Material characterization of the brainstem from oscillatory shear tests," J.Biomech. 31 (9), 801-807 (1998).
M. J. Brennick et al., "MRI study of regional variations of pharyngeal wall compliance in cats," J.Appl.Physiol. 85 (5), 1884-1897 (1998).
S. S. Margulies et al., "Kinematic response of the neck to voluntary and involuntary flexion," Aviat.Space Environ.Med. 69 (9), 896-903 (1998).
K. L. Thibault and S. S. Margulies, "Age-dependent material properties of the porcine cerebrum: effect on pediatric inertial head injury criteria," J.Biomech. 31 (12), 1119-1126 (1998).
D. J. Tschumperlin and S. S. Margulies, "Equibiaxial deformation-induced injury of alveolar epithelial cells in vitro," Am.J.Physiol. 275 (6 Pt 1), L1173-83 (1998).
K. B. Arbogast et al., "A high-frequency shear device for testing soft biological tissues," J.Biomech. 30 (7), 757-759 (1997).
S. S. Margulies et al., "Finite-element analysis of stress in the canine diaphragm," J.Appl.Physiol. 76 (5), 2070-2075 (1994).
S. S. Margulies, L. E. Thibault and T. A. Gennarelli, "Physical model simulations of brain injury in the primate," J.Biomech. 23 (8), 823-836 (1990).
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David F. Meaney
Professor of Bioengineering, Neurosurgery; Member of the Institute for Medicine and Engineering
Email: dmeaney at seas.upenn.edu
Personal Website | Research Website
Research Interests:
We are part of a very new field at the intersection between molecular neurobiology and biomedical engineering that we term molecular neuroengineering. Molecular neuroengineering uses the tools of molecular and cell biology,computational biology, and bioengineering to understand how the nervous system works at the single cell and molecular scale. There is tremendous clinical potential for work in this area, since knowing the molecular triggering events within a single cell or small multi-cellular networks will provide the earliest possible targets for treating a disease. We build systems to measure the biochemical and genomic response of single cells or cell networks to controlled stimulation that mimic either physical injury or regeneration in the nervous system. We use data from these measurements to build models of how cells of the nervous system will respond following either an injury or during growth, and we use these models to identify key regulating points in the response of these cells that might be targets for reducing the effects of the injury or, alternatively, paths to stimulate growth. We believe the future treatment of disease will become increasingly reliant on information at this scale in the nervous system, simply because it provides the best time to treat a disease. At a more fundamental level, we will also learn how cells in the nervous system can adapt dynamically under even normal, physiological conditions
Selected Recent Publications: M. D'Ascenzo et al., "mGluR5 stimulates gliotransmission in the nucleus accumbens," Proc.Natl.Acad.Sci.U.S.A. 104 (6), 1995-2000 (2007).
M. N. DeRidder et al., "Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition," Neurobiol.Dis. 22 (1), 165-176 (2006).
D. M. Geddes-Klein, K. B. Schiffman and D. F. Meaney, "Mechanisms and consequences of neuronal stretch injury in vitro differ with the model of trauma," J.Neurotrauma 23 (2), 193-204 (2006).
D. M. Geddes-Klein et al., "Pharmacologically induced calcium oscillations protect neurons from increases in cytosolic calcium after trauma," J.Neurochem. 97 (2), 462-474 (2006).
P. C. Georges et al., "Matrices with compliance comparable to that of brain tissue select neuronal over glial growth in mixed cortical cultures," Biophys.J. 90 (8), 3012-3018 (2006).
M. Mesfin et al., "NMDAR subunit activation only influences cell fate in the cortex and hippocampus following experimental traumatic brain injury," J.Neurotrauma 23 (6), 1032-1032 (2006).
W. Mille and D. Meaney, "Calcium wave propagation and ERK activation surrounding regions of mechanical injury in astrocyte cultures," J.Neurotrauma 23 (6), 986-986 (2006).
B. J. Pfister et al., "Development of transplantable nervous tissue constructs comprised of stretch-grown axons," J.Neurosci.Methods 153 (1), 95-103 (2006).
J. Spaethling, D. Geddes-Klein and D. Meaney, "Presence of calcium permeable AMPA receptors following in vitro mechanical injury," J.Neurotrauma 23 (6), 1007-1007 (2006).
D. M. Geddes et al., "NR2A containing NMDA receptors subunits selectively activate the JNK signalling pathway immediately after both trauma and or excitotoxic insults," J.Neurotrauma 22 (10), 1190-1190 (2005).
L. Longhi et al., "Temporal window of vulnerability to repetitive experimental concussive brain injury," Neurosurgery 56 (2), 364-373 (2005).
D. F. Meaney and M. S. Grady, "Should corticosteroids be used to treat traumatic brain injury?" Nature Clinical Practice Neurology 1 (2), 74-75 (2005).
P. Singh et al., "The role of subunit composition in the mechanoactivation of NMDA receptors," J.Neurotrauma 22 (10), 1213-1213 (2005).
X. H. Chen et al., "Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma," Am.J.Pathol. 165 (2), 357-371 (2004).
M. N. DeRidder, R. Raghupathi and D. F. Meaney, "Effects of ifenprodil on the level of calpain and caspase-3 mediated cell death in the hippocampus," J.Neurotrauma 21 (9), 1306-1306 (2004).
D. M. Geddes and D. F. Meaney, "Synaptic NMDA receptors are an initiating factor in the cytosolic calcium response to stretch," J.Neurotrauma 21 (9), 1316-1316 (2004).
A. Iwata et al., "Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors," J.Neurosci. 24 (19), 4605-4613 (2004).
W. R. Ledoux, D. F. Meaney and H. J. Hillstrom, "A quasi-linear, viscoelastic, structural model of the plantar soft tissue with frequency-sensitive damping properties," Journal of Biomechanical Engineering-Transactions of the Asme 126 (6), 831-837 (2004).
T. A. Lusardi et al., "A device to study the initiation and propagation of calcium transients in cultured neurons after mechanical stretch," Ann.Biomed.Eng. 32 (11), 1546-1558 (2004).
W. J. Miller and D. F. Meaney, "Mechanically injured astrocytes activate nearby astrocytes through an ATP-mediated pathway in vitro," J.Neurotrauma 21 (9), 1316-1316 (2004).
B. J. Pfister et al., "Extreme stretch growth of integrated axons," J.Neurosci. 24 (36), 7978-7983 (2004).
B. P. Pfister et al., "Engineering nerve constructs for clinical application," J.Neurotrauma 21 (9), 1288-1288 (2004).
K. K. Schiffman, D. M. Geddes and D. F. Meaney, "Neuronal response to injury varies depending on both magnitude and directionality of applied stretch," J.Neurotrauma 21 (9), 1315-1315 (2004).
A. C. Bain, D. I. Shreiber and D. F. Meaney, "Modeling of microstructural kinematics during simple elongation of central nervous system tissue," J.Biomech.Eng. 125 (6), 798-804 (2003).
T. A. Lusardi et al., "The separate roles of calcium and mechanical forces in mediating cell death in mechanically injured neurons," Biorheology 40 (1-3), 401-409 (2003).
D. F. Meaney, "Relationship between structural modeling and hyperelastic material behavior: application to CNS white matter," Biomech.Model.Mechanobiol 1 (4), 279-293 (2003).
K. E. Saatman et al., "Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in mice," J.Cereb.Blood Flow Metab. 23 (1), 34-42 (2003).
D. H. Smith, D. F. Meaney and W. H. Shull, "Diffuse axonal injury in head trauma," J.Head Trauma Rehabil. 18 (4), 307-316 (2003).
D. H. Smith and D. F. Meaney, "Roller coasters, g forces, and brain trauma: on the wrong track?" J.Neurotrauma 19 (10), 1117-1120 (2002).
A. C. Bain, R. Raghupathi and D. F. Meaney, "Dynamic stretch correlates to both morphological abnormalities and electrophysiological impairment in a model of traumatic axonal injury," J.Neurotrauma 18 (5), 499-511 (2001).
D. H. Smith, J. A. Wolf and D. F. Meaney, "A new strategy to produce sustained growth of central nervous system axons: continuous mechanical tension," Tissue Eng. 7 (2), 131-139 (2001).
J. A. Wolf et al., "Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels," J.Neurosci. 21 (6), 1923-1930 (2001).
A. C. Bain and D. F. Meaney, "Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury," J.Biomech.Eng. 122 (6), 615-622 (2000).
B. Morrison 3rd et al., "Traumatic injury induces differential expression of cell death genes in organotypic brain slice cultures determined by complementary DNA array hybridization," Neuroscience 96 (1), 131-139 (2000).
B. Morrison 3rd et al., "Dynamic mechanical stretch of organotypic brain slice cultures induces differential genomic expression: relationship to mechanical parameters," J.Biomech.Eng. 122 (3), 224-230 (2000).
S. R. Pollack et al., "Numerical model and experimental validation of microcarrier motion in a rotating bioreactor," Tissue Eng. 6 (5), 519-530 (2000).
D. H. Smith et al., "Immediate coma following inertial brain injury dependent on axonal damage in the brainstem," J.Neurosurg. 93 (2), 315-322 (2000).
X. H. Chen et al., "Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig," J.Neuropathol.Exp.Neurol. 58 (6), 588-596 (1999).
J. C. McGowan et al., "Diffuse axonal pathology detected with magnetization transfer imaging following brain injury in the pig," Magn.Reson.Med. 41 (4), 727-733 (1999).
D. I. Shreiber et al., "Experimental investigation of cerebral contusion: histopathological and immunohistochemical evaluation of dynamic cortical deformation," J.Neuropathol.Exp.Neurol. 58 (2), 153-164 (1999).
D. I. Shreiber, D. H. Smith and D. F. Meaney, "Immediate in vivo response of the cortex and the blood-brain barrier following dynamic cortical deformation in the rat," Neurosci.Lett. 259 (1), 5-8 (1999).
D. H. Smith et al., "Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig," J.Neuropathol.Exp.Neurol. 58 (9), 982-992 (1999).
D. H. Smith et al., "High tolerance and delayed elastic response of cultured axons to dynamic stretch injury," J.Neurosci. 19 (11), 4263-4269 (1999).
K. M. Cecil et al., "High-field proton magnetic resonance spectroscopy of a swine model for axonal injury," J.Neurochem. 70 (5), 2038-2044 (1998).
D. H. Smith et al., "Magnetic resonance spectroscopy of diffuse brain trauma in the pig," J.Neurotrauma 15 (9), 665-674 (1998).
D. H. Smith et al., "Characterization of diffuse axonal pathology and selective hippocampal damage following inertial brain trauma in the pig," J.Neuropathol.Exp.Neurol. 56 (7), 822-834 (1997).
H. Kimura et al., "Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation," J.Comput.Assist.Tomogr. 20 (4), 540-546 (1996).
T. K. McIntosh et al., "Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms," Lab.Invest. 74 (2), 315-342 (1996).
D. T. Ross et al., "Distribution of forebrain diffuse axonal injury following inertial closed head injury in miniature swine," Exp.Neurol. 126 (2), 291-299 (1994).
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Steven Nicoll
Assistant Professor of Bioengineering and Orthopaedic Surgery; Member of the Institute for Medicine and Engineering
Email: nicoll at seas.upenn.edu
Personal Website
Research Interests: Epigenetic Control of Cellular Phenotype: Recent advances in tissue engineering have increased the need for specialized cell populations to promote tissue regeneration. Embryonic stem cells have been investigated for such applications and hold great therapeutic promise. However, practical and ethical considerations may ultimately limit the widespread use of such progenitor cells. Our approach involves the conversion of skin cells, specifically human dermal fibroblasts, to specialized cell types by regulating environmental cues such as oxidative and mechanical stresses that govern cell differentiation. Thus far, we have successfully induced dermal fibroblasts to differentiate into chondrocytes (i.e., cartilage cells) and are currently using these cells to engineer articular cartilage. We are extending these studies to explore whether such fibroblasts may give rise to other cell types (i.e., bone and muscle-forming cells) by modulation of similar epigenetic pathways. Biomimetic Scaffolds for Connective Tissue Repair: The success of implantable materials depends heavily upon their ability to integrate with surrounding host tissue. The incorporation of growth factors into carrier materials as well as the immobilization of bioactive peptides which mimic the cell binding domains of extracellular matrix macromolecules are current approaches that we use to promote cell adhesion and improve implant fixation and stability. A particular class of collagen mimetic peptides has been shown to stimulate cell attachment and differentiation on clinically relevant biomaterials. The interaction of these collagen-like peptides with cell surface receptors and their potential to generate precise, three-dimensional cellular architectures are being characterized on materials used in the development of living tissue surrogates. Transcriptional and Genetic Determinants of Chondrogenesis: We utilize an in vitro model system for cartilage differentiation developed in our laboratory to explore signal transduction pathways and identify novel genes involved in chondrogenesis. Expanding on previous work with the transforming growth factor-ß (TGF-ß) family of polypeptide cytokines, we study the role of transcription factors that act downstream of pathways mediated by TGF-ß family members. In addition, we are attempting to isolate regulatory genes essential to cartilage formation using a variety of techniques including differential display reverse-transcription-PCR and gene microarray analyses. Cloning of such genes may result in the discovery of novel growth and morphogenetic factors that may be of use in clinical orthopaedics.
Selected Recent Publications: C. S. Yerramalli et al., "The effect of nucleus pulposus crosslinking and glycosaminoglycan degradation on disc mechanical function," Biomech.Model.Mechanobiol 6 (1-2), 13-20 (2007).
H. E. Brink et al., "Serum-dependent effects on adult and fetal tendon fibroblast migration and collagen expression," Wound Repair Regen. 14 (2), 179-186 (2006).
A. I. Chou et al., "The effect of serial monolayer passaging on the collagen expression profile of outer and inner anulus fibrosus cells," Spine 31 (17), 1875-1881 (2006).
C. K. Hee, M. A. Jonikas and S. B. Nicoll, "Influence of three-dimensional scaffold on the expression of osteogenic differentiation markers by human dermal fibroblasts," Biomaterials 27 (6), 875-884 (2006).
H. E. Brink, S. S. Stalling and S. B. Nicoll, "Influence of serum on adult and fetal dermal fibroblast migration, adhesion, and collagen expression," In Vitro Cell.Dev.Biol.Anim. 41 (8-9), 252-257 (2005).
J. Jiang, S. B. Nicoll and H. H. Lu, "Co-culture of osteoblasts and chondrocytes modulates cellular differentiation in vitro," Biochem.Biophys.Res.Commun. 338 (2), 762-770 (2005).
A. J. Wheaton et al., "Quantification of cartilage biomechanical and biochemical properties via T-1p magnetic," Magnetic Resonance in Medicine 54 (5), 1087-1093 (2005).
I. P. Basalo et al., "Cartilage interstitial fluid load support in unconfined compression following enzymatic digestion," Journal of Biomechanical Engineering-Transactions of the Asme 126 (6), 779-786 (2004).
A. J. Wheaton et al., "Noninvasive measurement of cartilage biomechanics using T-1 beta MRI," Osteoarthritis and Cartilage 12, S21-S21 (2004).
S. B. Nicoll et al., "In vitro release kinetics of biologically active transforming growth factor-beta 1 from a novel porous glass carrier," Biomaterials 18 (12), 853-859 (1997).
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Ravi Radhakrishnan
Assistant Professor of Bioengineering
Email: rradhak at seas.upenn.edu
Personal Website | Research Website
Research Interests: Studying biochemical phenomena at various length and timescales from electronic structure to signaling pathways by employing tools from Computational Biology, Statistical Mechanics, and Quantum Mechanics. Dr. Radhakrishnan's research lies in the interface of chemical physics and molecular biology and is currently focused on various biophysical and biochemical problems spanning carcinogenesis, therapeutic inhibition of signaling enzymes, RNA catalysis, membrane phenomena, and targeted drug delivery.
Selected Recent Publications: R. Radhakrishnan, Coupling of Fast and Slow Modes in the Reaction Pathway of the Minimal Hammerhead Ribozyme Cleavage, 2007, Biophys J., in press. Scheduled to appear in issue 93(7).
Y. Liu et al., "A Multiscale Computational Approach to Dissect Early Events in the Erb Family Receptor Mediated Activation, Differential Signaling, and Relevance to Oncogenic Transformations," Ann.Biomed.Eng. 35 (6), 1012-1025 (2007).
R. Radhakrishnan and R. Venkatramani, "Oxidative damage and active site pre-organization during nucleotide incorporation in DNA by a high fidelity polymerase." Biophys.J. , 645A-645A (2007).
C. Alba-Simionesco et al., "Effects of confinement on freezing and melting," Journal of Physics-Condensed Matter 18 (6), R15-R68 (2006).
R. Radhakrishnan and T. Schlick, "Correct and incorrect nucleotide incorporation pathways in DNA polymerase beta," Biochem.Biophys.Res.Commun. 350 (3), 521-529 (2006).
J. Weinstein and R. Radhakrishnan, "'KMC-TDGL' - A coarse-grained methodology for simulating interfacial dynamics in complex fluids: application to protein-mediated membrane processes," Mol.Phys. 104 (22-24), 3653-3666 (2006).
B. J. Anderson et al., "Molecular computations for predictions of clathrate-hydrate nucleation and phase-behavior of multi-component hydrates." Abstracts of Papers of the American Chemical Society 229, U593-U593 (2005).
C. S. Lo, R. Radhakrishnan and B. L. Trout, "Application of transition path sampling methods in catalysis: A new mechanism for C-C bond formation in the methanol coupling reaction in chabazite," Catalysis Today 105 (1), 93-105 (2005).
R. Radhakrishnan, J. W. Chu and B. L. Trout, "Water structuring in phase transitions and in chemical reactions at sulfur sites in proteins." Abstracts of Papers of the American Chemical Society 229, U786-U786 (2005).
R. Radhakrishnan and T. Schlick, "Fidelity discrimination in DNA polymerase beta: Differing closing profiles for a mismatched (G : A) versus matched (G : C) base pair," J.Am.Chem.Soc. 127 (38), 13245-13252 (2005).
R. Radhakrishnan and T. Schlick, "Fidelity discrimination in DNA polymerase beta: differing closing profiles for a mismatched (G:A) versus matched (G:C) base pair," J.Am.Chem.Soc. 127 (38), 13245-13252 (2005).
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Casim A. Sarkar
Assistant Professor of Bioengineering
Email: casarkar at seas.upenn.edu
| Research Website
Research Interests: Molecular cell engineering: rational design and directed evolution of proteins; cytokine/receptor binding and trafficking; cell signaling and decision-making; computational, synthetic, and systems biology.
Selected Recent Publications: Kubetzko, S*; Sarkar, CA*; Plückthun, A. Protein PEGylation decreases observed target association rates via a dual blocking mechanism. Molecular Pharmacology, 68:1439-1454. 2005. *equally contributed
Sarkar, CA; Lowenhaupt, K; Wang, PJ; Horan, T; Lauffenburger, DA. Parsing the effects of binding, signaling, and trafficking on the mitogenic potencies of granulocyte colony-stimulating factor analogues. Biotechnology Progress, 19:955-964. 2003.
Ricci, MS; Sarkar, CA; Fallon, EM; Lauffenburger, DA; Brems, DN. pH dependence of structural stability of interleukin-2 and granulocyte colony-stimulating factor. Protein Science, 12:1030-1038. 2003.
Sarkar, CA; Lauffenburger, DA. Cell-level pharmacokinetic model of granulocyte colony-stimulating factor: implications for ligand lifetime and potency in vivo. Molecular Pharmacology, 63:147-158. 2003.
Sarkar, CA; Lowenhaupt, K; Horan, T; Boone, TC; Tidor, T; Lauffenburger, DA. Rational cytokine design for increased lifetime and enhanced potency using pH-activated 'histidine switching'. Nature Biotechnology, 20:908-913. 2002.
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John C. Schotland
Associate Professor of Bioengineering
Email: schotland at seas.upenn.edu
Personal Website
Research Interests: Dr. Schotland's research is focused on theoretical optical physics with applications to biomedical imaging and nano-optics. Areas of current interest include optical tomography, optical imaging of nanoscale systems, and the use of quantum states of light for optical imaging. Inverse problems, particularly inverse scattering problems, are a unifying theme which connects these areas.
Selected Recent Publications: A. D. Kim and J. C. Schotland, "Self-consistent scattering theory for the radiative transport equation," Journal of the Optical Society of America A-Optics Image Science and Vision 23 (3), 596-602 (2006).
G. Panasyuk, J. C. Schotland and V. A. Markel, "Radiative transport equation in rotated reference frames," Journal of Physics A-Mathematical and General 39 (1), 115-137 (2006).
G. Y. Panasyuk et al., "Nonlinear inverse scattering and three-dimensional near-field optical imaging," Appl.Phys.Lett. 89 (22), 221116 (2006).
J. Sun, P. S. Carney and J. C. Schotland, "Near-field scanning optical tomography: A nondestructive method for three-dimensional nanoscale imaging," Ieee Journal of Selected Topics in Quantum Electronics 12 (6), 1072-1082 (2006).
D. R. Lytle et al., "Generalized optical theorem for reflection, transmission, and extinction of power for electromagnetic fields," Physical Review E 71 (5), 056610 (2005).
V. A. Markel and J. C. Schotland, "Multiple projection optical diffusion tomography with plane wave illumination," Phys.Med.Biol. 50 (10), 2351-2364 (2005).
V. A. Markel and J. C. Schotland, "Multiple projection optical diffusion tomography with plane wave illumination," Phys.Med.Biol. 50 (10), 2351-2364 (2005).
G. Y. Panasyuk, V. A. Markel and J. C. Schotland, "Superresolution and corrections to the diffusion approximation in optical tomography," Appl.Phys.Lett. 87 (10), 101111 (2005).
Z. M. Wang et al., "Experimental demonstration of an analytic method for image reconstruction in optical diffusion tomography with large data sets," Opt.Lett. 30 (24), 3338-3340 (2005).
Z. M. Wang et al., "Experimental demonstration of an analytic method for image reconstruction in optical diffusion tomography with large data sets," Opt.Lett. 30 (24), 3338-3340 (2005).
A. M. Zysk, P. S. Carney and J. C. Schotland, "Eikonal method for calculation of coherence functions," Phys.Rev.Lett. 95 (4), 043904 (2005).
V. A. Markel and J. C. Schotland, "Symmetries, inversion formulas, and image reconstruction for optical tomography," Physical Review E 70 (5), 056616 (2004).
V. A. Markel and J. C. Schotland, "Symmetries, inversion formulas, and image reconstruction for optical tomography," Phys.Rev.E.Stat.Nonlin Soft Matter Phys. 70 (5 Pt 2), 056616 (2004).
V. A. Markel and J. C. Schotland, "Dual-projection optical diffusion tomography," Opt.Lett. 29 (17), 2019-2021 (2004).
M. A. Elliott et al., "Spectral quantitation by principal component analysis using complex singular value decomposition," Magn.Reson.Med. 41 (3), 450-455 (1999).
E. K. Insko et al., "Generalized reciprocity," J.Magn.Reson. 131 (1), 111-117 (1998).
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Andrew Tsourkas
Assistant Professor of Bioengineering, Member of the Institute of
Medicine and Engineering, Secondary Appointment in Radiology
Email: atsourk at seas.upenn.edu
Personal Website | Research Website
Research Interests: Developing novel molecular imaging probes to study genetic and protein expression profiles via fluorescence, bioluminescence, and magnetic resonance imaging. Dr. Tsourkas' current research focuses on the detection of gene expression using novel oligonucleotide-based fluorescent probes, targeting molecular markers of disease with magneto-optical nanoparticles, and using molecular reporters to monitor cell signaling pathways.
Selected Recent Publications: Chen, A.K, Behlke, M.A., Tsourkas, A. (2007) Avoiding false-positive signals with nuclease-vulnerable molecular beacons in single living cells. Accepted.
J. Czupryna and A. Tsourkas, "Suicide gene delivery by calcium phosphate nanoparticles - A novel method of targeted therapy for gastric cancer," Cancer Biology & Therapy 5 (12), 1691-1692 (2006).
D. L. Thorek et al., "Superparamagnetic iron oxide nanoparticle probes for molecular imaging," Ann.Biomed.Eng. 34 (1), 23-38 (2006).
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Beth A. Winkelstein
Associate Professor in Bioengineering, Neurosurgery; Member of the Institute for Medicine and Engineering
Email: winkelst at seas.upenn.edu
Personal Website | Research Website
Research Interests: Understanding the mechanisms of injury that produce whiplash, sports-related, and other painful injuries. Particular emphasis is placed on understanding injury to individual structures in the neck, such as the facet joints, nerve roots and spinal cord and how mechanical loading to these structures elicits pain. Research efforts incorporate modeling, computational modeling, injury analysis and neuroimmunologic techniques, among others, to begin to develop thresholds for mechanical injury that produce persistent pain; and work towards a definition of the neck's tolerance for painful injury.
Selected Recent Publications: Quinn KP and Winkelstein BA. "Cervical Facet Capsular Ligament Yield Defines the Threshold for Injury and Persistent Joint-Mediated Neck Pain." Journal of Biomechanics, 40(10), 2299-2306 (2007).
K. E. Lee et al., "Tensile cervical facet capsule ligament mechanics: failure and subfailure responses in the rat," J.Biomech. 39 (7), 1256-1264 (2006).
Simon S, Davis, M, Odner D, Udupa J, Winkelstein B, "CT Imaging Techniques for Describing Motions of the Cervicothoracic Junction and Cervical Spine During Flexion, Extension and Cervical Traction,"Spine, 31(1):44-50, 2006.
K. P. Quinn and B. A. Winkelstein, "Cervical facet capsular ligament yield defines the threshold for injury and persistent joint-mediated neck pain," J.Biomech. , (2006).
S. M. Rothman, R. A. Kreider and B. A. Winkelstein, "Spinal neuropeptide responses in persistent and transient pain following cervical nerve root injury," Spine 30 (22), 2491-2496 (2005).
S. M. Rothman and B. A. Winkelstein, "Cervical nerve root injury differentially upregulates spinal TNF at early time points for persistent and resolving pain in a rat model," J.Neurotrauma 22 (10), 1237-1237 (2005).
R. D. Hubbard and B. A. Winkelstein, "Early rhizotomy after painful dorsal root compression reduces behavioral hypersensitivity and spinal glial activation in a rat model," J.Neurotrauma 22 (10), 1215-1215 (2005).
R. D. Hubbard and B. A. Winkelstein, "Transient cervical nerve root compression in the rat induces bilateral forepaw allodynia and spinal glial activation: mechanical factors in painful neck injuries," Spine 30 (17), 1924-1932 (2005).
K. E. Lee et al., "Spinal expression of substance P and its receptor in cervical facet joint-mediated injury: Preliminary findings in a model of persistent neck pain," J.Neurotrauma 22 (10), 1169-1169 (2005).
K. E. Lee et al., "A novel rodent neck pain model of facet-mediated behavioral hypersensitivity: implications for persistent pain and whiplash injury," J.Neurosci.Methods 137 (2), 151-159 (2004).
B. A. Winkelstein, "Mechanisms of central sensitization, neuroimmunology & injury biomechanics in persistent pain: implications for musculoskeletal disorders," J.Electromyogr.Kinesiol. 14 (1), 87-93 (2004).
B. A. Winkelstein and J. A. DeLeo, "Mechanical thresholds for initiation and persistence of pain following nerve root injury: mechanical and chemical contributions at injury," J.Biomech.Eng. 126 (2), 258-263 (2004).
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Chemical and Biomolecular Engineering
Eric T. Boder
Assistant Professor of Chemical and Biomolecular Engineering
Email: boder at seas.upenn.edu
Personal Website | Research Website
Research Interests: Development and optimization of proteins as therapeutic agents; engineering the immune response; biophysics and structural biology of immunological receptors; high affinity protein binding. Proteins are naturally occurring polymers comprised of amino acid subunits. The advantage of these molecules is their ability to catalyze a wide range of complex chemistries and engage in countless exquisitely specific molecular interactions, yet each protein is itself constructed from a single synthetic chemistry and its function is perfectly contained within a simple genetic code. The ability of this class of molecule to perform highly complex tasks, combined with their relative ease of synthesis by microorganisms, has spurred the development of an industry pursuing the use of proteins in separations, diagnostics, and numerous medical therapies. Protein pharmaceuticals, also called biopharmaceuticals, represent a rapidly developing product area in industry. In many cases, the extreme specificity of molecular interations required to inhibit certain disease states has limited the success of small organic pharmaceuticals in treatment. Protein reagents have the potential to overcome this obstacle; however, the utility of proteins as therapeutic agents has been limited by the lack of a quantitative engineering approach to developing proteins with the appropriate molecular properties. My goal is to develop a program of research addressing this need. This research must consider several critical points: 1. Selection of a molecular scaffold with properties suitable for the intended application (e.g, tissue penetration properties, thermal stability); 2. Development of protein engineering processes for quantitatively altering the functional properties of the chosen reagent to optimize for the specific application; 3. Quantitative analysis of the relevant molecular properties and combination of this knowledge with protein engineering processes for molecular design. A particular target application of this research is engineering the immune response. Numerous devastating diseases result from destruction of the body's own tissues due to attack by the cellular immune system (autoimmunity). Misidentification of self in autoimmunity and immunological attack of transplanted tissues, as well as failure of the immune system to identify certain harmful entities (e.g., certain viruses or tumor cells), is essentially a problem of molecular recognition. Inhibiting undesirable immune responses or stimulating immune responses against novel targets are problems most likely to be solved by taking advantage of the unique properties of engineered protein reagents. Research in this area makes use of tools from molecular biology, protein chemistry, and biophysics.
Selected Recent Publications:
R. Parthasarathy, S. Subramanian and E. T. Boder, "Sortase A as a novel molecular "stapler" for sequence-specific protein conjugation," Bioconjug.Chem. 18 (2), 469-476 (2007).
S. Subramanian, E. T. Boder and D. E. Discher, "Phylogenetic divergence of CD47 interactions with human signal regulatory protein alpha reveals locus of species specificity - Implications for the binding site," J.Biol.Chem. 282 (3), 1805-1818 (2007).
P. Derr, E. Boder and M. Goulian, "Changing the specificity of a bacterial chemoreceptor," J.Mol.Biol. 355 (5), 923-932 (2006).
S. Park et al., "Limitations of yeast surface display in engineering proteins of high thermostability," Protein Engineering Design & Selection 19 (5), 211-217 (2006).
R. Parthasarathy et al., "Post-translational regulation of expression and conformation of an immunoglobulin domain in yeast surface display," Biotechnol.Bioeng. 93 (1), 159-168 (2006).
L. R. Pepper, D. A. Hammer and E. T. Boder, "Rolling adhesion of alpha(L) I domain mutants decorrelated from binding affinity," J.Mol.Biol. 360 (1), 37-44 (2006).
S. Subramanian et al., "Species- and cell type-specific interactions between CD47 and human SIRP alpha," Blood 107 (6), 2548-2556 (2006).
E. T. Boder et al., "Yeast surface display of a noncovalent MHC class II heterodimer complexed with antigenic peptide," Biotechnol.Bioeng. 92 (4), 485-491 (2005).
S. Park, E. T. Boder and J. G. Saven, "Modulating the DNA affinity of Elk-1 with computationally selected mutations," J.Mol.Biol. 348 (1), 75-83 (2005).
S. Park et al., "Progress in the development and application of computational methods for probabilistic protein design," Comput.Chem.Eng. 29 (3), 407-421 (2005).
R. Parthasarathy, J. Bajaj and E. T. Boder, "An immobilized biotin ligase: Surface display of Escherichia coli BirA on Saccharomyces cerevisiae," Biotechnol.Prog. 21 (6), 1627-1631 (2005).
J. H. Lee et al., "Developing nanomachines via engineering of novel membrane protein," Protein Science 13, 154-155 (2004).
A. W. Nields, S. Park and E. T. Boder, "Heterogeneous truncation of yeast-secreted heterologous proteins," Protein Science 13, 99-100 (2004).
S. Subramanian et al., "CD47-mediated phagocytosis inhibition: Signaling and molecular determinants," Mol.Biol.Cell 15, 65A-65A (2004).
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John C. Crocker
Associate Professor of Chemical and Biomolecular Engineering and Skirkanich Associate Professor of Innovation in Chemical Engineering
Email: jcrocker at seas.upenn.edu
Personal Website
Research Interests: Microrheology of biopolymers, recA searching, 3-D microscopy, device biophysics. Dr. Crocker's research seeks to understand the feedback of mechanical force or stress with biochemistry on the cellular and macromolecular scales and to use the results to engineer useful devices for medical and biochemical applications.
Selected Recent Publications: P. L. Biancaniello et al., "DNA-mediated phase behavior of microsphere suspensions," Langmuir 23 (5), 2688-2693 (2007).
P. L. Biancaniello and J. C. Crocker, "Line optical tweezers instrument for measuring nanoscale interactions and kinetics," Rev.Sci.Instrum. 77 (11), 113702 (2006).
F. J. Byfield et al., "Evidence for the role of cell stiffness in modulation of volume-regulated anion channels," Acta Physiologica 187 (1-2), 285-294 (2006).
M. L. Gardel et al., "Stress-dependent elasticity of composite actin networks as a model for cell behavior," Phys.Rev.Lett. 96 (8), 088102 (2006).
M. L. Gardel et al., "Prestressed F-actin networks cross-linked by hinged filamins replicate mechanical properties of cells," Proc.Natl.Acad.Sci.U.S.A. 103 (6), 1762-1767 (2006).
B. D. Hoffman et al., "The consensus mechanics of cultured mammalian cells," Proc.Natl.Acad.Sci.U.S.A. 103 (27), 10259-10264 (2006).
A. J. Kim, P. L. Biancaniello and J. C. Crocker, "Engineering DNA-mediated colloidal crystallization," Langmuir 22 (5), 1991-2001 (2006).
J. Liu et al., "Microrheology probes length scale dependent rheology," Phys.Rev.Lett. 96 (11), 118104 (2006).
K. M. Van Citters et al., "The role of F-actin and myosin in epithelial cell rheology," Biophys.J. 91 (10), 3946-3956 (2006).
P. L. Biancaniello, A. J. Kim and J. C. Crocker, "Colloidal interactions and self-assembly using DNA hybridization," Phys.Rev.Lett. 94 (5), 058302 (2005).
B. D. Hoffman et al., "Cytoskeletal rheology and forced unfolding of cross-link protein domains," Biophys.J. 88 (1), 493A-493A (2005).
S. S. Kapur et al., "Role of configurational entropy in the thermodynamics of clusters of point defects in crystalline solids," Physical Review B 72 (1), 014119 (2005).
A. J. Kim, V. N. Manoharan and J. C. Crocker, "Swelling-based method for preparing stable, functionalized polymer colloids," J.Am.Chem.Soc. 127 (6), 1592-1593 (2005).
K. A. Miranda et al., "Measuring cytoskeleton mechanics and its relationship to the actin model," Biophys.J. 88 (1), 493A-493A (2005).
M. P. Valignat et al., "Reversible self-assembly and directed assembly of DNA-linked micrometer-sized colloids," Proc.Natl.Acad.Sci.U.S.A. 102 (12), 4225-4229 (2005).
J. C. Crocker, P. Biancaniello and A. J. Kim, "Measuring and modeling weak adhesion between DNA-grafted colloids." Abstracts of Papers of the American Chemical Society 228, U489-U489 (2004).
D. T. Chen et al., "Rheological microscopy: local mechanical properties from microrheology," Phys.Rev.Lett. 90 (10), 108301 (2003).
A. W. Lau et al., "Microrheology, stress fluctuations, and active behavior of living cells," Phys.Rev.Lett. 91 (19), 198101 (2003).
K. Lin et al., "Colloidal interactions in suspensions of rods," Phys.Rev.Lett. 87 (8), 088301 (2001).
R. J. Owen et al., "Measurement of long-range steric repulsions between microspheres due to an adsorbed polymer," Phys.Rev.E.Stat.Nonlin Soft Matter Phys. 64 (1 Pt 1), 011401 (2001).
J. C. Crocker et al., "Two-point microrheology of inhomogeneous soft materials," Phys.Rev.Lett. 85 (4), 888-891 (2000).
Kh Lin et al., "Entropically driven colloidal crystallization on patterned surfaces," Phys.Rev.Lett. 85 (8), 1770-1773 (2000).
E. R. Weeks et al., "Three-dimensional direct imaging of structural relaxation near the colloidal glass transition," Science 287 (5453), 627-631 (2000).
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Scott L. Diamond
Arthur E. Humphrey Professor of Chemical and Biomolecular Engineering and Bioengineering; Associate Director and Charter Member of Institute for Medicine and Engineering; Director of Biotechnology Program
Email: sld at seas.upenn.edu
Personal Website | Research Website
Research Interests: Mechano-biology, blood clotting and blood clot dissolving reactions, pharmacodynamics of thrombolytic therapies, endothelial gene therapy, proteomics of blood. Endothelial Cell Mechanobiology: This research ultilizes molecular and cell biology approches to explore issues related to cardiovascular disease of the arterial system. Our focus is on how physical forces generated by blood flow (hemodynamics) regulate blood vessel wall biology. Vascular surgeons and pathologists have long recognized that atherosclerotic lesions are localized at sites of low and disturbed blood flow. Additionally, physiologists have recognized that the endothelium plays an important role in matching the vessel diameter to the blood flow through vessel. Yet how does an endothelial cell respond to its hemodynamic environment? To date, our investigations have shown that the expression of several genes is altered in complete ways when endothelial cells are exposed to arterial levels of physical forces. We are interested in defining and promoting the hemodynamic regulation of endothelial phenotypes associated with enhanced vasodilatory activity and smooth muscle cell growth antagonism. Thrombosis and Thrombolytics: Thrombolytic therapy is well established in the US as a treatment for acute MI as well as for peripheral arterial and venous thrombosis. Thrombolytic treatment of stroke is in the developmental stage. A goal of our research is the advancement of large scale computations to simulate intravenous, intracoronary, or intrathrombic delivery of a combination of lytic agents to a given clot structure/comoposition for coronary, peripheral artery, and venous thrombolysis. We are conducting experimental and theoretical investigations of blood clotting and blood clot dissolving reactions under realistic hemodynamic conditions. We seek to define the quantitative relationship between the pharmacodynamics of a given thrombolytic therapy, the composition and location of a thrombus, and the consequent reperfusion time and flow rate. Particular attention is placed on the penetration rates of plasma constituents into thrombi (driven by hemodynamic pressures) and the consequent dissolution dynamics. We are advancing the use of computer simulation of the clot dissolving reactions using biphasic, multicomponent convection-dispersion-reaction equations for erodible fibrin structures with heterogeneous adsorption and reaction. Additionally, the design of catheters for local thrombolytics requires accurate understanding of coupled reaction-transport processes. Endothelial Gene Therapy: Gene transfer by nonviral methodologies (e.g. lipofection) are not efficient in cell populations with low mitotic rates. Unfortunately, cells are not actively dividing in many in vivo tissues that are potential clinical targets for gene therapy. While receptor targeting, fusigenic peptides, or endosome disrupting agents help overcome some of the first barriers that limit liposome-based gene delivery, virus free gene transfer using liposomes will have limited clinical utility because of the difficulty of transporting genetic material into the nucleus of a nondividing cell. We propose research to understand and potentially overcome this final rate limit of nuclear entry encounted with lipofection of nondividing cells. We seek to develop methodologies for delivering large genetic packages into the nucleus of nondividing cells. This will be critical for the success of nonviral mediated gene therapy in vivo and various tissue engineering applications where the low mitotic index of target cells would greatly limits the impact of many potential therapies.
Selected Recent Publications: S. L. Diamond, "Methods for mapping protease specificity," Curr.Opin.Chem.Biol. 11 (1), 46-51 (2007).
J. A. Gruneich and S. L. Diamond, "Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagents," J.Gene Med. 9 (5), 381-391 (2007).
R. G. Handwerger and S. L. Diamond, "Biotinylated photocleavable polyethylenimine: capture and triggered release of nucleic acids from solid supports," Bioconjug.Chem. 18 (3), 717-723 (2007).
B. R. Murphy et al., "Delivery and mechanistic considerations for the production of knock-in mice by single-stranded oligonucleotide gene targeting," Gene Ther. 14 (4), 304-315 (2007).
K. Ganguly et al., "Fibrin affinity of erythrocyte-coupled tissue-type plasminogen activators endures hemodynamic forces and enhances fibrinolysis in vivo," J.Pharmacol.Exp.Ther. 316 (3), 1130-1136 (2006).
D. N. Gosalia et al., "Functional phenotyping of human plasma using a 361-fluorogenic substrate biosensing microarray," Biotechnol.Bioeng. 94 (6), 1099-1110 (2006).
K. Y. Horiuchi et al., "Microarrays for the functional analysis of the chemical-kinase interactome," Journal of Biomolecular Screening 11 (1), 48-56 (2006).
M. S. Kim and S. L. Diamond, "Controlled release of DNA," Bioorg.Med.Chem.Lett. 16 (21), 5572-5575 (2006).
M. S. Kim and S. L. Diamond, "Controlled release of DNA/polyamine complex by photoirradiation of a solid phase presenting o-nitrobenzyl ether tethered spermine or polyethyleneimine," Bioorg.Med.Chem.Lett. 16 (21), 5572-5575 (2006).
M. S. Kim and S. L. Diamond, "Photocleavage of o-nitrobenzyl ether derivatives for rapid biomedical release applications," Bioorg.Med.Chem.Lett. 16 (15), 4007-4010 (2006).
I. J. Laurenzi, J. D. Bartels and S. L. Diamond, "Regression of multicomponent sticking probabilities using a genetic algorithm," Ind Eng Chem Res 45 (16), 5482-5488 (2006).
U. M. Okorie and S. L. Diamond, "Matrix protein microarrays for spatially and compositionally controlled microspot thrombosis under laminar flow," Biophys.J. 91 (9), 3474-3481 (2006).
K. E. Edmondson, W. S. Denney and S. L. Diamond, "Neutrophil-bead collision assay: pharmacologically induced changes in membrane mechanics regulate the PSGL-1/P-selectin adhesion lifetime," Biophys.J. 89 (5), 3603-3614 (2005).
D. N. Gosalia et al., "High throughput substrate specificity profiling of serine and cysteine proteases using solution-phase fluorogenic peptide microarrays," Mol.Cell.Proteomics 4 (5), 626-636 (2005).
D. N. Gosalia et al., "Profiling serine protease substrate specificity with solution phase fluorogenic peptide microarrays," Proteomics 5 (5), 1292-1298 (2005).
K. Y. Horiuchi et al., "Functional nanoliter chemical microarray for ultra high throughput screening and kinase profiling," Abstracts of Papers of the American Chemical Society 230, U2744-U2745 (2005).
K. Lo, W. S. Denney and S. L. Diamond, "Stochastic modeling of blood coagulation initiation," Pathophysiol.Haemost.Thromb. 34 (2-3), 80-90 (2005).
H. C. Ma et al., "Nanoliter homogenous ultra-high throughput screening microarray for lead discoveries and IC50 profiling," Assay and Drug Development Technologies 3 (2), 177-187 (2005).
A. Price et al., "Targeting viral-mediated transduction to the lung airway epithelium with the anti-inflammatory cationic lipid dexamethasone-spermine," Mol.Ther. 12 (3), 502-509 (2005).
G. Simmons et al., "Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry," Proc.Natl.Acad.Sci.U.S.A. 102 (33), 11876-11881 (2005).
G. Simmons et al., "Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry," Proc.Natl.Acad.Sci.U.S.A. 102 (33), 11876-11881 (2005).
S. L. Diamond, "High efficiency lipofection and gene correction of mouse embryonic stem cells using nuclear targeting technology." Abstracts of Papers of the American Chemical Society 227, U206-U206 (2004).
D. M. Eckmann and S. L. Diamond, "Surfactants attenuate gas embolism-induced thrombin production," Anesthesiology 100 (1), 77-84 (2004).
D. N. Gosalia, C. M. Salisbury and S. L. Diamond, "Profiling serine protease substrate specificity with solution phase peptide microarrays." Abstracts of Papers of the American Chemical Society 227, U204-U204 (2004).
J. A. Gruneich et al., "Cationic corticosteroid for nonviral gene delivery," Gene Ther. 11 (8), 668-674 (2004).
J. Y. Ji and S. L. Diamond, "Exogenous nitric oxide activates the endothelial glucocorticoid receptor," Biochem.Biophys.Res.Commun. 318 (1), 192-197 (2004).
K. E. Kadash, M. B. Lawrence and S. L. Diamond, "Neutrophil string formation: hydrodynamic thresholding and cellular deformation during cell collisions," Biophys.J. 86 (6), 4030-4039 (2004).
K. Lo and S. L. Diamond, "Blood coagulation kinetics: high throughput method for real-time reaction monitoring," Thromb.Haemost. 92 (4), 874-882 (2004).
H. Ma et al., "Mouse embryonic stem cells efficiently lipofected with nuclear localization peptide result in a high yield of chimeric mice and retain germline transmission potency," Methods 33 (2), 113-120 (2004).
Goel MS, Diamond SL.Factor VIIa-mediated tenase function on activated platelets under flow. J Thromb Haemost. 2004 Aug;2(8):1402-10.
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Dennis E. Discher
Professor of Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics; Physics and Cell & Molecular Biology Graduate Groups; Adjunct Professor, Structural Biology – The Wistar Institute; Member, Institute of Medicine and Engineering,Graduate Group Chair, Chemical and Biomolecular Engineering.
Email: discher at seas.upenn.edu
Personal Website | Research Website
Research Interests: Stem Cells and Nano/BioMolecular Science & Engineering are our main areas of interest. We pursue and exploit deeper understanding of protein & polymers aspects of membranes and soft interfaces within and across the fields of systems biophysics and materials. Systems and Processes of direct interest include: protein folding and flexibility, cell deformability and immunocompatability, block copolymer vesicles (Polymersomes) and worm-like micelles (Filomicelles) for drug delivery, physical determinants of stem cell and myocyte differentiation and disease, and nuclear envelope-chromatin interactions in isolated nuclei. Methods used range from molecular biology and single molecule AFM to micro-patterning and fluorescence ultra-microscopy. Modeling efforts range from pathway kinetics and continuum mechanics to computation intensive Monte Carlo and Molecular Dynamics.
Selected Recent Publications: C.P. Johnson, H-Y. Tang, C. Carag, D.W. Speicher, and D.E. Discher. Forced unfolding of proteins within cells. Science (Aug.3, 2007).
Y. Geng, P. Dalhaimer, S. Cai, R. Tsai, M. Tewari, T. Minko, and D.E. Discher. Shape effects of filaments versus spherical particles in flow and drug delivery. Nature Nanotechnology 2: 249-255 (2007).
P. Dalhaimer, D.E. Discher*, T. Lubensky. Crosslinked actin networks exhibit liquid crystal elastomer behavior, including soft-mode elasticity. Nature Physics 3: 354-360 (2007) (*corresponding author).
Engler, S. Sen, H.L. Sweeney, and D.E. Discher. Matrix elasticity directs stem cell lineage specification. Cell 126: 677-689 (2006).
F. Ahmed, R. Pakunlu, G. Srinivas, A. Brannon, F.S. Bates, M.L. Klein, T. Minko, and D.E. Discher. Shrinkage of a rapidly growing tumor by drug-loaded polymersomes: pH-triggered release through copolymer degradation. ACS - Molecular Pharmaceutics 3: 340-350 (2006).
D.E. Discher*, P. Janmey, Y-L. Wang. Tissue cells feel and respond to the stiffness of their substrate. Science 310: 1139-1143 (2005). (*corresponding author).
Y. Geng and D.E. Discher. Hydrolytic shortening of polycaprolactone-block-(polyethylene oxide) worm micelles. JACS - Journal of the American Chemical Society 127: 12780-12781 (2005).
V. Ortiz, S. Nielsen, M.L. Klein, and D.E. Discher. Unfolding a linker between helical repeats. Journal of Molecular Biology 349: 638-647 (2005).
A. Engler, M. Sheehan, S. Sen, C. Bonnemann, H.L. Sweeney, and D.E. Discher. Myotubes differentiate optimally on substrates with tissue-like stiffness: Pathological implications of stiff or soft microenvironments. Journal of Cell Biology 166(6): 877-887 (2004). ** With accompanying Editor's Highlight. And Highlight in Nature **
D.E. Discher* and A. Eisenberg. Polymer Vesicles. (invited Review) Science 297: 967-973 (2002). Cover Article (*corresponding author).
P. Carl, C. Kwok, G. Manderson, D.W. Speicher, and D.E. Discher. Forced unfolding modulated by disulfide bonds in the immunoglobulin domains of a cell adhesion molecule. PNAS (Proceedings of the National Academy of Science – USA) 98: 1565-1570 (2001).
H. Aranda-Espinoza, H. Bermudez, F.S. Bates, and D.E. Discher. Electromechanical limits of polymersomes. Physical Review Letters 87: 208301/pg.1-4 (2001).
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Eduardo D. Glandt
Dean, School of Engineering and Applied Science; Robert D. Bent Professor of Chemical and Biomolecular Engineering
Email: eglandt at seas.upenn.edu
Personal Website
Research Interests: Molecular simulations of gas adsorption, polymer adsorption, barriers to mass transfer in catalysts and adsorbents, modeling of industrially relevant adsorbents. Molecular Simulations of Gas Adsorption: This work applies molecular models and computer simulation techniques to investigate how the microstructure of a porous material affects its physical and chemical properties and, especially, its capacity as an adsorbent. The goal is to offer guidance in the preparation of high-capacity adsorbents. For example, adsorbed natural gas offers attractive features as a potential fuel for urban transportation: the filling pressure is relatively low (300-400 psig) compared to that of compressed gas, while the energy density may be as high as 20% of that for liquified natural gas. Important practical problems that affect the implementation of adsorption systems can be readily examined by molecular simulation. They include (i) heat effects, which severely limit the feasible rates of adsorption and desorption; (ii) multicomponent separation, which leads to a partial saturation of the substrate by traces of heavier components; and (iii) the presence of very active impurities, such as water vapor, which results in capillary condensation and pore blockage. Thermodynamics and Gelation of Polymer Solutions: Some powerful techniques developed for the molecular modeling of simple liquids, the so-called integral-equation theories, can now be extended to the much more challenging problem of describing the thermodynamics and structure of polymer solutions and melts. Our research program is a theoretical and experimental study of the formation of physical gels, such as those used in foods and similar applications. The "gelation phase diagram" is similar to but more complex than a thermodynamic phase diagram. This work is also concerned with the configuration and thermodynamic properties of polymer molecules in random porous media. Their distribution and retention are important in chromatographic separation processes as well as in oil-recovery applications. Transport Properties of Random Materials: The effective properties (e.g. diffusivity, thermal and electrical conductivities, permeability to fluid flow, and even chemical reacti
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