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Systems Biology of Angiogenesis
Angiogenesis (the growth of new blood vessels) is important in such diverse areas as cancer, cardiovascular disease, arthritis, diabetes, wound healing, and tissue engineering. We are interested in quantitative understanding of the mechanisms of microvascular network formation under different conditions. Using methods of computational and mathematical biology, we analyze the signaling pathways leading to angiogenesis, and the cellular mechanisms governing tubulogenesis and network formation. Our current focus is on Vascular Endothelial Growth Factor (VEGF) and its interactions with endothelial cell receptors, Matrix Metalloproteinases (MMPs) and their role in the extracellular matrix proteolysis and release of growth factors, and a transcription factor Hypoxia Inducible Factor HIF-1alpha; we are constructing multiscale models of angiogenesis spanning several levels of biological organization. In vitro experiments using endothelial cell assays are also conducted in our laboratory.
Blood Flow and Molecular Transport in the Microcirculation
We are formulating computational models of the microcirculation based on anatomical, biophysical, and physiological experimental data, spanning from the molecular to the tissue levels. These include detailed models of microcirculatory blood flow and molecular transport (e.g., oxygen and nitric oxide) and their regulation, and creation of databases of parameters necessary for models input and validation.
Electromechanical Transduction in the Cochlear Outer Hair Cell
Outer hair cell are among the most sensitive mechanosensory cells in the body and they are crucial for the amplification, sharp frequency selectivity, and nonlinearities of the mammalian cochlea. These cells perform exquisite electromechanical transduction at acoustic frequencies and exhibit a unique form of cell motility. The motility is attributed to membrane-based molecular motors driven by changes in the transmembrane potential. We develop biophysically-based computational models of cell mechanics, molecular transport, and cell electromotility at the microscopic and nanoscopic (molecular) scales.
Send questions to apopel@jhu.edu
Updated 10/08/2007
SELECTED PUBLICATIONS
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Systems Biology of Angiogenesis
F.M. Gabhann, A.S. Popel. Interactions of VEGF isoforms with VEGFR-1, VEGFR-2, and neuropilin in vivo: a computational model of human skeletal muscle. Am. J. Physiol. Heart. Circ. Physiol. 292: H459-H474, 2007. [Abstract], [Full Text (pdf)]
F. Mac Gabhann, J.W. Ji, A.S. Popel. VEGF gradients, receptor activation, and sprout guidance in resting and exercising skeletal muscle. J. Appl. Physiol. 102: 722-734, 2007. [Abstract], [Full Text (pdf)]
F. Mac Gabhann, A.S. Popel. Targeting Neuropilin-1 to Inhibit VEGF Signaling in Cancer: Comparison of Therapeutic Approaches. PLoS Comp. Biol. 2: 1649-1662, 2006. [Abstract], [Full Text (pdf)]
F. Mac Gabhann, J.W. Ji, A.S. Popel. Computational model of vascular endothelial growth factor spatial distribution in muscle and pro-angiogenic cell therapy. PLoS Comp. Biol. 2: 1107-1120, 2006. [Abstract], [Full Text (pdf)]
A.A. Qutub, A.S. Popel. A computational model of intracellular oxygen
sensing by hypoxia-inducible factor HIF1 alpha.
J. Cell. Sci. 119: 3467-80, 2006. [Abstract],
[Full Text (pdf)]
J.W. Ji, N.M. Tsoukias, D. Goldman, and A.S. Popel. A computational model of oxygen transport in skeletal muscle for sprouting and splitting modes of angiogenesis. J. Theor. Biol. 241: 94-108. [Abstract], [Full Text (pdf)]
E.D. Karagiannis and A.S. Popel. Distinct modes of collagen type I proteolysis by matrix metalloproteinase (MMP) 2 and membrane type I MMP during the migration of a tip endothelial cell: Insights from a computational model. J. Theor. Biol., 238: 124-45, 2006. [Abstract], [Full Text (pdf)]
F. Mac Gabhann, M.T. Yang, A.S. Popel. Monte Carlo simulations of VEGF binding to cell surface receptors in vitro. Biochimica et Biophysica Acta - Molecular Cell Research, 1746: 95-107, 2005. [Abstract], [Full Text (pdf)]
F.
Mac Gabhann and A.S. Popel. Differential binding of VEGF isoforms to
VEGF Receptor 2 in the presence of Neuropilin-1: a computational model.
Am. J. Physiol. (Heart Circ. Physiol.). 288(6): H2851-60, 2005. [Abstract],
[Full
Text (pdf)]
R.J. Filion and A.S. Popel. Intracoronary administration of FGF-2: a computational model of myocardial deposition and retention. Am. J. Physiol. (Heart Circ. Physiol.), 288: H263-279, 2005. [Abstract], [Full Text (pdf)]
E.D. Karagiannis and A. S. Popel. A theoretical model of type I collagen proteolysis by matrix metalloproteinase (MMP) 2 and membrane type 1 MMP in the presence of tissue inhibitor of metalloproteinase 2. J. Biol. Chem. 279: 39105-39114, 2004. [Abstract], [Full Text (pdf)]
F. Mac Gabhann and A.S.
Popel. Model of competitive binding of vascular endothelial growth
factor and placental growth factor to VEGF receptors on endothelial cells. Am.
J. Physiol. (Heart Circ. Physiol.), 286: H153-164, 2004. [Abstract],
[Full
Text (pdf)]
Blood Flow and Molecular Transport in the Microcirculation
B. Chung, P.C. Johnson, A.S. Popel. Application of Chimera grid to modelling cell motion and aggregation in a narrow tube. Int. J. Numer. Meth. Fluids 53: 105-128, 2007. [Abstract], [Full Text (pdf)]
K. Chen, A.S. Popel. Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells. Free Radic. Biol. Med. 41: 668-680, 2006. [Abstract], [Full Text (pdf)]
S. Kim, A.S. Popel, M. Intaglietta, and P.C. Johnson. Effect of erythrocyte aggregation at normal human levels on functional capillary density in rat spinotrapezius muscle. Am. J. Physiol. Heart Circ. Physiol. 290: H941-H947, 2006. [Abstract], [Full Text (pdf)]
M. Kavdia and A.S. Popel. Venular endothelium derived NO can affect paired arteriole: a computational model. Am. J. Physiol. Heart Circ. Physiol. 290: H716-723, 2006. [Abstract], [Full Text (pdf)]
P. Bagchi, P.C. Johnson, and A.S. Popel. Computational fluid dynamic simulation of aggregation of deformable cells in a shear flow. J. Biomech. Eng., 127:1070-1080, 2005. [Abstract], [Full Text (pdf)]
A.S. Popel. Mathematical and Computational Models of the Microcirculation. In: Microvascular Research: Biology and Pathology. D. Shepro, Editor-in-Chief; P.A. D'Amore, C.M. Black, J.G.N. Garcia, D.N. Granger, C. Haudenschild, H.B. Hechtman, R.K. Jain, and J.A. Madri, Editors, Chapter 164, pp.1123-1129, Elsevier, New York, 2005.
A.S. Popel and P.C. Johnson. Microcirculation and
hemorheology. Ann. Rev. Fluid Mechanics,
37:43-69, 2005. [Full
Text (pdf)]
S. Kim, A.S. Popel, M. Intaglietta, and P.C. Johnson. Aggregate formation of erythrocytes in postcapillary venules. Am. J. Physiol. (Heart Circ. Physiol.), 288:H584-90, 2005. [Abstract], [Full Text (pdf)]
N.M. Tsoukias, M. Kavdia, and A.S. Popel. A theoretical model of nitric oxide transport in arterioles: Frequency vs amplitude dependent control of cGMP production. Am. J. Physiol. (Heart Circ. Physiol.), 286:H1043-H1056, 2004. [Abstract], [Full Text (pdf)]
M. Kavdia and A.S. Popel.
Contribution of nNOS and eNOS derived NO to microvascular smooth muscle NO
exposure. J. Appl. Physiol., 97:293-301, 2004. [Abstract],
[Full
Text (pdf)]
Electromechanical Transduction in the Cochlear Outer Hair Cell
D.R. Murdock, S.A. Ermilov, A.A. Spector, A.S. Popel, W.E. Brownell, and B. Anvari. Effects of chlorpromazine on mechanical properties of the outer hair cell plasma membrane. Biophys. J. 89:4090-4095, 2005. [Abstract], [Full Text (pdf)]
Z. Liao, A.S. Popel, W.E. Brownell, and A.A. Spector. Effect of voltage-dependent membrane properties on active force generation in cochlear outer hair cell. J. Acoust. Soc. Am. 118: 3737-3746, 2005. [Abstract], [Full Text (pdf)]
A.A. Spector,
A.S. Popel, R.A. Eatock, and W.E. Brownell. Mechanosensitive channels in the
lateral wall can enhance the cochlear outer hair cell frequency response. Ann. Biomed. Eng.
33:991-1002, 2005. [Abstract],
[Full Text (pdf)]
Z. Liao, A.S.
Popel, W.E. Brownell, and A.A. Spector. High-frequency force generation in the
constrained cochlear outer hair cell: A model study. J. Assoc. Res. Otolaryngol. (JARO),
6: 378-389, 2005. [Abstract],
[Full Text (pdf)]
Z.
Liao, A.S. Popel, W.E. Brownell, and A.A. Spector. Modeling high-frequency electromotility of cochlear outer hair cell in microchamber experiment. J. Acoust. Soc. Am.
117: 2147-2157, 2005. [Abstract],
[Full
Text (pdf)]