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Lion fountain with blue skies on Kaufman Mall.

托马斯游标

tv-3

RESEARCH教授

电话: +1 757 683 7046

电子邮件: pvernier@guoyao100.net

地址: IRP 2, 4211 Monarch Way, Norfolk, VA, 23508

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Education

  • 博士: Electrical Engineering, University of Southern California, 2004
  • B.S.: 化学istry, 医学杂志ogy, Wheaton College, 1968


RESEARCH描述

Electric fields pervade biological systems, from the atomic interactions that determine the minimum free energy paths of ions through membrane channels to the transmission of signals through the nervous systems of multicellular animals. Every molecular link in the complex genomic, 转录组, 蛋白质组学, "pan-omic" web of a living organism is formed from the physical and chemical associations of atoms, 我们用牛顿力学来分析, 库仑定律的, 量子力学工具. And the consciousness which permits our contemplation of these matters is itself anchored in the electrical networks of the human brain.

肌肉收缩, 感觉, and dreams are all associated with and can be modified by electrical signals. Our knowledge of the mechanisms of the interactions between electric fields and cells, 器官, 和组织, 然而, 是有限和不完整的. At the most fundamental level electric fields generate forces on atoms and molecules — this is the regime of 纳米级生物电学. We concentrate on the effects of brief (nanosecond), intense (megavolt-per-meter) pulsed electric fields on cells 和组织, combining experimental observations with molecular simulations, in order to identify and understand the molecular-level interactions between external electromagnetic fields and biological structures and systems.

Ongoing experimental observations. Pulsed electric fields can induce transport of normally impermeant ions and small molecules across the cell membrane, a process called electroporation or electropermeabilization. This phenomenon is often studied with microscopic imaging to monitor changes in the intracellular concentration and distribution of fluorescent dyes, often reported in relative or arbitrary units. To produce truly quantitative measurements of electroporative transport, we use calibrated confocal microscopy to track the entry of small molecules into cells, and we correlate these observations with molecular dynamics simulations of transport through lipid electropores. Our results challenge the common assumption that small molecule transport through electropermeabilized membranes is dominated by simple diffusion through electropores.

分子建模. We perform molecular dynamics (MD) simulations of electropore formation in phospholipid bilayers to understand the nanoscale physics of electropermeabilization. Building on simple systems consisting of bilayers formed with a single kind of phospholipid and water, we are investigating now the effects of including in these systems ions (Na+, K+, Ca2+, Cl-), 胆固醇, and more complex mixtures of phospholipids and other components of biological membranes, including transmembrane peptides (simple membrane proteins).

Inflammasome激活. Experimental studies are currently underway to test the hypothesis that intense (MV/m), ultrashort (ns) electrical stimulation during electroblative therapy for solid tumors can perturb mitochondrial membranes, causing intracellular release of damage-associated molecular patterns (DAMPs) like oxidized mitochondrial DNA and cardiolipins in intact, 可行的细胞. The presence of these DAMPs in the cytoplasm activates inflammasomes, supramolecular platforms that initiate an innate immune response against the tumor.

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最相关的出版物

  1. 游标,P. T., Y. 太阳,我. Marcu,年代. 生活C. M. Craft和M. A. 甘德森. 2003. Calcium bursts induced by nanosecond electric pulses. 物化学. Biophys. Res. Commun. 310(2):286-295.
  2. 游标,P. T., Y. Sun和M. A. 甘德森. 2006. Nanoelectropulse-driven membrane perturbation and small molecule permeabilization. BMC Cell 医学杂志 7:37.
  3. 游标,P. T., M. J. 齐格勒,Y. 太阳,W. V. 常,M. A. 甘德森和D. P. 从事公务. 2006. Nanopore formation and phosphatidylserine externalization in a phospholipid bilayer at high transmembrane potential. J. Am. 化学. Soc. 128(19):6288-6289.
  4. 莱文,Z. A., P. T. 游标. 2010. Life cycle of an electropore: Field-dependent and field-independent steps in pore creation and annihilation. J. 会员. 医学杂志. 236(1):27-36.
  5. Tokman, M., J. H. 李,Z. A. 莱文,M. C. Ho米. E. Colvin和P. T. 游标. 2013. Electric field-driven water dipoles: Nanoscale architecture of electroporation. 《网上十大网赌娱乐大全》 8(4):e61111.
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