David B Hill, PhD

Research Biosketch Links Contact

Research Focus

Hill

The primary interest of my research is Mucociliary clearance and how it is affected by diseases such as Cystic Fibrosis and Chronic Sinusitis.

During normal respiration, thousands of bacteria and other airborne irritants are inhaled every hour. Despite this constant intake of pathogens, the body is able to maintain sterility in the airways below the larynx. The task of accomplishing this feat falls to the protect airway surface liquid layer, a two-phase liquid consisting of a viscoelastic mucus layer as well as the periciliary liquid layer through which cilia beat, clearing mucus from the airways. In diseases such as cystic fibrosis, the mucus layer becomes increasing solid-like, leading to a decrease in mucus clearance as well as an increased rate of infection. In order to understand the phenomena of mucociliary clearance, it is necessary to understand the physical properties of the mucus layer as well as the driving forces that propel the fluid: the pressure gradient consistent with normal tidal breathing and the forces imparted on the mucus layer by cilia. It is the goal of my research to characterized and model the airway surface liquid in terms of its physical properties, chemical composition, flow, and response to pathogenic material.

Current Research Projects

  • Mucus Rheology: Employing the techniques of microbead rheology, cone and plate, and driven magnetic bead rheology, the goal of this project is to determine the physical properties of mucus so that the fluid can be successfully modeled
  • Three Dimensional Force Microscope (3DFM): The 3DFM allow us to evaluate the viscoelastic modulus of fluids to viscous to be studied with Microbead Rheology, apply forces directly to biological systems (CF Mucus, ActA, and beating cilia), and map the topography of entangled mess networks often found in viscoelastic fluids
  • Cilia induced Stress-Strain in Mucus: The motion of tracer particles is examined to determine the amount of deformation imposed on mucus by cilia and examine how the deformation is propagated thru the fluid.
  • Modeling mucus flow and small molecule diffusion: Experimental results are used to determine the correct constitutive laws to model and predict small molecule diffusion and mucus flow.
  • Micro-Parallel Plate Rheometer (MPPR): The MPPR is an optically based rheometer that determines the bulk viscoelastic properties of fluids using quintiles less than 10uL.

Previous Research Projects

  • Polarization-Modulate Differential Interference Contrast Microscopy
  • Digital Image Processing
  • Magnetic Design / Manipulation of Magnetic Beads

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Biographical Sketch

David B Hill, PhD, Research Associate

Education

PhD, Physics; Wake Forest University, July 2003. Dissertation: Measuring the Work of Motor Proteins in PC12 Neurites
Advisor: George Holzwarth.
BS; Physics; Stetson University, May 1998.

Professional Experience

Research: Graduate Dean’s Fellow; Wake Forest University, June 1998 – July 2003.
Post Doctorial Fellow, Department of Physics and Astronomy, UNC Chapel Hill, July 2003 – March 2006.
Research Associate: Cystic Fibrosis Center, UNC Chapel Hill, March 2006 – Present.

Selected Publications

Please see links from the Pubmed feed in the righthand column for a more exhaustive list.

2010 Fallesen, T., D. HIll, et al. "Magnet polepiece design for uniform magnetic force on superparamagnetic beads" Review of Scientific Instruments Accepted.

2010 Hill, D. B., B. Lindley, et al. "The Micro-Parallel Plate Rheometer." Journal of Non-Newtonian Fluid Mechanics Preprint.

2010 Hill, D. B., V. Swaminathan, et al. "Force Generation and Dynamics of Individual Cilia under External Loading." Biophysical Journal 98 (1): 57-66.

2009 Lindley, B., E. Howell, et al. "Stress Communication and Filtering of Viscoelastic Layers in Oscillatory Shear." Journal of Non-Newtonian Fluid Mechanics 156: 112-120.

2008 Hill, D. B., J. C. Macaosko, et al. "Motion-enhanced, differential interference contrast (MEDIC) microscopy of moving vesicles in live cells: VE-DIC updated." Journal of Microscopy-Oxford 231 (3): 433-439.

2008 Mitran, S. M., M. G. Forest, et al. "Extensions of the Ferry shear wave model for active linear and nonlinear microrheology." Journal of Non-Newtonian Fluid Mechanics 154 (2-3): 120-135.

2006 Matsui, H., V. E. Wagner, et al. "A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms." Proc Natl Acad Sci U S A 103 (48): 18131-6.

2004 Hill, D. B., M. J. Plaza, et al. "Fast vesicle transport in PC12 neurites: velocities and forces." European Biophysics Journal with Biophysics Letters 33 (7): 623-632.

2002 Holzwarth, G., K. Bonin, et al. "Forces required of kinesin during processive transport through cytoplasm." Biophysical Journal 82 (4): 1784-1790.

2000 Holzwarth, G. M., D. B. Hill, et al. "Polarization-modulated differential-interference contrast microscopy with a variable retarder." Applied Optics 39 (34): 6288-6294.

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Links

The Virtual Lung Project

Computer Integrated Systems for Microscopy and Manipulation

http://www.unc.edu/~dbhill/

Contact Information

4021 Thurston-Bowles Bldg.
The University of North Carolina at Chapel Hill
Campus Box #7248
Chapel Hill, NC 27599
Phone: (919) 843.2577
Fax: (919) 966.7524
Email: dbhill@email.unc.edu

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