David F. J. Tees, Ph.D.

Associate Professor

Department of Physics & Astronomy
251A Clippinger, Ohio University
Athens, OH 45701
Office - 357A Clippinger: 740-593-1694
Lab - 367, 355 & 352 Clippinger: 740-593-1725
Fax: 740-593-0433
E-mail: tees@ohio.edu

Current Research

Research interests

Recruiting

I am recruiting for a graduate student and I am always interested in discussing summer projects with undergraduate students.

Projects and Interests

1. Mechanical properties of cancer cells as a biomarker for stemness

Metastasis is the process in which cancer cells separate from a primary tumor where they first develop and travel to other places in the body (usually using the blood circulatory system). This process is thought to be connected to cancer stem cells which are less differentiated than regular cancer cells and also proliferate more slowly. Cancer stem cells may have more potential for being metastatically invasive, however, and once they reach the new site somewhere else in the body, they can re-differentiate to cancer cells that divide faster thus and create a new tumor. A number of biochemical markers for cancer stem-cells have been proposed (they can be identified using marker antibodies and flow cytometry). We hypothesized that there may also be biophysical characteristics that make a cell more invasive (e.g. changes to cell stiffness or cell rheology) and that cancer stem cells may evolve some of the characteristics as they become functionally like white blood cells, which can also traffic into and out of the circulatory system.

We have used micropipette aspiration and particle-tracking microrheology to investigate stiffness and rheological differences between breast cancer cell lines with stem-like and non-stem-like phenotypes as determined by surface markers. We are also working to develop high-throughput microfluidic channel devices to measure mechanical properties. This work is being done in collaboration with Dr. Monica Burdick in the Russ College of Engineering. This work was supported by National Science Foundation grants CBET-1106118 and Major Research Instrumentation CBET-1039869.

2. Cell adhesion in micropipettes as a model for capillary adhesion

Capillaries are the smallest blood vessels in ones body. They are smaller, in fact, than some of the cells that have to go through them. Red blood cells (which carry oxygen) are very deformable and go through easily. White blood cells are stiffer and take some time to deform before they can can fit in. Under normal circumstances, a large fraction of one's white cells are in the lung due to the large number of small vessels there. During infection, that fraction can go up even higher, leading to a disappearance of white cells from the rest of the body. Exactly how white cells become pooled in the lung and other capillary beds is not clear. Some say that it is due to "mechanical trapping", although the exact physical basis of this trapping is not clear. Another possibility is that adhesive proteins act as a kind of glue to trap cells. This second mechanism is known to work in larger vessels, but there don't seem to be a lot of these adhesive proteins in capillaries. Our work will examine these two possible mechanisms and clarify the factors that are required for mechanical trapping and adhesive trapping. We hypothesize that both factors are important under the right circumstances.

We use small glass tubes (micropipettes) with a diameter in the same range as capillaries as a model system. We have developed techniques for making micropipettes with different diameters and different rates of tapering. We can look at cells moving inside relatively straight tubes (like in the straight segments of capillaries) or in tapering regions (like at the entrances to capillaries). We coat the insides of the micropipettes with adhesive proteins to study the effects of adhesive proteins on cell motion inside the tubes. We can study ways to make the cells stick or not stick as desired.

The ability to control adhesion of white cells is important in the treatment of infection and cardiovascular diseases. The long-term goal is to understand what needs to be done in order to either promote (in the case of insufficient white cell arrest) or stop (in the case of too aggressive immune response) white cell adhesion in capillary beds. The technique developed here can thus be used as a research tool to assess whether new drugs will do what they need to do.

This work was initially supported by an award from the American Heart Association (AHA - Ohio Valley Affiliate). It was then continued though a CAREER award (BES-0547165) from the National Science Foundation

3. Single molecule biophysics using force spectroscopy:

Receptor-ligand bonds are involved in fertilization, fetal development, blood vessel growth, blood clotting, cancer metastasis, inflammation, cell signaling and homeostatic physiology. Many receptor-ligand bonds, (especially those involved in cell adhesion) are designed to resist hydrodynamic or cytoskeletal applied forces. The behavior of bonds under applied load determines how cells will adhere in the circulation or migrate in tissue. The need to study the force dependence of bond reaction rates has led to the development of techniques (such as the microcantilever method) to apply picoNewton-level forces to single bonds.

Links to some useful materials about the cantilever system are given below. Some are rather large

For a PDF file of a tutorial on Single Molecule Forced Unbinding (given originally as a tutorial in March, 2004 at the American Physical Society meeting), click here.

Techniques & Equipment

Tees Lab Members

Current members:

Alumni (Graduate Students):

Alumni (Undergraduates):

How to get up to speed for graduate studies in the Tees lab:

If you have no previous biophysics training, please consider taking my course PHYS 5301 - Cell and Molecular Biophysics. You should also start attending the Biophysics Seminar (PHYS 8301) on Wednesday afternoons at 4:10 p.m. In order to get up to speed with the biological background you'll need, you should get a copy of Alberts et al.'s Molecular Biology of the Cell (it could be an older edition) and start reading at Chapter 1. For background on the specific projects, you should read the introductory chapters of theses and dissertations from lab alumni (see links above). You can then look at important references noted in those chapters to find important background papers and then find more recent relevant papers using Cited Reference searches in the ISI Web of Science. You should also start following the literature. Going through tables of contents for Biophysical Journal (which comes out every two weeks) and Proceedings of the National Academy of Sciences U.S.A. (which come out weekly) is a good place to start.