I am a 4th year PhD student in the laboratories of William Shih and Don Ingber at Harvard Medical School. I work at the Wyss Institute for Biologically Inspired Engineering.

three dimensional DNA origami

The Shih lab has pioneered 3-dimensional DNA origami, a molecular engineering technique that enables the self-assembly of billions of precisely defined particles at the nanometer scale.
We want to use the DNA origami method to design tiny nano machines that will not only rival nature's toolkit in its complexity, but will allow us to manipulate biological processes to cure diseases.

computer model projections and TEM images of 3D origami shapes (adapted from Douglas et al., 2009) - from left to right: monolith, square nut, railed bridge, slotted cross, stacked cross.

For my dissertation, I use DNA nano structures to build biomedical devices. Currently, I am exploring ways to use them (1) as cell delivery vehicles or (2) as templates for novel actuatable extracellular matrix materials.

cell delivery

Cellular uptake has been shown to be dependend on particle shape and size. For example, a small rod-like particle - shaped much like a common bacterium - is taken up by cells more easily than spherical particles or very long tubes. The exquisite spatial precision of our DNA nanostructures allows us to probe the shape space of particle uptake in unprecedented detail. My preliminary studies indicate that DNA nanotubes 400 nm in length and 6 nm in diameter have much poorer entry than when the same nanotubes are bent onto themselves to form 60 nm DNA rings. Together with a PostDoc in the lab, I am continuing to explore many more permutations of these shapes to improve their cell entry characteristics. Finding the optimal particle shape that facilitates cell entry will help us design better cell delivery vehicles for targeted drug and gene delivery therapies.

actuatable matrix materials

The mechanical properties of the extracellular environment plays an important role in directing and manifesting cell behavior. In addition, it is known that a tissue becomes progressively stiffer during neoplastic development and that tumor tissue in general is much stiffer than normal tissue. One way to address cancer might therefore be to revert the mechanical properties of the tumor environment. Together with another graduate student, I am developing matrix materials that we will be able to actuate on demand. Using a mixture of DNA nanotubes and extra-cellular matrix proteins as the basic building units and light-sensitive DNA duplexes as cross-linkers, will allow us to increase or decrease the compliance of the matrix gels in response to either visible or UV light. We hope that these studies will enable us to switch the mechanical properties of our DNA-protein substrates and ultimately reprogram cancer cells to become healthy tissue.
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