Analytical Sensors, Surface Chemistry, Array Fabrication, 3D Cell Culture Systems, Molecular Recognition, Protein-DNA interactions, Synthetic Biology
University of Pittsburgh, BS in Chemistry (2005); University of Wisconsin-Madison, PhD in Chemistry with Lloyd M. Smith (2009); Harvard University, Postdoctoral Fellow with George M. Whitesides (2010-2013)
We are interested in developing model systems, new materials, and new analytical tools to study reactions on surfaces, chemical and biological, and the behavior of enzymes and cells in tissue-like environments. Our research interests are broad, and thus we utilize a large number of analytical techniques to better understand the areas described below through precisely defined experiments and measurements.
We are interested in controlling the electronic and surface properties of carbon-based thin films through chemical functionalization. While there are a number attachment chemistries for carbon- and silicon-based substrates, the mechanism of attachment for many of these reactions is not known. Through a combination of infrared spectroscopy, X-ray and ultraviolet photoelectron spectroscopies, measurements of surface free energy, and gravimetric analysis we are elucidating these mechanisms.
The new surface chemistries we develop are used to prepare arrays of biomolecules, for example arrays of dsDNA to screen protein-DNA interactions and arrays of membrane proteins. We are particularly interested in determining how the presence of the substrate, and the surface chemistry that is tethering the molecules to the substrate, affects their stability and catalytic activity.
Membrane Proteins and Drug Metabolism
Cytochrome P450s are membrane-bound proteins that are responsible for metabolizing, or in some instances, activating, xenobiotics in the human body. There are a number of in vitro assays to screen xenobiotic metabolism that utilize variants of CYP450 enzymes that do not contain the membrane binding domain. It is currently not clear if the activity of these truncated enzymes is representative of full-length, membrane-bound CYP450s.
We are also developing surface chemistries to prepare arrays of membrane proteins. The goal of this project is an array in which we can screen and quantify the metabolism of a xenobiotic in the presence of a single CYP450 enzyme, or multiple CYP450s working in concert.
Membrane Cellular Persistence and Invasion
Communities of cells — whether they are the numerous species of bacteria that compose a biofilm, or the different cell types that compose human tissue — communicate through the formation of gradients of signaling molecules.
We are developing three-dimensional constructs to culture cells that are capable to quantifying the small- and bio-molecules comprising the cellular environment. There is a general consensus that the phenotype and behavior of cells is markedly different in two- and three-dimensional cultures, and we believe an assay that mimics the environment of mammalian cells in a tissue or bacterial cells in a biofilm will provide a more accurate picture of what factors cause cells to become mobile, for instance a tumorigenic cell, or dormant, for example a bacterial persister cell.