We use a variety of label-free imaging methods, among them coherent Raman and nonlinear fluorescence, to quantify molecular and mechanical heterogeneity of objects. We aim to exploit the unique capabilities of nonlinear optical imaging in our lab: unprecedented chemical specificity, high spatial, and high temporal resolution with minimal photo-damage, to gain new insight about local chemical heterogeneity in biology and disease.
We apply these techniques to study biophysics and chemistry of disease in three different areas:
1) lipid chemistry in oxidative and adipose tissues as related to obesity,
2) granule formation in relation to neurodegeneration, and
3) mechano-chemical control of structure and function in biomaterials.
In short, we engineer the tools to figure out why (and how) Nature engineered the molecules.
Mechano-chemistry in biomaterial networks
Bioamterials, particularly the extracellular matrix (ECM), hosts cells in the body. Cells and the ECM have a reciprocal relationship where they each influence one another, both via biochemistry and biomechanically. In this project, we investigate how mechanical inputs to proteinacious ECM and networks is coupled to molecular transitions in the constituent molecules. Moreover, what happens to downstream biochemistry, or even cell phenotype (e.g. invasiveness) in response to the molecular changes?
Liquid-liquid phase separation in cells
Liquid-liquid phase separation (LLPS) is a classical thermodynamic phenomenon that can be easily recreated by watching oil and vinegar as salad dressing, and it appears all over biology - in normal and pathological conditions. The goal of this topic is to explore how the molecular interactions between proteins and nuclei acids underlie their LLPS in cells? What is the structure of the macromolecules in the LLPS assemblies? Are the molecular structure dynamic? Which parts of the proteins are "sticky"?
Lipid chemistry in health and disease
Lipids are critical component of the cells and tissue, as the basic molecules in barriers to cellular entry, and also as the barrier for many (but not all!) intracellular compartments. In addition, these molecules are packaged into lipid droplets (LDs) that are incredibly dense energy stores. Interestingly the metabolic function of these LDs is only beginning to come to light; however, signficant research in the last decade has hinted toward a substantial impact of LDs in pathological transformation in diabetes, liver disease, and neurodegeneration. We are developing tools to quantify lipid chemsitry and morphology in situ.
Microscopy instrumentation and image processing
Super resolution microscopy (and the chemistry that made it possible) is arguably the most fundamental breakthrough in microscopy technology of our era by allowing scientists to overcome the Abbe resolution limit. Our efforts here are to try to improve contrast and resolution of chemical microscopy. In concert with that, we are trying to find ways to focus on what is "important" (subjective term, but the point is clear) in the data deluge that our tools produce using machine learning.