Mass spectrometry: Low-flow electrospray ionization, biomarker identification, metabolomics, proteomics, molecular imaging mass spectrometry, tandem mass spectrometry.
High resolution mass spectrometry; tandem mass spectrometry; metabolomics; imaging mass spectrometry, low-flow microreactors.
The general objective of our research is to obtain structural information of molecules with electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) relevant to processes in the life sciences. En route to achieving this broad goal, we have developed miniaturized approaches for electrospray ionization (nanospray) and sample preparation protocols for MALDI.
Metabolomics and mass spectrometry. Our group is using mass spectrometry approaches to discover and validate biomarkers which are implicated in autism. This involves screening of human urine samples and developing quantitative approaches (using isotopic labeling or other chemical labeling) to determine levels of specific metabolites, including the tetrapyrrole stercobilin and the redox modulator peptide glutathione. The approaches are also being extended to screening fecal material excreted from transgenic mice used as a rodent model of autism. In addition, because of the high mass accuracy capability of the Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, we can deduce molecular compositions and (with MS/MS) structures of unknown metabolites. Additional metabolomics research in our group is focused on metabolites found in soybeans.
Imaging Mass Spectrometry, IMS). Using MALDI, it is possible to interrogate the surfaces of tissues (animal and plant) and examine their spatial distribution and even three-dimensional distribution. Our group is developing two-dimensional sheets to help improve the spatial resolution of imaging MALDI mass spectrometry and to extend it to less polar analytes than those currently accessible with traditional MALDI matrixes. Applications of MALDI imaging in our laboratory include distribution of substances delivered directly to mouse brains, distribution of molecules throughout the brains of mouse models of autism, and in plant metabolomics, with a focus on examination of how the aging of a plant leaf throughout a season can be tracked via IMS.
Low-flow microreactors. Our group has made significant contributions in the development of miniaturized emitters for low-flow electrospray ionization. Our focus has turned to coupling such devices with enzyme microreactors for extremely rapid proteolysis and proteomic analysis. Such microreactors are stable for a period of months. We couple these devices with high-resolution FT-ICR for unparalleled analysis of proteolytic peptides and higher-order structural analysis combined with hydrogen-deuterium exchange (HDX).