The Baker research group utilizes multidimensional separation techniques such as solid phase extractions (SPE), liquid chromatography (LC), ion mobility spectrometry (IMS), and mass spectrometry (MS) to evaluate molecules present and changing in biological and environmental systems. Research projects include the development of high-throughput analyses to study numerous samples in a short time period as well as informatics studies to evaluate and connect the complex multi-omic data with available phenotypic data.
Advanced Separations & Mass Spectrometry Methods
For both targeted and untargeted analyses, our lab utilizes multiple orthogonal methods of separation to resolve and identify components in a variety of complex matricies ranging from biological to environmental contexts. These methods include high performance liquid chromatography, super-critical fluid chromatography, rapid solid phase extractions, and ion mobility spectrometry coupled with high resolution mass spectrometry. As ion mobility is a gas phase separation method that occurs on the millisecond timescale, IMS is easily nested into other forms of chromatography to help separate and identify isomeric compounds in a shorter timescale. Currently, our work is mostly focused on glycomics, lipidomics, proteomics, and exposomics.
James’ work involves application of IMS-MS to the analysis of complex isomeric species in a variety of matrices. Specifically, James has applied IMS-MS to the rapid separation of polyfluoroalkyl substances (PFAS) in collaboration with the Knappe lab, as well as credentialed metabolomic samples in collaboration with the Patti lab.
Karen’s work focuses on examining the intricacies of molecular folding as it relates to biological function. Karen studies azapeptide conformers and corresponding modifications using IMS in collaboration with the Proulx lab. She also explores rapid separations for isoaspartic acid-containing peptides for biopharmaceutical applications.
Environmental & Clinical Research
One of the primary focuses of our lab is the analysis of molecules in environmental and biological systems, as well as the interaction between human health and the environment . Each lab member works on implementing ongoing advancements in ion mobility spectrometry-mass spectrometry methodology and data analysis for a variety of applications to meet these goals.
Melanie is working on elucidating lipid dysregulation in diseases such as Alzheimer’s disease, preeclampsia, gestational diabetes, type 2 diabetes and in instances of myocardial infraction. She is also working on understanding why patients within the same disease group develop different lipid profiles from factors such as age, diet and external environment and implementing additional omic analyses including proteomic, phenomics, genomics and metallomics.
Karen is working in collaboration with the Muddiman group to investigate the role of glycosylation in Alzheimer’s disease. This involves characterization of potential isomeric species of N-linked glycans in both healthy and diseased brain tissue using IMS-MS.
James and MaKayla are investigating how structural changes in PFAS composition can be detected in untargeted analyses using IMS, reverse phase chromatography, and mass defect analysis. Working with collaborators, we are developing methods to increase confidence in molecular identification of these persistent organic pollutants. On the other hand, Kaylie is investigating the downstream of PFAS exposure on biological pathways of vegetable and human systems using a multi-omics approach. She is also working on identifying lipid markers of differential responses following treatment for severe smoke inhalation.
Allison is working to increase annotation confidence and metabolite coverage in microbiome studies. She is also working on using IMS-MS to increase the coverage of isomeric bile acid species and identify new bile acid conjugates in collaboration with the Theriot lab.
Caitlin is working to identify contaminants released into a variety of drinks from plastic and paper straws.
While multidimensional experimental analyses, such as LC-IMS-MS/MS, provide specific molecular characterization and identification capabilities, annotation and interpretation of the data is severely limited by lack of software capabilities. For lipidomics data specifically, the biological interpretation of lipid data via pathway analysis requires the oversimplification of lipids to broader classes, rendering the insight from full lipid speciation irrelevant. We are working to develop comprehensive, high-throughput tools for lipid annotation, visualization and interpretation that overcome these challenges.
Kaylie is currently developing sample-specific spectral libraries within the free and open-source software Skyline for the rapid identification of diverse lipid species. By targeting LC, IMS, MS and MS/MS information, all lipids in the library are simultaneously annotated and visualized with a high degree of confidence. Allison is utilizing Skyline in a similar manner to rapidly characterize and confidently annotate bile acids and other metabolites of interest in microbiome studies.
Melanie is working with collaborators in the Fourches and Reif labs to relate lipid variability to structural and clinical information in biological contexts. Specifically, we are working on creating visualization techniques to relate lipids by their head group and fatty acyl composition through hierarchical clustering in R and further relating lipid structural composition to variables such as BMI, age and diet. These tools allow us to integrate biological variability to clinical and molecular information, thus improving our understanding of lipid variability.
Funding, Acknowledgements & Collaborations