@article{pace_angel_drake_muddiman_2022, title={Mass Spectrometry Imaging of N-Linked Glycans in a Formalin-Fixed Paraffin-Embedded Human Prostate by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization}, volume={21}, ISSN={["1535-3907"]}, DOI={10.1021/acs.jproteome.1c00822}, abstractNote={N-Linked glycans are structurally diverse polysaccharides that represent significant biological relevance due to their involvement in disease progression and cancer. Due to their complex nature, N-linked glycans pose many analytical challenges requiring the continued development of analytical technologies. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a hybrid ionization technique commonly used for mass spectrometry imaging (MSI) applications. Previous work demonstrated IR-MALDESI to significantly preserve sialic acid containing N-linked glycans that otherwise require chemical derivatization prior to detection. Here, we demonstrate the first analysis of N-linked glycans in situ by IR-MALDESI MSI. A formalin-fixed paraffin-embedded human prostate tissue was analyzed in negative ionization mode after tissue washing, antigen retrieval, and pneumatic application of PNGase F for enzymatic digestion of N-linked glycans. Fifty-three N-linked glycans were confidently identified in the prostate sample where more than 60% contained sialic acid residues. This work demonstrates the first steps in N-linked glycan imaging of biological tissues by IR-MALDESI MSI. Raw data files are available in MassIVE (identifier: MSV000088414).}, number={1}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Pace, Crystal L. and Angel, Peggi M. and Drake, Richard R. and Muddiman, David C.}, year={2022}, month={Jan}, pages={243–249} }
 @article{pace_simmons_kelly_muddiman_2022, title={Multimodal Mass Spectrometry Imaging of Rat Brain Using IR-MALDESI and NanoPOTS-LC-MS/MS}, volume={21}, ISSN={["1535-3907"]}, DOI={10.1021/acs.jproteome.1c00641}, abstractNote={Multimodal mass spectrometry imaging (MSI) is a critical technique used for deeply investigating biological systems by combining multiple MSI platforms in order to gain the maximum molecular information about a sample that would otherwise be limited by a single analytical technique. The aim of this work was to create a multimodal MSI approach that measures metabolomic and proteomic data from a single biological organ by combining infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) for metabolomic MSI and nanodroplet processing in one pot for trace samples (nanoPOTS) LC-MS/MS for spatially resolved proteome profiling. Adjacent tissue sections of rat brain were analyzed by each platform, and each data set was individually analyzed using previously optimized workflows. IR-MALDESI data sets were annotated by accurate mass and spectral accuracy using HMDB, METLIN, and LipidMaps databases, while nanoPOTS-LC-MS/MS data sets were searched against the rat proteome using the Sequest HT algorithm and filtered with a 1% FDR. The combined data revealed complementary molecular profiles distinguishing the corpus callosum against other sampled regions of the brain. A multiomic pathway integration showed a strong correlation between the two data sets when comparing average abundances of metabolites and corresponding enzymes in each brain region. This work demonstrates the first steps in the creation of a multimodal MSI technique that combines two highly sensitive and complementary imaging platforms. Raw data files are available in METASPACE (https://metaspace2020.eu/project/pace-2021) and MassIVE (identifier: MSV000088211).}, number={3}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Pace, Crystal L. and Simmons, Jared and Kelly, Ryan T. and Muddiman, David C.}, year={2022}, month={Mar}, pages={713–720} }
 @article{pace_horman_patisaul_muddiman_2020, title={Analysis of neurotransmitters in rat placenta exposed to flame retardants using IR-MALDESI mass spectrometry imaging}, volume={412}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-020-02626-4}, abstractNote={Chemical exposures can adversely impact fetal development. For many compounds, including common flame retardants, the mechanisms by which this occurs remain unclear, but emerging evidence suggests that disruption at the level of the placenta may play a role. Understanding how the placenta might be vulnerable to chemical exposures is challenging due to its complex structure. The primary objective of this study was to develop a method for detecting placental neurotransmitters and related metabolites without chemical derivatization so changes in the abundance and spatial distribution of neurotransmitters in rat placenta following chemical exposure could be determined using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging. Without chemical derivatization, 49 neurotransmitters and their related metabolites were putatively identified in untreated rat placenta sections using mass measurement accuracy and spectral accuracy. A few neurotransmitters were less abundant in placentas that were exposed to various flame retardants and were further investigated by KEGG metabolic pathway analysis. Many of these downregulated neurotransmitters shared the same enzyme responsible for metabolism, aromaticl-amino acid decarboxylase, suggesting a mechanistic role. These data constitute a new approach that could help identify novel mechanisms of toxicity in complex tissues. Graphical abstract.}, number={15}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Pace, Crystal L. and Horman, Brian and Patisaul, Heather and Muddiman, David C.}, year={2020}, month={Jun}, pages={3745–3752} }
 @article{pace_muddiman_2020, title={Direct Analysis of Native N-Linked Glycans by IR-MALDESI}, volume={31}, ISSN={["1879-1123"]}, DOI={10.1021/jasms.0c00176}, abstractNote={Glycan analysis by mass spectrometry has rapidly progressed due to the role of glycans in disease and tumor progression. Glycans are complex molecules that pose analytical challenges due to their isomeric compositions, labile character, and ionization preferences. This study sought to demonstrate infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) as a novel approach for the direct analysis of N-linked glycans. The glycoprotein bovine fetuin was chosen for this analysis as its glycome is well characterized and heavily composed of sialylated glycans. Native N-linked glycans produced by enzymatic cleavage (via PNGase F) of bovine fetuin were analyzed directly by IR-MALDESI in both positive and negative ionization mode. In this study, we detected 11 N-linked glycans in negative mode and 4 N-linked glycans in positive mode, a significant increase in the amount of underivatized glycans detected by other ionization sources. Importantly, all N-linked glycans detected contained at least one sialic acid residue which are known to be labile. This work represents a critical first step for N-linked glycan analysis by IR-MALDESI with future efforts directed at mass spectrometry imaging.}, number={8}, journal={JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY}, author={Pace, Crystal L. and Muddiman, David C.}, year={2020}, month={Aug}, pages={1759–1762} }
 @article{bagley_pace_ekelof_muddiman_2020, title={Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging analysis of endogenous metabolites in cherry tomatoes}, volume={145}, ISSN={["1364-5528"]}, DOI={10.1039/d0an00818d}, abstractNote={We report the spatially resolved metabolic profiling of cherry tomatoes using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI); an ambient mass spectrometry imaging (MSI) technique that requires no sample derivatization.}, number={16}, journal={ANALYST}, author={Bagley, M. Caleb and Pace, Crystal L. and Ekelof, Mans and Muddiman, David C.}, year={2020}, month={Aug}, pages={5516–5523} }