A5007199127- Metabolomics and Mass Spectrometry Studies
- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Proteomics Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Glycogen Storage Diseases and Myoclonus
- Mass Spectrometry Techniques and Applications
- Liver Disease Diagnosis and Treatment
- Immune cells in cancer
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Advanced NMR Techniques and Applications
- Diet and metabolism studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Atherosclerosis and Cardiovascular Diseases
- Lysosomal Storage Disorders Research
- Genetics and Neurodevelopmental Disorders
- Cancer, Hypoxia, and Metabolism
- Receptor Mechanisms and Signaling
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Digital Mental Health Interventions
- Neonatal Respiratory Health Research
- Gut microbiota and health
University of Florida
2023-2025
Florida College
2023-2024
University of Massachusetts Chan Medical School
2024
University of Kentucky
2020-2023
Nia Association
2022
ID Genomics (United States)
2022
The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response: two findings that may be intrinsically linked through the concept immunometabolism. Here, we combined bulk, single-cell, spatial transcriptomics cell-specific spatially resolved analyses in mice expressing human APOE to systematically address role across age, neuroinflammation, AD pathology. RNA sequencing (RNA-seq) highlighted immunometabolic changes APOE4 glial...
Abstract Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application high-dimensionality reduction/spatial clustering and histopathological annotation matrix datasets to assess tissue metabolic heterogeneity in human lung diseases. Using features identified from this pipeline, hypothesize that channeling between glycogen N-linked...
Microglia undergo two-stage activation in neurodegenerative diseases, known as disease-associated microglia (DAM). TREM2 mediates the DAM2 stage transition, but what regulates first DAM1 transition is unknown. We report that glucose dyshomeostasis inhibits and PKM2 plays a role. As tumors, was aberrantly elevated both male female human AD brains, unlike it expressed active tetramers, well among + surrounding plaques 5XFAD mice. snRNAseq analyses of without Pkm2 mice revealed significant...
N-linked protein glycosylation in the brain is an understudied facet of glucose utilization that impacts a myriad cellular processes including resting membrane potential, axon firing, and synaptic vesicle trafficking. Currently, spatial map glycans within normal Alzheimer's disease (AD) human does not exist. A comprehensive analysis glycome would improve our understanding energy metabolism, linking metabolism to signaling events perturbed during AD progression, could illuminate new...
MS-based metabolomics methods are powerful techniques to map the complex and interconnected metabolic pathways of heart; however, normalization metabolite abundance sample input in heart tissues remains a technical challenge. Herein, we describe an improved GC-MS-based workflow that uses insoluble protein-derived glutamate for metabolites within each includes amino acids reduce biological variation detect small changes. Moreover, glycogen is measured workflow. We applied this study...
N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution tissues; therefore, spatial analyses of these crucial to our understanding physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique enables situ detection analytes with distribution. This workflow details a MALDI-MSI protocol for the profiling from tissues following application enzyme MALDI...
Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen an increase in lactate production during conventional rapid resection preservation by liquid nitrogen. contrast, show that these postmortem changes are not observed with simultaneous animal sacrifice situ fixation focused, high-power microwave. We further employ microwave to define the mouse model streptozotocin-induced type 1 diabetes. Using...
ABSTRACT Metabolites, lipids, and glycans are fundamental biomolecules involved in complex biological systems. They metabolically channeled through a myriad of pathways molecular processes that define the physiology pathology an organism. Here, we present blueprint for simultaneous analysis spatial metabolome, lipidome, glycome from single tissue section using mass spectrometry imaging. Complimenting original experimental protocol, our workflow includes computational framework called Spatial...
Genome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the role liver-specific CPT1a on hepatic metabolism.
Summary The E4 allele of Apolipoprotein E ( APOE ) is associated with both metabolic dysfunction and a heightened pro-inflammatory response – two findings that may be intrinsically linked through the concept immunometabolism. Here, we combined bulk, single-cell, spatial transcriptomics cell-specific spatially resolved analyses to systematically address role across age, neuroinflammation, AD pathology. RNAseq highlighted immunometabolic changes APOE4 glial transcriptome, specifically in...
Abstract As demonstrated by increased hippocampal insulin receptor density following learning in animal models and decreased signaling, density, memory decline aging Alzheimer's diseases, numerous studies have emphasized the importance of processes. This has been further supported work showing that intranasal delivery can enhance alter cerebral blood flow, improve recall. Additionally, inhibition function or expression using molecular techniques associated with reduced learning. Here, we...
Abstract Parvalbumin-positive interneurons (PV-INs) regulate neuronal and circuit activity, their dysfunction is observed across neurological conditions, including traumatic brain injury (TBI), epilepsy, Alzheimer’s disease, schizophrenia. PV-INs are particularly vulnerable to cell loss, potentially due increased metabolic demands arising from uniquely high level of electrical which render them susceptible pressure. Here, we use single-nucleus RNA-sequencing (snRNAseq) data a rodent model...
Ewing sarcoma (EWS) is a malignant bone tumor or soft-tissue that mainly affects children, adolescents, and young adults. Approximately half of all patients with will at some point develop either recurrent metastatic disease, less than 20% such surviving long-term no new therapy in sight. Two clinical features EWS are the EWS-FLI1 fusion oncogene Periodic acid-Schiff (PAS) positive intracellular glycogen aggregates. While contribution to tumorigenesis epigenetics has been extensively...
Alzheimer’s Disease (AD) is characterized by increased inflammation and glucose utilization as detected FDG-PET. Using a new deuterium MRI method based on [D7]glucose tracer, we can image the brain of mouse model AD with in plane resolution approaching 1 mm. Mass spectrometry imaging same brains shows characteristic changes protein associated glycans that correlate well immunohistochemical staining for inflammation. We believe this research pipeline provide powerful insights into pathophysiology.
High-resolution spatial imaging is transforming our understanding of foundational biology. Spatial metabolomics an emerging field that enables the dissection complex metabolic landscape and heterogeneity from a thin tissue section. Currently, metabolism highlights remarkable complexity in two-dimensional space poised to be extended into three-dimensional world Here, we introduce MetaVision3D, novel pipeline driven by computer vision techniques for transformation serial 2D MALDI mass...
Genome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the impact by which liver-specific CPT1a deletion impacts hepatic metabolism.Six-to-eight-week old male female knockout (LKO) littermate controls were placed on a low-fat or high-fat diet (HFD; 60% kcal fat) for 15 weeks. Mice necropsied after 16 hour fast, tissues collected lipidomics, matrix-assisted laser...
ABSTRACT The brain metabolome directly connects to physiology and neuronal function. Brain glucose metabolism is highly heterogeneous among regions continues postmortem. Therefore, challenges remain capture an accurate snapshot of the physiological in healthy diseased rodent models. To overcome this barrier, we employ a high-power focused microwave for simultaneous euthanasia fixation mouse tissue preserve metabolite pools prior surgical removal dissection regions. We demonstrate exhaustion...