About

Dr. Matthew S. Gentry is Professor and Chair of Biochemistry & Molecular Biology in the College of Medicine at the University of Florida. He is a prominent brain metabolism scientist with nearly 20 years of experience working on glycogen storage diseases (GSD). His research has made seminal discoveries in brain glycogen and glucose metabolism, and how perturbations in these pathways impact neuro-centric diseases. Dr. Gentry's work on Lafora disease, a childhood dementia and progressive myoclonic epilepsy caused by mutations in the genes encoding laforin or malin, has defined the biochemical properties of these genes, their functions in vivo, and developed therapeutic platforms including small molecules, anti-sense oligonucleotides, and antibody-enzyme fusions. His lab has established methodologies to assess pathogenic polyglucosan bodies, and his therapeutic approaches have progressed toward clinical trials, with some therapies successfully completing Phase I testing. Additionally, his research extends to Alzheimer's disease, Ewing sarcoma, lung cancer, and other neurodegenerative and metabolic disorders, focusing on defining disease mechanisms, developing pre-clinical drugs, and establishing clinical biomarkers. Dr. Gentry has been continuously funded by NIH since 2007, holds multiple patents, and has published over 100 scientific papers. He also directs the NIH-established Lafora Epilepsy Cure Initiative (LECI), a global consortium dedicated to understanding and treating Lafora disease.

Research topics

• Chemistry
• Biochemistry
• Biology
• Cell biology
• Internal medicine
• Immunology
• Neuroscience
• Endocrinology
• Medicine

Selected publications

• Peripheral amylin modulation rebalances brain glycolysis and Tau-Ser214 phosphorylation via cAMP-PKA signaling

  iScience · 2026-02-26

  articleOpen access

  . Together, these results define prediabetic hyperamylinemia as an upstream, modifiable driver of PKA-mediated tau pathology linking metabolic dysfunction to AD.

  PublisherDOI

• Mapping glycogen accumulation and treatment effect in Pompe disease with saturation transfer MRI

  Translational research · 2026-02-19

  articleOpen access

  Pompe disease is a glycogen storage disease caused by the impaired breakdown of glycogen in lysosomes, leading to abnormal glycogen accumulation in tissue. Here we use glycogen nuclear Overhauser effect (glycoNOE) MRI to detect glycogen levels in skeletal muscle in a mouse model of Pompe disease. Moreover, we evaluated if glycoNOE MRI could detect changes in glycogen load after enzyme replacement therapy. The results show that glycoNOE MRI can distinguish between Pompe mice and wildtype controls. Furthermore, the technique detected treatment-dependent changes in muscle glycoNOE signals, which were validated with ex vivo biochemical assays. To demonstrate potential human translation, glycoNOE MRI was applied to two Pompe patients and revealed elevated glycogen levels in patients compared to healthy controls.

  PublisherDOI

• Metabolic targeting of pantothenate by medium chain fats in glioblastoma cells

  Figshare · 2026-04-07

  otherOpen access

  Abstract Ketogenic diets are commonly used for epilepsy therapy and are increasingly being considered in cancer treatment, where metabolic reprogramming triggered by glucose restriction and ketosis alters energy provision as the therapeutic mechanism. However, a recently developed medium chain triglyceride product, with a high decanoic acid (DA) to octanoic acid (OA) ratio (DA: OA) has enabled a much less restrictive diet and is clinically effective as an epilepsy treatment, yet no studies have explored the product in cancer models. Here we investigate metabolic mechanisms of DA, OA and DA: OA using a cellular glioblastoma model, focusing on changes in energy metabolism. We show, at a transcriptional level, that DA provides the dominant regulatory influence, enhancing transcription of fatty acid and amino acid metabolism pathways, while reducing cancer-associated glucose metabolism and kinase pathways. DA: OA treatment shared some of these effects, with little influence from OA. At a protein level, DA: OA treatment played the dominant role, regulating metabolic, cancer and signalling pathways, including a large network centred around albumin and protein kinase activities. Finally, at a metabolomic level, both DA and DA: OA treatment reduced vitamin B5 (pantothenate) levels, which is necessary for the synthesis of coenzyme A used in the activation of fatty acids for energy provision, suggesting a novel mechanism to reduce cellular energy provision in cancer. Importantly, these effects occur under high glucose conditions. Thus, we show that decanoic acid-rich treatments may regulate glioblastoma cell biology through targeted effects on glucose and fatty acid metabolism and kinase signalling and may trigger a potential reduction in pantothenate levels in glioblastoma cells, providing a potential novel therapeutic mechanism in cancer treatment.

  PublisherDOI

• Epm2bP71A and Epm2bD148N knock-in mouse models of Lafora disease exhibit distinct and pronounced neurological alterations

  Progress in Neurobiology · 2026-04-03

  article
  PublisherDOI

• Additional file 1 of Metabolic targeting of pantothenate by medium chain fats in glioblastoma cells

  Figshare · 2026-04-07

  articleOpen access

  Supplementary Material 1.

  PublisherDOI

• GAA-based therapeutic strategies for neurological glycogen storage diseases

  Molecular Genetics and Metabolism · 2026-02-01

  articleOpen accessSenior author
  PublisherDOI

• Shaping Human Health and Nutrition Through Innovations in Spatial Metabolism

  Annual Review of Nutrition · 2026-05-19

  article

  Spatial metabolomics has emerged as a transformative approach for understanding how metabolism is organized within tissues and how nutritional factors influence health and disease. By preserving the spatial context of metabolites within intact tissue architecture, techniques such as MALDI and DESI imaging mass spectrometry reveal metabolic heterogeneity that bulk analyses cannot capture. This review examines how spatial metabolomics advances nutrition research across multiple domains: from mapping nutrient distributions in foods to understanding how diet reshapes tissue metabolism in disease states. We highlight recent innovations, including single-cell-resolution imaging, 3D metabolome reconstruction, stable isotope tracing, and multiomics integration. Key applications demonstrate how dietary patterns drive glycogen accumulation in cancer, alter lipid zonation in fatty liver disease, and modulate brain metabolism through the gut-brain axis. These spatially resolved insights establish direct mechanistic links between nutrition, tissue metabolism, and disease pathogenesis.

  PublisherDOI

• Mass Spectrometry-Based Spatial Imaging of the Cochlea

  Journal of the American Society for Mass Spectrometry · 2026-04-03

  articleOpen access

  Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) is transforming spatial molecular studies. However, applying MALDI-MSI to small, anatomically complex tissues remains challenging. One such structure is the cochlea, the auditory part of the inner ear that is critical for hearing. To address these challenges, we developed and implemented a streamlined workflow for sample preparation and processing to obtain MALDI-MSI data on mouse cochlea. Sample acquisition was optimized to minimize time and processing steps, allowing use of flash-frozen neonatal mouse heads. This workflow enabled high spatial resolution metabolomic and lipidomic imaging of the sagittally cryosectioned mouse cochlea using N-(1-naphthyl) ethylenediamine dihydrochloride (NEDC) matrix via sublimation. Optimized NEDC sublimation allowed high signal-to-noise, reduced delocalization, and salt tolerance, allowing acquisition of 5 μm-resolution imaging data on a MALDI-MSI instrument. Sublimation was found to be superior to spraying as a method for matrix application due to its higher signal-to-noise, particularly for lipids and fatty acids, and improved spatial resolution. Diverse metabolites and lipids were measured throughout the cochlear region, revealing distinct spatial distributions. Clustering identified reproducible physiological regions, including the otic capsule and spiral ducts. High spatial resolution imaging revealed distinct tissues, cell types, and molecular signatures within the cochlea. These findings establish the utility of high spatial resolution MALDI-MSI for auditory research, enabling molecular mapping of cochlear function and dysfunction.

  PublisherDOI

• Metabolic Coherence of the Mouse Brain

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-09

  articleOpen access

  The brain's metabolic demands are well established, but how metabolism is coordinated across anatomically distinct regions remains poorly understood. Here, using matrix-assisted laser desorption/ionization (MALDI) imaging integrated with the Allen Brain Atlas and optimal transport-based computational analysis, we map the spatial metabolome across twelve major mouse brain divisions. We define an optimal-transport-derived inter-regional metabolite similarity metric and refer to it as metabolic coherence. This structure is largely preserved in an amyloid mouse model of Alzheimer's disease despite widespread changes in individual metabolite and lipid levels. Individual metabolites and lipids shift in a coordinated manner across regions, sustaining inter-regional relationships even as absolute levels change in patterns indicative of mitochondrial dysfunction. To test whether the coherence metric is responsive to local intervention, we targeted the left hippocampus of mice from this model via lentiviral shHIF1α knockdown or neuronal AAV-mediated AOX expression. Both interventions were associated with metabolite normalization at the injection site. More importantly, normalization extended across distal regions sharing high metabolic similarity with the hippocampus and was accompanied by improved social memory in a single behavioral assay. Gene modulation and amyloid plaque reduction localized to the injection site.

  PublisherOA PDFDOI

• Metabolic targeting of pantothenate by medium chain fats in glioblastoma cells

  Figshare · 2026-04-07

  otherOpen access

  Abstract Ketogenic diets are commonly used for epilepsy therapy and are increasingly being considered in cancer treatment, where metabolic reprogramming triggered by glucose restriction and ketosis alters energy provision as the therapeutic mechanism. However, a recently developed medium chain triglyceride product, with a high decanoic acid (DA) to octanoic acid (OA) ratio (DA: OA) has enabled a much less restrictive diet and is clinically effective as an epilepsy treatment, yet no studies have explored the product in cancer models. Here we investigate metabolic mechanisms of DA, OA and DA: OA using a cellular glioblastoma model, focusing on changes in energy metabolism. We show, at a transcriptional level, that DA provides the dominant regulatory influence, enhancing transcription of fatty acid and amino acid metabolism pathways, while reducing cancer-associated glucose metabolism and kinase pathways. DA: OA treatment shared some of these effects, with little influence from OA. At a protein level, DA: OA treatment played the dominant role, regulating metabolic, cancer and signalling pathways, including a large network centred around albumin and protein kinase activities. Finally, at a metabolomic level, both DA and DA: OA treatment reduced vitamin B5 (pantothenate) levels, which is necessary for the synthesis of coenzyme A used in the activation of fatty acids for energy provision, suggesting a novel mechanism to reduce cellular energy provision in cancer. Importantly, these effects occur under high glucose conditions. Thus, we show that decanoic acid-rich treatments may regulate glioblastoma cell biology through targeted effects on glucose and fatty acid metabolism and kinase signalling and may trigger a potential reduction in pantothenate levels in glioblastoma cells, providing a potential novel therapeutic mechanism in cancer treatment.

  PublisherDOI

Recent grants

• Regulation, signaling, and dynamics of glucan phosphatases

  NIH · $3.6M · 2010–2020

• Brain Glycogen-Metabolism,Mechanisms, and Therapeutic Potential

  NIH · $8.2M · 2020–2028

• Treatment of Lafora disease with an antibody-enzyme fusion

  NIH · $383k · 2019–2022

• NIH Grant K99NS061803

  NIH · $154k · 2009

• Aberrant Glycogen in Lung Adenocarcinoma Tumorigenesis

  NIH · $2.1M · 2022–2027

Frequent coauthors

• Ramon C. Sun

  University of Florida

  155 shared

• Lyndsay E.A. Young

  University of Kentucky

  85 shared

• Pascual Sanz

  Centre for Biomedical Network Research on Rare Diseases

  64 shared

• Craig W. Vander Kooi

  University of Florida

  55 shared

• Lindsey R. Conroy

  University of Kentucky

  40 shared

• Tara R. Hawkinson

  University of Florida

  38 shared

• M. Kathryn Brewer

  Institute for Research in Biomedicine

  34 shared

• Carlos Romá-Mateo

  Centre for Biomedical Network Research on Rare Diseases

  30 shared

Labs

• Gentry LabPI

Education

• Ph.D., Biochemistry and Molecular Biology

  University of Florida

  2006

• M.S., Biochemistry and Molecular Biology

  University of Florida

  2002

• B.S., Biochemistry and Molecular Biology

  University of Florida

  2000

Awards & honors

• 2014 NIH IDeA Maciag Award
• 2017 NIH CCTS mentoring award
• 2018 NINDS Story Landis award
• 2020 Academy of Medical Educator Excellence in Medical Educa…