Matthew S Gentry,
Professor & Chair
About Matthew S Gentry
Dr. Matthew S. Gentry is Professor & Chair of Biochemistry & Molecular Biology in the College of Medicine at University of Florida. He is a prominent brain metabolism scientist who has made seminal discoveries in the realm of brain glycogen and glucose metabolism and how perturbations in these pathways impact neuro-centric diseases. Dr. Gentry has nearly 20 years of experience working on glycogen storage diseases (GSD). He did research on cell signaling and cell division at Syracuse University for his Ph.D in Molecular Biology (2003) and then worked on the GSD and childhood dementia called Lafora disease as a postdoctoral scholar in the laboratory of Dr. Jack Dixon at UC-San Diego where he defined the biochemical properties of the genes mutated in the disease. Building on this foundational biochemistry, he has been continuously funded by NIH since 2007 via a K99/R00; multiple R01 grants; a P01; a recent R35 that focuses on Brain Glycogen – Metabolism, Mechanisms, and Therapeutic Potential; other NIH grants; and funding from foundations and industry. He has also been continuously funded by NSF since receiving a NSF CAREER award in 2013 to study the enzymology and structure/function of metabolic enzymes. His lab works on a number of CNS-centric GSDs, Alzheimer’s disease, and the role of glycogen in both lung cancer and Ewing sarcoma. The lab focuses on defining disease mechanisms, developing pre-clinical drugs and establishing clinical biomarkers. He has published >100 scientific papers and holds multiple patents.
Accomplishments
Teaching Profile
Research Profile
Dr. Gentry is Director of the NIH-established Lafora Epilepsy Cure Initiative (LECI) and Chair of Biochemistry & Molecular Biology at University of Florida. The LECI is a consortium of Lafora disease (LD) researchers from around the world that was established by a NIH P01 (PI: Gentry) to define the basic mechanisms of LD and translate the findings into pre-clinical therapies. LD is a glycogen storage disease, progressive myoclonic epilepsy, and childhood dementia. He has been working on LD for 20 years to define the disease-causing mechanisms of this fatal autosomal recessive disease and to develop therapies. This work has yielded three therapeutic platforms: traditional small molecule, anti-sense oligonucleotide, and an antibody-enzyme fusion. Each drug targets glycogen and either down-regulates glycogen metabolism or degrades aberrant glycogen-like aggregates. He is also PI of a non-overlapping NINDS R35 on brain metabolism and has been continuously funded by NIH since 2007. In collaboration with Ramon Sun (Associate Professor, UF BMB), they established a pipeline to perform traditional and spatial metabolomics on samples from control and diseased mice that yielded foundational insights into both normal and diseased metabolic pathways. Collaborating with the Sun laboratory at UF, the Gentry laboratory studies: Alzheimer’s disease, Lafora disease, Glut1 Deficiency Syndrome, Pompe disease, Cori disease, traumatic brain injury, spinal cord injury, lung cancer, and Ewing sarcoma while collaborating with numerous other labs on exciting projects.
LD is caused by mutations in either the gene encoding for laforin or the gene encoding for malin that when mutated results in pathogenic polyglucosan bodies (PGBs). Gentry discovered the activity of malin as an E3 ubiquitin ligase and laforin as a glycogen phosphatase, characterized their biochemical properties, determined the first crystal structures, developed assays to characterize their substrate specificity, defined their functions in vivo, established novel methodologies to assess PGBs, and developed an antibody-enzyme fusion (AEF) to degrade PGBs. Excitingly, the AEF ablates PGBs in vivo in LD mouse models in muscle, heart, and the brain.
His lab has also collaborated with biotech companies to develop both a small molecule and anti-sense oligonucleotide (ASO) to inhibit PGB formation. Excitingly, each of these therapeutics has progressed through large mammal testing and are advancing towards the clinic with the small molecule successfully completing a Phase I clinical trial (NCT05249621). While the ASO and small molecule stop disease progression in multiple mouse models, the antibody-enzyme fusion degrades pre-existing aggregates and normalizes brain metabolism. Thus, this therapy has the potential to reverse some disease progression.
His laboratory’s work has been recognized by the scientific community via invitations for review articles, talks at national/international symposia, and requests to serve on grant review committees. Dr. Gentry has been recognized for outstanding mentoring with the 2014 NIH IDeA Maciag Award, the 2017 NIH CCTS mentoring award, the 2018 NINDS Story Landis award, and the 2020 Academy of Medical Educator Excellence in Medical Education Award for Mentorship.
- Adult Polyglucosan Body Disease
- Alzheimer’s Disease
- Biomarkers
- Brain metabolism
- Cancer metabolism
- Carbohydrate metabolism
- Drug discovery
- Ewing’s sarcoma
- Glut1 Deficiency Syndrome
- Glycogen Storage Diseases
- Glycosylation
- Lafora disease
- MALDI Imaging
- Mass Spectrometry
- Neurodegenerative diseases
- Pompe Disease
- Toxoplasma gondii
- lung adenocarcinoma
Publications
Grants
Education
Contact Details
- Business:
- (352) 294-8387
- Business:
- matthew.gentry@ufl.edu
- Business Mailing:
-
PO BOX 100245
Biochemistry & Molecular Biology
Gainesville FL 32610 - Business Street:
-
ARB R3-234
1200 Newell Drive
GAINESVILLE FL 32610