Jeffrey R. Jones, PhD

Pioneering Research in Cellular Aging, DNA Damage, and Neural Development at the University of Florida

Explore Our Research

Featured Research Highlight

Dr. Jeffrey R. Jones

MBI Feature

The Jones Lab is featured on the McKnight Brain Institute website.

Flip to read more about our research and lab
McKnight Brain Institute • University of Florida

MBI Researcher Highlight

Dr. Jeff Jones in the lab

Research Focus

Exploring age-related metabolic changes in neurons during normal cognitive aging and dementia, with a focus on identifying therapeutic entry points through metabolic pathways.

Modeling Human Aging

Developing human-cell-based systems to study what separates healthy aging from dementia, enabling discovery work in a controlled, scalable in vitro setting.

The Human Cell Advantage

All research uses genetically diverse patient-derived cells rather than mice or uniform cell lines, making findings more representative of the real human population.

The 95%

While most Alzheimer's research targets rare familial mutations, the Jones Lab focuses on the 95% of cases with no known genetic cause, where metabolic changes may be key.

Read the full interview at McKnight Brain Institute →

Explore

Our Research

Cellular aging, DNA damage, neural development.

Flip to read more about our research

What we do

We combine human stem cell models, genomics, and functional assays to understand how aging impacts neural systems and identify interventions that preserve cognition and resilience.

Flip back

Technologies

CRISPR, iPSC systems, sequencing, bioinformatics.

Flip to read more about our research

How we do it

We leverage CRISPR engineering, iPSC-derived neural models, multi-omics (RNA/ATAC), and computational analysis (Python/R) to map mechanisms and test causality.

Flip back

Join the Lab

We're hiring — students, postdocs, and staff.

Flip to read more about our research

Open roles

If you're excited about neuroscience, aging, and human cell models, send a CV + brief note describing your interests and experience.

Flip back

Research Focus

🧬

DNA Damage & Aging

Understanding the cellular mechanisms of aging and their contributions to cognitive decline through advanced genomic techniques and bioinformatics analysis.

🔬

Stem Cell Biology

Expert in genetic engineering (CRISPR/Cas9), stem cell culture, human dermal fibroblast derivation, and transdifferentiation techniques.

🧠

Neural Development

Modeling brain disorders using induced pluripotent stem cells, organoids, and human neural development systems for disease research.

⚡

Cellular Metabolism

Investigating metabolic changes in aging cells and their role in neurodegeneration, with focus on glucose metabolism and energy production.

🔍

Next-Gen Sequencing

Developing and optimizing cutting-edge sequencing techniques with advanced bioinformatics skills in bash, python, and R for large data analysis.

🎯

Disease Modeling

Creating innovative disease models to study neurodegenerative conditions including Alzheimer's disease and Alexander disease using human cell systems.

Glucose Metabolism
DNA Repair
GFAP Mutations
Serotonin Neurons
Neural Aging

Restoring Hippocampal Glucose Metabolism

Our groundbreaking research published in Science demonstrates how restoring glucose metabolism in the hippocampus can rescue cognitive function across multiple Alzheimer's disease pathologies.

We discovered that glucose hypometabolism is a key driver of cognitive decline and that targeted metabolic interventions can restore memory formation and synaptic plasticity.

Key Findings:

  • Glucose metabolism deficits precede cognitive symptoms
  • Metabolic restoration improves memory consolidation
  • Synaptic plasticity is enhanced through glucose pathway modulation
  • Therapeutic potential for multiple AD pathologies
Glucose Metabolism Data
(Science 2024)
Glucose Metabolism Data (Science 2024)

DNA Repair in Postmitotic Neurons

Using innovative nucleoside analog incorporation mapping, we've identified genome repair sites in human neurons, revealing how DNA damage accumulates in the aging brain.

This work, published in Science, provides the first comprehensive map of DNA repair activity in living human neurons and demonstrates the vulnerability of specific genomic regions.

Key Discoveries:

  • First genome-wide map of neuronal DNA repair
  • Age-related decline in repair efficiency
  • Hotspots of DNA damage in critical genes
  • Novel therapeutic targets identified
DNA Repair Mapping
(Science 2021)
DNA Repair Mapping (Science 2021)

GFAP Mutations in Human Astrocytes

Our Cell Reports study reveals how mutations in GFAP (Glial Fibrillary Acidic Protein) disrupt organelle distribution and function in human astrocytes, leading to Alexander disease pathology.

Using patient-derived cells and CRISPR engineering, we demonstrated the molecular mechanisms underlying astrocyte dysfunction in neurodegenerative disease.

Major Findings:

  • GFAP mutations disrupt mitochondrial dynamics
  • Organelle trafficking is severely impaired
  • Cellular energy production is compromised
  • Novel therapeutic strategies identified
GFAP Organelle Analysis
(Cell Reports 2018)
GFAP Organelle Analysis (Cell Reports 2018)

Serotonin Neuron Generation

Published in Nature Biotechnology, this work established protocols for generating functional serotonin neurons from human pluripotent stem cells, opening new avenues for studying mood disorders and depression.

These neurons exhibit authentic serotonergic properties and provide an invaluable model for drug screening and disease mechanism studies.

Achievements:

  • First reliable protocol for human serotonin neurons
  • Functional neurotransmitter release demonstrated
  • Disease modeling applications validated
  • Drug screening platform established
Serotonin Neuron Data
(Nature Biotechnology 2016)
Serotonin Neuron Data (Nature Biotechnology 2016)

Neural Cell State Shifts in Aging

Our comprehensive review in Nature Reviews Neurology examines how neural cell states change during aging and in age-related diseases, providing a framework for understanding neurodegeneration.

This work synthesizes current knowledge on cellular aging mechanisms and identifies key pathways for therapeutic intervention.

Key Concepts:

  • Cell fate plasticity in aging neurons
  • Epigenetic changes drive dysfunction
  • Cellular reprogramming potential
  • Therapeutic intervention strategies
Aging Cell States
(Nature Rev. Neurology 2023)
Aging Cell States (Nature Reviews Neurology 2023)

Key Publications

Restoring hippocampal glucose metabolism rescues cognition across Alzheimer's disease pathologies
Minhas PS*, Jones JR*, Latif-Hernandez A*, et al. (* co-first authors)
Science, 2024
Incorporation of nucleoside analog maps genome repair sites in postmitotic human neurons
Reid DA, Reed PJ, Schlachetzki JCM, Nitulescu II, Chou G, Tsui EC, Jones JR, et al.
Science, 2021
Neural cell state shifts and fate loss in aging and age-related diseases
Traxler L, Lucciola R, Herdy J, Jones JR, Mertens J, Gage FH
Nature Reviews Neurology, 2023
Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes
Jones JR, Kong LH, Hanna IV, Michael G, Hoffman B, et al.
Cell Reports, 2018
Generation of serotonin neurons from human pluripotent stem cells
Lu J, Zhong X, Liu H, Huang CT, Sherafat MA, Jones J, et al.
Nature Biotechnology, 2016

About Dr. Jones

Dr. Jeffrey R. Jones is an Assistant Professor of Neuroscience at the University of Florida College of Medicine. His lab studies age-related metabolic changes in neurons during normal cognitive aging and dementia, and how those changes affect DNA, with the goal of uncovering new therapeutic avenues.

Dr. Jones completed his PhD at the University of Wisconsin-Madison in the laboratory of Dr. Su-Chun Zhang, where he used iPSCs and CRISPR to model Alexander disease in human astrocytes, revealing how mutations in the GFAP gene disrupt organelle architecture and cellular function. He then trained as a postdoctoral researcher under Dr. Fred Gage at the Salk Institute for Biological Studies, where he helped pioneer a model that directly converts aged human skin cells into neurons, preserving the donor's age in the process. This system makes it possible to study what separates healthy aging from dementia in living human neurons.

The Jones Lab takes a distinct approach: all research is conducted on human cells in culture, drawing statistical power from the genetic diversity of real patients rather than a single cell line or genetically identical mice. The lab focuses on the roughly 95% of Alzheimer's cases with no known genetic cause, investigating whether metabolic changes in aging neurons could serve as both a driver of neurodegeneration and a therapeutic target, with implications that extend well beyond Alzheimer's to cognitive aging more broadly.

Dr. Jeffrey R. Jones Dr. Jeffrey R. Jones

Research Expertise

CRISPR/Cas9 Gene Editing

Advanced genetic engineering techniques

Stem Cell Culture

iPSC derivation and differentiation

Organoid Technology

3D tissue modeling systems

Next-Gen Sequencing

RNA-seq, ATAC-seq, ChIP-seq

Bioinformatics

Python, R, Bash scripting

Disease Modeling

Neurodegeneration research models

Join Our Lab!

🏛️

Prospective Graduate Students Apply here

📧

Postdocs

Contact Jeff with a CV and cover letter.

🔬

UF Undergraduates

Fill out this form