Jeff Jones, Ph.D., is an assistant professor of neuroscience at the University of Florida’s College of Medicine. His research explores age-related metabolic changes in neurons during normal cognitive aging and dementia and how these changes affect DNA, with the goal of discovering new treatments.
Q: What is the most exciting discovery you’ve made so far?
A. As a postdoc under my mentor Dr. Fred Gage at the Salk Institute for Biological Studies in San Diego, we harnessed a model directly converting aged human dermal fibroblasts, or skin cells, into aged neurons. These skin cells — from neonates to the elderly — maintain that age when you directly convert them. So you can ask: What is it that drives aging in a neuron in vitro? It allows one to model human aging in a dish, and that property makes it a unique model system. And then you can ask: What is it that separates someone with no family history of Alzheimer’s disease who goes on to develop dementia from someone who ages healthy throughout their whole life?
Q: What inspired you to focus on this area of neuroscience?
A. When I was in high school, my mom had breast cancer, and I was just learning to drive at the time. So I was using my learner’s permit to take her to chemotherapy. I remember thinking, what is cancer? I just know it’s a bad thing. So I kept asking the oncologists: What is cancer? And they kept giving basic explanations, but I wanted to know more. One oncologist recommended that I pursue this as a course of study in college. I took that advice as an undergraduate at the University of South Florida, and I pursued cellular and molecular biology.
My jump to neuroscience was by chance. I was reaching out to cancer labs and any lab I could think of, cold-calling professors for a research position. Fortunately for me, Dr. Chad Dickey had an opening. I started working on cell culture models and began understanding a little bit of neuroscience, mostly basic molecular and cellular biology in the context of Alzheimer’s disease. Within the first year, I was like, this is awesome — the environment was exciting and challenging and I decided to stick with it. I then had a chance to collaborate with organic chemists, led by Dr. Bill Baker, where we isolated bioactive molecules from a plant called bayberry. We were able to show in cell cultures and mouse tissue that this naturally produced substance reduced the overall burden of tau, a protein implicated in multiple neurodegenerative diseases.
For my Ph.D., I worked in the lab of Dr. Su-Chun Zhang at the University of Wisconsin-Madison, and my research project centered around a rare and deadly disorder called Alexander Disease that arises from de novo mutations in the gene for Glial Fibrillary Acidic Protein (GFAP). Working with Dr. Zhang and Dr. Albee Messing, we were able to recruit two Alexander disease patients, and at the time, the CRISPR revolution was just starting. We generated induced pluripotent stem cells (iPSCs) from the patients and used CRISPR to genetically correct the GFAP gene. We then generated astrocytes from both the mutant and genetically corrected lines to gain insights into the mechanisms resulting in Alexander disease. My thesis project showed that the intermediate filament GFAP is partly responsible for the movement of organelles within astrocytes in this disease, and if you lose it, you lose the ability to organize the cellular architecture, which has implications for the function of the entire brain.
Q: How do you envision your research advancing neurological disease treatments?
A. While one focus of the Alzheimer’s research field is familial mutations, our lab is taking a different route. Familial Alzheimer’s only represents about 5% of all dementia cases, and we know that people who have a certain mutation are at higher risk. Our lab is looking at the 95% of Alzheimer’s cases with no known genetic component. We’re studying age-related metabolic changes in neurons, to understand their role in neurodegeneration. We think changes in metabolism could be a therapeutic avenue. And this could extend far beyond Alzheimer’s and have implications for normal cognitive aging.
Q: What makes working in your lab different from other research environments?
A. All our science is done on human cells in culture. Our statistical power comes from the genetic diversity of patients, rather than from one cell line or genetically identical mice. We have genetically distinct samples that reflect people in our population. I think that makes us pretty unique, at least for a nonclinical lab focused on neural genetics and metabolism. Hopefully our work will find features that unite a lot of patients.
Q: What do you enjoy doing outside of work?
A. I am a big tinkerer. During the pandemic, I made a homemade air quality detector by soldering cheap sensors that measure CO2, humidity, temperature, and particulate matter and then writing up some code. I collected data on the air quality in my apartment and then plotted it over time with Python scripts. My wife and I also enjoy spending time with family. We just welcomed a new baby niece, Nova, and we’re very much looking forward to being the fun relatives who introduce her to ice cream earlier than her parents would prefer.