All comments here are made in my individual capacity and not on behalf of St. Jude and are not reviewed or approved by St. Jude.
Our team had a zoom interview with Dr. Jason Vevea, Ph.D., the Department of Developmental Neurobiology, St. Jude Children’s Research Hospital to learn about his work in Alzheimer subject. The transcript of our interview is below.
Hana Barber 0:00
So, I guess we can just quickly, briefly introduce ourselves. Hi, my name is Hana Barber. I’m the co-founder and president of the Musical Memories Project, and today we are joined by Dr. Jason Vevea from St. Jude Research Hospital, who conducts research in the Developmental Neurobiology Department at St. Jude.
Stephen Brezinski 0:23
Yeah. This past summer, I worked in the Developmental Neurobiology Lab with Justina and Dr. Little as well. That’s how we originally got connected—I was in the High School Research Immersion Program that summer.
Dr. Vevea
Did you see me around?
Stephen Brezinski
I don’t remember your face.
Dr. Vevea 0:52
That’s pretty characteristic of those programs, yeah.
Stephen Brezinski 0:53
Yeah. But, yeah, I play percussion in the group, and, yeah, that’s me.
Rehan Krishnan 1:03
I’ll go ahead. I’m Rehan Krishnan, and I’m a member who just comes to play piano. I have a very big interest in neuroscience, so I got really interested in your research. I love synaptic plasticity. It’s currently my main focus of interest, and I’d say dendritic topology is what I like most. I really think what you’re doing with the postsynaptic and presynaptic cycle is fascinating.
Amal Ahmed 1:36
I’m Amal Ahmed. I don’t have much cool stuff to say, but I’m really just here to learn and hear about what you’re doing at St. Jude.
Dr. Vevea 1:44
That’s the coolest thing of all—being here to learn.
Hana Barber 1:50
Okay, so I guess we’ll just jump in with the questions. Could you tell us who you are and more about your specific area of research?
Dr. Vevea 2:00
So, my name is Jason Vevea, and I started my lab here at St. Jude just a couple of years ago. We could talk about a lot of different things—my research career path, for instance. That actually might be an interesting place to start.
After high school, I didn’t know what I wanted to do. I went to a junior college for a while and got really excited about some of the hard classes I was taking—organic chemistry, physics, calculus, and so on. I really started to love science, so I went to a state university and majored in biochemistry and microbiology. Biochemistry is a fantastic major if you’re undecided; it gives you a really good foundation for anything in biology or lab sciences.
From there, I got interested in lab work. I got a tech job in a lab, gained some experience, and saw the environment firsthand. These people came in every day, planned out their experiments, assembled them, ran them, analyzed the data, read papers, debated about the most recent science coming out, and discussed how it affected their research and the broader field. It was thrilling. I was convinced to go to graduate school.
I was lucky enough to get into a great school in New York, where I did my Ph.D. work in yeast cell biology—specifically in Saccharomyces cerevisiae (Baker’s yeast). It’s a great model organism. We use many model organisms in cell biology—rodents, yeast, C. elegans (the worm), Drosophila (the fly). They’re key to advancing science. Even though yeast is a single-cell organism, it has mitochondria, a nucleus, endoplasmic reticulum, vacuoles—all that stuff.
I fell in love with cell biology, but toward the end of my Ph.D., I realized I wanted to branch out for my postdoc work. After your graduate work, you do a postdoc, kind of like how medical school is followed by a residency before you can practice independently. Residency and postdoc training are equivalent in that sense.
For my postdoc, I searched for a neuroscience lab because I found neuroscience fascinating. It’s the study of the brain—the universe understanding itself. Neurons are incredibly beautiful, highly polarized structures. They have distinct compartments: soma, dendrites, and axons that can be millimeters or even meters long in humans.
I continued to fall in love with the biology of neurons, and during my postdoc, I specifically focused on presynaptic biology, which is where all the cool stuff happens—the synaptic vesicle cycle. Synaptic vesicles are small, neurotransmitter-filled organelles that fuse with the active zone, release neurotransmitters to signal the next cell, and then get taken back up and reformed within seconds. It’s an amazing membrane and protein trafficking event that happens hundreds of times per second at each synapse. Given that we have billions or even trillions of synapses in the brain, it’s astounding that this process continues flawlessly throughout our entire lives.
That’s what made me want to keep studying it. But I also started thinking about how to impact human disease. There are two reasons to study biological sciences: one is curiosity—we want to learn how the machine works. The other is application—if we understand how it works, we can fix it when something goes wrong.
Neurodegenerative diseases like Alzheimer’s and Parkinson’s are one-way streets—no one has survived an Alzheimer’s diagnosis. These diseases seem to begin with presynaptic dysfunction. That’s why I started my lab—to study this fascinating structure while also addressing one of the biggest unmet medical challenges.
We can talk about the tools I use, the specific proteins I’m interested in, early findings from my lab—whatever you all want.
Stephen Brezinski 7:50
Okay, well, I have a question. Could you explain how Alzheimer’s specifically affects different areas of the brain, particularly those related to memory, emotions, and cognition?
Dr. Vevea 8:01
Yeah, that’s kind of difficult. We don’t really know, right? Alzheimer’s and Parkinson’s seem to start in different areas of the brain—like the substantia nigra or locus coeruleus, and the hippocampus. Why that happens is still a big question. There are a lot of hypotheses, but we don’t fully understand why those neurons are particularly sensitive.
I think the key to understanding these diseases is figuring out why those neurons are more vulnerable to specific stresses. Right now, most of what we know about Alzheimer’s and similar neurodegenerative diseases comes from histopathology. We can identify things like amyloid plaques and tau tangles, but beyond that, there’s still a lot of uncertainty.
Over the past 30 years, a major focus has been on targeting these protein aggregates—like beta-amyloid and tau—as potential treatments. The idea was that if we could get rid of them, we could slow or stop the disease. But clinical trials haven’t been very successful. Many treatments have either shown no effect or, in some cases, actually made things worse. Some patients developed severe inflammation, brain bleeds, or other side effects.
Even when amyloid plaques were successfully reduced, it didn’t necessarily improve cognitive function. So now, there’s a shift in thinking—maybe we don’t fully understand the underlying mechanisms of the disease yet. That’s where my research comes in.
Rehan Krishnan 11:29
So, are you suggesting that by the time amyloid plaques first form, it’s already too late to start treatment?
Dr. Vevea 11:39
Again, tough question. The answer is—we don’t really know. We can image amyloid in older individuals, and there are cognitively normal people who have significant amyloid buildup. On the other hand, some people with very little amyloid burden have severe memory deficits.
It’s not as straightforward as “amyloid equals Alzheimer’s.” While amyloid may play a role, there could be other underlying processes that are driving the disease. That’s why I focus on understanding synaptic dysfunction—because it may be an earlier and more fundamental part of the disease process.
Rehan Krishnan 12:39
Are there any recent discoveries at St. Jude related to neurodegenerative disease research that you’re particularly excited about?
Dr. Vevea 12:48
That’s a great question. St. Jude is primarily a children’s research hospital, so our main focus isn’t on aging-related diseases like Alzheimer’s. But we’re starting to see connections between pediatric treatments and long-term cognitive effects.
For example, St. Jude has been extremely successful in treating childhood cancers, especially brain tumors. But now, we’re seeing that some of these survivors—who received treatments like radiation therapy—are experiencing cognitive decline as they age.
These patients are completely cured of their cancer, but decades later, they start showing signs of cognitive impairment that resemble Alzheimer’s. Some of the same risk factors for Alzheimer’s, like the ApoE4 gene, also seem to make certain patients more vulnerable to long-term effects of radiation.
Interestingly, there are also sex-specific differences. Women have about twice the risk of developing Alzheimer’s compared to men, and they also seem to be more affected by radiation-induced cognitive decline. This is something we’re actively studying to understand why.
Amal Ahmed 17:57
How does St. Jude specifically facilitate collaboration between researchers working on neurodegenerative diseases and those in other fields like genetics or oncology?
Dr. Vevea 18:10
That’s actually one of the best things about St. Jude—the level of collaboration here is incredible. At many universities, researchers compete for funding, space, and recognition, which can create barriers to collaboration. But at St. Jude, we’re all encouraged to work together.
For example, different labs have access to specialized equipment, and rather than hoarding resources, we share them. If one lab has expertise in a particular technique—say, a specialized imaging method—another lab can collaborate with them instead of trying to develop it from scratch. That culture of openness really accelerates research progress.
Stephen Brezinski 19:36
What advancements are being made in identifying biomarkers for early detection of Alzheimer’s and other neurodegenerative diseases?
Dr. Vevea 19:45
That’s an extremely tough challenge. There are a few promising directions—some researchers are looking at phosphorylated tau levels in cerebrospinal fluid (CSF) or using PET scans to detect amyloid. There have also been studies on lipid biomarkers in the blood.
But diagnosing Alzheimer’s is still difficult because there’s no single test that can definitively confirm it in a living patient. Right now, the best thing people can do is focus on general brain health—exercise, a healthy diet, and staying cognitively engaged.
Rehan Krishnan 21:01
I wanted to circle back to the discussion about proteins like apolipoproteins and biomarkers. Could you tell us more about the specific proteins you’re studying in the presynaptic process?
Dr. Vevea 21:17
Absolutely. One of the big projects in my lab involves developing a new technique to rapidly isolate synaptic vesicles. Traditionally, this process took days, but we’ve refined it down to about 30 minutes while maintaining a high level of purity.
With this method, we can analyze how synaptic vesicle composition changes across the lifespan. We’ve identified proteins related to the complement cascade and lipid signaling that increase dramatically with age. These might be key players in synaptic dysfunction and early markers of neurodegeneration.
The next step is figuring out whether these proteins are simply byproducts of aging or if they actively contribute to synaptic failure. We’re now doing mechanistic studies to see how they interact with known synaptic proteins and whether modifying their levels can rescue function.
Stephen Brezinski 24:19
Since you’re in the Developmental Neurobiology Lab, do you use techniques like gel electrophoresis, organoids, or qPCR in your research?
Dr. Vevea 24:38
Yes, we use many of those techniques, but aging-related diseases are hard to model in vitro. We rely heavily on aged rodents because they provide the best physiological context for neurodegeneration.
However, we also use simpler models, like dissociated neurons cultured in a dish. This allows us to manipulate individual genes or proteins and visualize their effects under a microscope. We’re even working on reconstituting synaptic processes using purified proteins in test tubes to isolate specific molecular interactions.
Hana Barber 26:34
Well, thank you so much for your time today. We’ve learned so much from you, and we’re definitely very interested in continuing to explore this field. Thank you for your work and for speaking with us.
Dr. Vevea 26:49
Absolutely! You all are really sharp—this has been a great conversation. I’m feeling energized to get back to the lab. If any of you are interested in doing research at St. Jude, definitely reach out.
Stephen Brezinski 27:10
Yeah, I got involved through the High School Research Immersion Program.
Dr. Vevea 27:12
Exactly. Programs like that are a great way to get experience, but you can also directly email a principal investigator (PI) to ask about opportunities. Many labs welcome summer students, and sometimes reaching out personally is the best way to get involved.
All
Thank you!