Matthew Gentry: Biofuels, Epilepsy and Science Advocacy

Podcast | Jul 27, 2017

In May, it was my distinct pleasure to present Matthew Gentry with a University Research Professorship award. He was one of 16 faculty, selected by their own colleges, who have demonstrated excellence in scholarship and creative work that addresses scientific, social, cultural and economic challenges in our region and around the world.

Gentry, a professor of molecular and cellular biochemistry in the College of Medicine, has received an NSF Faculty Career Development Award, NIH Pathway to Independence Award, three U.S. patents, and a five-year, $8.5 million NIH grant to pursue a cure for Lafora disease, a deadly congenital form of epilepsy.

His research began with a plant protein that controls the production of biofuels. It turns out mutations in a similar protein in humans result in Lafora disease. He explains, “The discoveries that we made in the plant system were directly applicable to the human system, and that led us down this road now of studying this human disease with the realistic and hopeful possibility of a therapy in the next two to five years.”

Gentry, who spends time advocating for science funding through the American Society for Biochemistry and Molecular Biology, says, “We advocate that money shouldn't be set aside for specific diseases because while you're researching disease X, you can find something that impacts disease Y. And if you set that money aside, then you don't let the best science get done.”

Listen to the podcast to hear why Gentry says the breadth and depth of the research environment at UK is uniquely strong.

Matthew Gentry: Biofuels, Epilepsy and Science Advocacy - Podcast Transcript

Have you ever wondered who was doing the research that will impact your future? The research podcast lets you met those people, and learn how the University of Kentucky is exploring and strengthening our understanding of the world through research and discovery.

Here's Alicia Gregory, director of Research Communications.

Alicia: Today we’ll meet Matthew Gentry, a professor in the UK College of Medicine and director of the Lafora Epilepsy Cure Initiative.

Matt Gentry: So, I'm from a small town of about 1200 people, and everyone in southern Illinois; they were either a farmer or worked in the factory. And so my dad worked in the factory, grandparents. And the push was; go to college to learn a white collar trade. And I tried - tested out with Pharmacy and Physical Therapy, and Medicine, and nothing clicked. Nothing felt right. And then I started taking upper level biology courses, and biochemistry, and upper level chemistry. And things started making sense, and it was just this- following what made sense and what felt right. And once I learned about this field of biochemistry and how cells work, and trying to understand that, it was an obvious choice. And it really didn't become a choice, it just became kind of who I became.

Alicia: So tell me a little bit about the area of research you're focusing on right now.

Matt Gentry: So in my lab here at UK, we work on both biofuels and epilepsy. Which are two things you would think are not very closely related. And the reason we study both is we're interested in proteins. And proteins are the workers inside of a cell. They are the machines that make things happen. And so, our really ground breaking discovery came when we found that this plant protein does a specific process. And once we understood how the plant protein worked, we could apply it to this human disease. And the connection really between the two is that both plants, as well as algae, and humans have to store sugars. And the way they store those are a little different form, but they use the same protein to do that. And, in plants, if you can harness those proteins that are storing the sugars, then you can control biofuels. And in humans, if you have mutations in those proteins, then you get this fatal epilepsy disease called Lafora's Disease. It's an ultra-rare disease. So only, say, 1 out of 1.5 to 2 million people suffer from it. So, you might ask, you know, why should the NIH, the National Institute of Health, fund a disease like that? And the answer is that, you know, it gives us insights into how the body works that we wouldn't otherwise understand.

And so this particular disease, the kids develop normally until around age 12 to 15. They have an epileptic episode, and then those episodes increase in both severity and number over the next decade. And then by age 25 to 30, 100% of the patients die. And so it's an incredibly devastating disease because the parents lose a child, but the diagnosis typically doesn't happen until around age 18. So, by then they probably have more kids. And there's a 25% chance that each of their kids could have the disease. So, I've met families that have four children with this disease, and the parents, they know exactly what the fate is going to be for each of them, because they've seen what happened to their first.

We put together, about a year and a half ago, a collaborative team with myself here at UK, a group at Indiana University, a group at UT Southwestern, a group in Barcelona, and one in Madrid, focused on pooling our collective knowledge and effort to cure the disease.

So the plant work is funded by the National Science Foundation, and that was integral to getting our understanding of the disease. And now the disease work is funded by the National Institutes of Health. And so the discoveries that we made in the plant system were directly applicable to the human system, and that led us down this road now of studying this human disease with the realistic and hopeful possibility of a cure in the next 2 to 5 years.

Alicia: I think your story is really interesting in terms of the fact that you have plants and human. I think there might be more of those connections out there that, unless we research a lot of different things, we're going to miss.

Matt Gentry: Exactly. And so that's why, you know, I do quite a bit of science advocacy and the group that I'm a part of, the American Society for Biochemistry Molecular Biology, we advocate that money shouldn't be set aside for specific diseases because, while you're researching disease X, you can find something that impacts disease Y. And if you set that money aside, then you don't let the best science get done, and you don't know where you're going to have that impact at.

Alicia: And I think that's one of the things that people don't understand about science. Is you don't always find what you think you're going to find. You find something else entirely.

Matt Gentry: Right. I mean, I started working on plant proteins, and I'm now working on a human disease. So, you just have to go where the science takes you, and be willing to go on that journey.

Alicia: So tell me a little bit about the most fulfilling moments for you, in regards to your research.

Matt Gentry: So, the most fulfilling moments that I have had personally, is when you make that connection that others have missed, that usually starts in the literature. You've got to be a good student, and you know, most things are online now, but there are papers from the 1930s and ’40s that you still have to go to the library and look at. And so, when you make that initial discovery on paper, and you form that hypothesis, and then you take that to the bench and test it. I remember doing that when I was a postdoc at UC San Diego, and we got this result during the day. And I just had to drive back to the lab that night to make sure that I got the same result. And it's an incredibly rewarding experience to see that thought process become an actual discovery.

Alicia: How has your research impacted the way you train students?

Matt Gentry: So, you know, when I first started in research, I didn't know how to do most anything. I was terrible at the bench. And I'm surprised my boss didn't kick me out of the lab. But he let me fail to a point where I didn't get frustrated, but I was able to learn how to be a scientist. And I think that's really important in training people. You've got to teach them how to be independent. I don't want my students with me all the time. Right? I want to see them move on and succeed. And so, letting them, and teaching them how to do science at the bench, how to write about what they found, and how to speak about it, then lets them become independent. And that's a really fun process.

Alicia: So what is the most challenging part of the work that you're doing?

Matt Gentry: The most difficult challenge that we face is funding. And so from 1997 to 2007, the U.S. did a doubling of the National Institutes of Health budget. And so, about 35 to 40% of all scientific ideas were being funded and being turned into fundable projects that people could work on. But then from 2007 until now, we've seen stagnation, and we've lost about 20% of our purchasing power. And that means that only about 12 to 15% of ideas get funded. So scientists now spend really an inordinate amount of time writing grants instead of doing the work. And so that's frustrating to see that happen. So, you know, I and others do a lot in the advocacy space, not directly associated with UK, but just a private citizen, where we contact our congressman and senators and let them know that this biomedical work - it's important for our nation in terms of budget, in terms of being competitive overseas, and in terms of our health care.

Alicia: So how long have you been here at UK?

Matt Gentry: So I've been at UK for almost 9 years now. I came here from UC San Diego, and directly into the College of Medicine.

Alicia: So what inspired you to come here?

Matt Gentry: I think what inspired me to come to UK is exactly the reason I'm still here. And that's because we had really strong leadership at the time when I came, when I got here, we had a very strong department chair and the College of Medicine was doing very well under the dean at that time. And I'd say that's exactly what we've got now. So, from President Capilouto, Vice President of Research Lisa Cassis, and the Dean of the College of Medicine Robert DiPaola, we've got leadership that takes care of the administrative issues so that scientists can do science. We're often times not good at pushing papers, and some of us are bad at math, but we're good at science. And so, letting scientists do science is what I think we all want, and we've got the leadership that allows us to do that now.

Alicia: If you were talking to someone who was considering joining UK as part of the research enterprise, what would you tell them about the environment here?

Matt Gentry: So the environment here at UK is uniquely strong because of its breadth and depth. And so, you know, you look at the different colleges, we've got the College of Ag, we've got the College of Engineering, we've got the College of Medicine, and then the Arts and Sciences campus. And so to have that breadth of knowledge here is incredibly exciting. Especially for my lab, where we are bouncing between agriculture and human disease, and you couple that with the infrastructure that the current leadership has invested in, and then knowing that we have strong leadership at the President, Vice President of Research level, and the Dean in the College of Medicine; it's an exciting time to be here. And it's exciting just to be able to focus on science and do science, and not have other distractions.

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