Sound Effect: 0:14

[music]

Emily Davenport: 0:15

Welcome to"Cultivating Curiosity," where we get down and dirty with the experts on all the ways science and agriculture touch our lives, from what we eat to how we live. I'm Emily Davenport.

Jordan Powers: 0:27

And I'm Jordan Powers. And we're from the University of Georgia's College of Agricultural and Environmental Sciences.

Sound Effect: 0:34

[chime]

Jordan Powers: 0:35

So we are here today with Dr. Franklin West, Professor in the CAES, Department of Animal and Dairy Science and executive committee member of the UGA Regenerative Bioscience Center. Dr. West, thank you for joining us today.

Franklin West: 0:48

Thank you for inviting me. I'm excited to be here and talk about what we're doing.

Jordan Powers: 0:52

Absolutely. Well, as we get started, can you tell us a little bit about your background? And what drew you into Animal and Dairy Science?

Franklin West: 0:58

Yes, well, I've always been really excited about biology. So, my dad was in the military, and we lived in Italy. And I remember, as a four-year-old, my father helped me put together a net and we would go outside to the field next to our house. And we would collect crickets and hornets and all kinds of things. And we'd put them in a jar and observe them for a couple of days and take notes on their behaviors. And then we'd let them go the day after. So that kind of started my love with biology in general. And since then, I was really excited about science. And so in college, I actually did a lot of research with a gentleman named Dr. Lawrence Blumer, and Morehouse in Atlanta. And we studied things like mate choice and bean beatles. And then ultimately, it led to an internship at Princeton University with Jeanne Altman. And we were studying yellow baboons. And I got to go on a trip to Kenya. And so it was really exciting. We were studying yellow baboons, and their mate choice and how drought affected their hierarchy. And so I just really have been excited about science since the beginning, so to speak, so.

Jordan Powers: 2:05

And what specifically drew you into Animal and Dairy Science?

Franklin West: 2:08

So because of those earlier experiences, I was excited about ecology.

Sound Effect: 2:11

[chime]

Emily Davenport: 2:13

Ecology is the study of understanding how organisms interact with each other and their environment. Biotechnology harnesses biological processes to help in the development of new technology.[chime]

Franklin West: 2:24

And I wanted to combine that with biotechnology. And so there's another faculty member in the department who is my mentor, Steve Stice, he was interested in cloning. And so I was excited about combining endangered species conservation with cloning. And so just to kind of put that in perspective, every year a Florida panther is hit by a car, and so that narrows the gene pool, and Florida panthers are at a point where every time they lose a panther, the gene pool gets smaller and smaller. So essentially, they're breeding cousins to cousins. And so they have all kinds of health issues. And so the thought was, well, maybe you could collect a biopsy of a piece of tissue from these Florida panthers that had just died, clone those individuals and reintroduce their genetics back into the population. And so I joined the department as a graduate student in his laboratory. And he was doing some really exciting stuff, in addition to cloning with stem cells. And so then we started playing with stem cells, for a variety of reasons. But one project was, we're turning stem cells, human stem cells into sperm. And the idea was, we're going to be able to use that for infertile couples. But the way that ties back into endangered species is, we can now take a skin cell from that Florida panther that got hit by the car and turn that into a stem cell and turn that into sperm, and use that as an assisted reproductive technology. So, we've been hanging out together, me and Steve, for years. And these are the kinds of crazy things that go on in our labs. So.

Jordan Powers: 3:56

Science is amazing.

Everyone: 3:58

[laughter]

Jordan Powers: 4:00

I mean, if you could see our faces right now like, minds blown.

Everyone: 4:02

[laughter]

Emily Davenport: 4:04

Jaws on the table.

Everyone: 4:08

[laughter]

Emily Davenport: 4:08

So you mentioned stem cells. Can you share more with our audience about what that means?

Franklin West: 4:13

All right, so our lab is a stem cell laboratory. And I know at one point stem cells were highly controversial. So they were being derived from embryonic sources. However, today, we actually get it from skin cells. So Shinya Yamanaka in 2006, developed some groundbreaking technology where I could actually take a skin cell from any patient and add four to six genes. And that actually takes that skin cell all the way back to what we call a pluripotent state. And those cells are capable of forming any cell type in the body. So cardiovascular cells, neural cells, etc. And so we've gotten around the whole issue associated with that controversy by using this technology. He actually won the Nobel Prize for it, it's kind of how big it was, right?

Sound Effect: 4:59

[chime]

Jordan Powers: 5:00

We'll put a link to the Nobel Peace Prize-winning research in the shownotes for you.

Sound Effect: 5:03

[chime]

Franklin West: 5:04

So these stem cells are capable of turning any cell type in the body and what we do is we take skin cells, turn them into neural stem cells, then transplant them into the brain tissue and the neural stem cells turn into astrocytes and oligodendrocytes in neurons.

Jordan Powers: 5:18

So you're doing all this work with stem cells and endangered species. What does this mean for regenerative bioscience?

Franklin West: 5:24

Yes. So our lab, we're still excited about endangered species conservation. But we have gotten into what's more traditional, which I don't think regenerative bioscience is traditional in any sense of the word. But regenerative bioscience is basically we're taking different scientific approaches to enhance tissue regeneration in the body. And so there's a number of groups that are working together to address a variety of different conditions. So, for example, Jin Xie, in the chemistry department, who we work with, he's using nanoparticles to deliver signaling factors that promote tissue regeneration. And then we also work with other laboratories that are using hydrogels and different extracellular matrices to improve tissue regeneration in the brain after traumatic brain injury. So basically, regenerative bioscience is taking a number of different science technologies, combining them together to promote endogenous or natural recovery in the body from Parkinson's, Alzheimer's, to other types of injuries as well.

Emily Davenport: 6:27

So magic.

Franklin West: 6:28

Basically. It's basically magic.

Everyone: 6:30

[laughter]

Jordan Powers: 6:32

Truly life changing for countless people though, which is incredible.

Franklin West: 6:36

It is, it is.

Jordan Powers: 6:38

Tell us a little bit about your role with the Regenerative Bioscience Center.

Franklin West: 6:41

Yeah, so as an executive committee member, what we do is we try to develop different programs to help foster collaborations between different members as part of the Regenerative Bioscience Center. And so we do a lot of things with seed grants. And so these are little grants that bring people together that maybe don't collaborate within the Center. And they get together and they work on a project that ultimately turns into something much greater. And so leads to maybe a National Institutes of Health level grant where we're looking for a treatment for cancer. We also do a lot of programs where we're trying to connect undergraduate students with laboratories. So we're trying to get undergraduates into the lab as freshmen or sophomores to learn about the scientific process, to learn different scientific techniques. And many of our students go on to vet school or med school. And so it really helps those students get a better understanding of the scientific process. So I lead the undergraduate research program. So we do a lot of outreach programs like that as part of the executive committee.

Jordan Powers: 7:44

And I want to kind of touch on one thing you just said about leading the undergraduate research program. What would you say to a potential undergrad student? Or maybe someone who's not even a student at UGA yet, who has that interest? You know, going back to four-year-old Dr. West who has this interest in biology?

Franklin West: 7:58

Yeah, no, I think that's really important, to try different things, especially in college, right? So many of us come in, and we have kind of an idea of what we want to do. Our mom and dad probably told us, Oh, you want to be a dentist or you want to be a doctor. In fact, most of my undergraduate students have no idea how to become a scientist, right? In air quotes here. Because they haven't been exposed to that, right? They, as children, or even as adults, you get sick, you go to the doctor, you need your teeth cleaned, you go to the dentist, you don't really interact with scientists too heavily, you may hear about it on CNN or something of the like, but in class, I try to directly encourage them to participate, I say, hey, this will help you also get into med school or vet school because they're looking for those types of experiences. But beyond that, really, it'll teach you about the different therapeutics that you're going to come to use as a medical doctor. And so you'll have a deeper understanding of the science behind these types of treatments. And so many of the students that do these experiences, ultimately discover that, yeah, med school is cool, but really, I should be going to graduate school and become a, you know, regenerative biologist or a cell biologist. And so a lot of the students that come in thinking they want to do one thing, and it's just almost due to a lack of exposure, discover that there's so many other things out there to do. And so for the younger kids, one of the things that the Regenerative Bioscience Center is trying to do is actually get into high schools and bring science to them and talk about how we can use regenerative bioscience to help people and we do little projects. So we show them how to isolate DNA and you can visually see DNA of a strawberry on a stick in some of the projects that we do, we do poster presentations and we try to make it interactive and fun. And so we really are trying to get more students at the high school level because I think we need to get to a middle school high school, elementary school and teach students more about science and what it can do. That's one of the outreach missions of our Center as well.

Jordan Powers: 9:58

Wow, I wanna go back to middle school. I never thought in a million years I'd say that.

Everyone: 10:04

[laughter]

Franklin West: 10:04

Oh no!

Emily Davenport: 10:05

I never had those opportunities, I feel like in school, so cool. You mentioned encouraging collaboration and the RBC is collaborative across departments. Can you share or a little bit more about how those departments are working towards the Center's mission?

Franklin West: 10:18

Yes. So many of the problems that the Regenerative Bioscience Center scientists are tackling are some of the biggest problems in the world, right? We're trying to help people with stroke, which is the second leading cause of death. We're interested in traumatic brain injury, cancer. So we're tackling these major problems. And no one scientist has the entire skill set in order to tackle these problems. And so I'll take our lab, for example. So we're interested in developing stem cell therapies for stroke. And so I have the biology piece covered as a stem cell biologist by training, but a lot of the things that we do is, for example, we'll transplant our cells and then we want to track them in the brain and see how that leads to a decrease in injury in the brain. And so as part of that I collaborate with a physicist, and he does all the MRI analysis on it. And then, after that, we want to see how does that improve functional outcome? So does it improve learning, memory, motor function, and so we work with experts in motor function, to see how these stem cells improve those types of outcomes. And so that's three different groups. And then we also work with a pathologist in the vet school and a neurosurgeon in the vet school. And so that's five labs coming together to work on one project. And that's just one example of collaboration, in the RBC, so we're doing large scale activities.

Emily Davenport: 11:48

Can you talk more about the work that the RBC is doing and how it makes an impact locally, nationally, and internationally?

Franklin West: 11:54

Right. So this goes back to the fact that we are trying to tackle some of the world's biggest problems. So, things like stroke, stroke is the second leading cause of death worldwide. In the United States it's the fifth leading cause of death. And, in fact, Georgia is at the epicenter of the stroke belt. And so we have higher incidences of stroke in the southeast. And it has a lot to do with diet and good southern cooking, right? And so, strokes are caused by blockages in the blood vessel leading to the loss of blood flow in the brain. And so many of these patients are severely disabled after a stroke, they have problems dressing themselves in the morning, feeding themselves, learning and memory problems. So it's a pretty big deal here in the south. And internationally. Traumatic brain injury is another big condition, especially with the wars in Iraq and Afghanistan, it was actually the signature injury for U.S. soldiers that were injured in Afghanistan and Iraq. And so it has major implications.

Emily Davenport: 12:56

You're investigating the use of stem cell treatment for stroke patients. So tell us more about what that means.

Franklin West: 13:03

So we have just completed a major study with Jin Xie in the chemistry department and a number of other faculty members on campus. And so, what we did is we did a study earlier on where we just transplanted stem cells, and our stroke animal model. And those stem cells performed phenomenally. So they were able to turn into neurons and astrocytes and oligodendrocytes. And so these are the critical neural cells in the brain, right. And so they're able to replace those cells, which is important, because many times after stroke, you have a lesion or region where there's no tissue, so the tissue is completely absent or it's damaged. And so the idea is by replacing those tissues, you're ultimately going to be able to restore things like motor function, so you're able to dress yourself in the morning or feed yourself. And so in addition to that, we discovered that our stem cells produce a number of neuroprotective and regenerative factors. And so these are going to be things like, brain derived neurotrophic factor, and they actually prevent tissue from dying. And they also promote natural regeneration processes. So our stem cells that we transplant actually communicate with naturally found stem cells in the brain, and more than tripled the number of natural stem cells in the brain and their response and migration activity to the injury site. And in addition to that, they improved cerebral blood flow. And so we know that those cells produce something called veg F, which is involved in stabilizing blood networks, blood vasculature in the brain, and also promotes vascularization in the brain. And so this is a big deal in stroke, because the cause of stroke is the blockage of that blood vessel. So there's a loss of perfusion, so blood flow in that region. So loss of glucose and oxygen, and so this tissue dies. So if you can actually reverse that process, it's a big deal. And so that was our first study earlier on. And this recent study that we just published on last month, we built upon that initial work, because one of the things that we discovered is we were transplanting 10 million stem cells into the brain, but many of them died. And it kind of makes sense because we're transplanting these cells into what we call an extremely cytotoxic environment. So an environment that's very toxic, and it kills a lot of the cells because there's a lot of free radicals floating around that destroy DNA, RNA, lipids and things.

Sound Effect: 15:32

[chime]

Emily Davenport: 15:32

Free radicals are unstable molecules that build up in cells and can cause damage to other molecules like DNA and proteins. This damage may increase the risk of cancer or other diseases in the body.

Sound Effect: 15:44

[chime]

Franklin West: 15:45

There's an inflammatory response. And so what we did with Jin Xie's group in chemistry is we developed a nanoparticle that we could deliver before we delivered the stem cells. And that nanoparticle carried something called Tanshinone IIA, and it's anti-inflammatory, it's anti-oxidative, so it quelled that environment and made it more accepting for our stem cells. And so we transplanted our neural stem cells into the brain. And it improves survivability and ultimately improved overall recovery of the animal. So everything from smaller tissue damage, decreased tissue loss, to just improved neurological scores. And that last part about improved neurological scores is probably the most important piece, at least clinically speaking, because we show that it improved the ability of animals to stand. So they didn't need to stand with assistance. And so if you think of grandparents that have had stroke, so some of them aren't going to be able to stand or they're going to need a walker or a cane. When you got the treatment, in theory, if we're translating this to people, right, they wouldn't need a walker or a cane. And so we saw improvements in those types of functional outcomes. Ability to feed themselves, so we look at, you know, can they feed themselves? Do they need assistance? Same thing in humans, you know, is that person going to need assistance for the rest of their life to feed themselves or not? And so we saw that in our model system and hopefully it translates to people in a real world way.

Jordan Powers: 17:12

And we actually at the college, put out a story on the nanoparticle components. So we'll definitely link that story in the show notes for our listeners. Following up on that question, we know that the RBC team recently received support from the National Institutes of Health for your traumatic brain injury research. First off, congratulations.

Franklin West: 17:28

Thank you.

Jordan Powers: 17:29

It's wonderful that that work is being supported. Can you talk a little bit more about what that means for RBC and how it will affect the public?

Franklin West: 17:36

Yeah, definitely. So the proposals that we're looking at with the National Institutes of Health focus on two areas, the first area is looking at spontaneous recovery from traumatic brain injury. And we're focusing on pediatric traumatic brain injury, which is kind of a surprise to most people. So about a third of all traumatic brain injuries occur in children, I think anyone that has kids has experienced some scares, where perhaps they fell out of a high chair or off the back of a couch, because kids are always doing stuff. But my daughter actually participates in gymnastics, and she does these backflips on a beam. And every now and again, she kind of comes off. And so kids are typically participating in potentially dangerous activities just because they're kids, right. And so that's why we have so many traumatic brain injury cases in children. And it's quite insidious, because you can imagine survivors of traumatic brain injury, at three have to live with those types of deficits for the rest of their life. Many of them have problems with learning and memory. So they have problems in school, they have behavior problems, so things like abnormal fear, anxiety, stress, almost like PTSD-like symptoms. So post traumatic stress disorder, and many of them also have motor function problems. So they're never going to be able to be on the cheerleading squad or play football. And so it really affects these kids significantly. And so one of the things that we're doing is we're looking at neuroplasticity, and so about 25% of patients that suffer severe or moderate traumatic brain injury to seem to spontaneously recover. And it's almost undiscernible if they have a traumatic brain injury. And so the question becomes, well, what makes those patients different, versus the other 75% that are going to be negatively affected, in some sort of dramatic way. And so what we're doing, we've teamed up with Qun Zhao, he's in the physics department. And we're looking at brain plasticity, and also cognitive reserves. And so there's a little bit of science there for you. But basically, what that means is, we are looking at how the brain communicates with itself. So if you're performing a task, let's say you want to pick up a glass of water, first you have to, your visual network in the brain has to see the glass of water, say, "Okay, we're going to pick that up." And then it actually has to communicate and plan to pick it up and then tell your arm to extend, wrap your fingers around the glass, bring it towards your mouth, open your mouth, and then swallow, right and so this is a highly complex task that requires coordination between five, six different centers in the brain, roughly speaking. And so how does that happen? So, in our traumatic brain injury studies, we're studying how it happens, or comparable or more simple tasks, how that happens before the injury, and then after the injury, and so does the brain re-network, and then does it recruit other parts of the brain to, like, compensate for it. And we're also looking at different types of traumatic brain injury. So there's mild, moderate, severe and so, mild traumatic brain injuries are what football players experience most of the time on the field when they're hitting their helmets together. And so associated with like CTE, so CTE is chronic traumatic encephalopathy. And so basically, this occurs when there's a repeated jarring to the brain. And so you end up with micro injuries in the brain. In fact, they're so small, that you can't detect CTE using traditional modality. So things like magnetic resonance imaging, so MRI or CT scans, football players that are diagnosed with CTE can only be diagnosed post mortem. So actually, once they remove the brain from the skull, but it's basically from all the impacts or the forces generated that are damaging white matter and leading to microbleeds in the brain and the like. And then severe is going to be something more like penetrating traumatic brain injury. And so the idea is that with a mild traumatic brain injury, maybe the brain tissue is there, and it can still do its job, but it's just not as fast or as efficient. But what happens to the same area if it no longer exists, which is like what would happen in a severe traumatic brain injury? So does it recruit new brain centers? Does it actually strengthen connections between other parts of the brain to kind of pick up the task? And so those are the kinds of questions we're addressing with the first part of our NIH study. The other part of the study is, we're actually developing a therapeutic. And so this is with Aruna Biomedical. So a company that Steve Stice, my mentor, started up a number of years ago. And what they've discovered is something really amazing. They're called extracellular vesicles, or EVs, in some cases. Our work is done in the past, in stroke, actually, we have shown that EVs lead to reduced lesion size, so injuries in the brain, they also lead to decrease intracerebral hemorrhaging, so bleeding in the brain, and significant recovery of motor function and other functional outcomes. And so that was in stroke. And it works by decreasing inflammation, a number of other mechanisms. And so the thought was, well, this works so well in stroke, that it's almost to a point where it's going into human clinical trials. And so that's what Aruna is doing is taking that to human clinical trials. So the question is, well, if it's got the same therapeutic function and stroke, let's apply it to traumatic brain injury. And so that's what we're doing now in that space. So we're starting those studies up pretty soon.

Jordan Powers: 23:12

As colleagues of the College of Agricultural and Environmental Sciences, can you tell us how agriculture relates to the work you're doing at RBC?

Franklin West: 23:20

I get asked that question a lot. And what I tell everyone is that farmers have strokes as well. And so ultimately, we're helping farmers that do have strokes or they have children that have traumatic brain injuries. And so we may not be helping grow corn, but we are definitely helping them with their health issues long term. So. I wish I could say we're growing soybeans or something. It's hard to link those two.

Jordan Powers: 23:44

Indeed.

Emily Davenport: 23:45

I think maybe too, tying in your work with pigs might also be a part of the College of Ag and Environmental Sciences?

Franklin West: 23:52

Yeah, so all of our research is actually done in pig models. And the reason for that is, anatomically and physiologically, pigs are more representative of what happens in humans. And so, let's talk about stroke for example. There's been over 700 human clinical trials based on rodent data. There are only two FDA-approved treatments. And so that's a massive failure to translate from basic science to the clinic. So we spent billions of dollars coming up with amazing treatments for stroke in rats and mice. So any mouse that ever has a stroke, we have them fully covered.

Jordan Powers: 24:33

They're set.

Everyone: 24:33

[laughter]

Franklin West: 24:34

They are completely set. It's the people that are in trouble, though, because in fact, about 85% of stroke patients still can't get those two FDA approved treatments, because of other limitations. So we just don't have a treatment for the vast majority of stroke patients. And so there's been a number of groups that have tried to evaluate, "why are we failing to translate?" Because you can imagine we've been looking at stroke for over 100 years trying to come up with treatments. And one of the big things is we're studying it in mice and they're just not people. And so pigs have similar brain structure. So we call it gyrencephalic, and that just means that they have gyri, so ridges in the brain, and the reason that's important as it affects how the brain communicates within itself. It also, when we talk about pig brains and human brains and rodent brains, the human brain has more white matter than rodent brains. And so white matter responds and recovers differently from stroke than gray matter. And so, human's brains are more than 60% white matter, while rodent brains are less than 15% white matter. And so those are the kinds of the reasons that we're using the pig model for, because they're just more comparable. So we think we're going to get more human realistic results, if you will. Traumatic brain injury is the exact same story, so size of brain. And also because we're pediatric, we're interested in brain development and how traumatic brain injury affects brain development. And pig brains actually develop in a way that's more similar than rodent brains. So again, more comparable to humans. And so things like growth spurts, myelination of the brain, so the development of that white matter. So those things are critically important. And also, we're excited about things like nutrition and how that affects traumatic brain injury. And so we're able to feed them different diets, and pig digestion and nutrition, because they're omnivores is more similar to humans. And so again, it's more comparable. And one study that, this is a side note, I guess, we're we're really excited about we're doing a study with Jesse Schank's lab. He's in the vet school here. And he studies alcoholism. And so we were interested in looking at traumatic brain injury, and how it increases addictive behavior, and specifically to alcohol. So a lot of soldiers come back and become addicted to alcohol or opioids. And so the reason we're interested in the pig is rodents innately are not excited about alcohol, they don't like the taste, they don't like the feeling. However, we discovered that pigs enjoy drinking just as much as you and I do. So.[laughs]

Jordan Powers: 27:11

I will never look at a pig the same way again.

Everyone: 27:13

[laughter]

Emily Davenport: 27:13

Right?

Franklin West: 27:15

There you go. There you go. So now we have a pig model of alcoholism as well.

Emily Davenport: 27:19

Wow.

Jordan Powers: 27:20

Well, that might be the takeaway. But, if our listeners could only take away one thing from this conversation today, what do you want them to know about the RBC?

Franklin West: 27:29

So what I would really like them to know is that the Regenerative Bioscience Center is committed again to solving the world's biggest problems. And we're doing that from the very basic science all the way to human clinical trials. And so we've got great work done by researchers like Rachel Galbraith, and she's studying the very molecular mechanisms of regeneration. So she works in an excellent animal model called planarian. So, it's a worm, and what she's shown is you can cut them in half, and one worm now becomes two. And the question becomes, "well, how did that other half of the worm regenerate an entire brain or regenerate other internal organs?" And so, being able to learn the basic principles of tissue regeneration, and then hopefully be able to apply it to, you know, soldiers that have amputated limbs or something of the like, and so she's looking at the basic mechanisms. Then we have other researchers like Jarrod Call, who's looking at things like volumetric muscle loss. So, going back to soldiers that have been injured in Afghanistan, a large chunk of tissue is lost from their calf muscle, for example. So the question is, "how do you help those soldiers recover their ability to to walk and run?" And so that tissue is completely gone? Well he's looking at mitochondria, and how you're able to ramp up the mitochondria's function. So they're the powerhouse of the cell, right? And so they produce the energy, ATP, right? So how do you ramp up their function so they can compensate? And so, and then he's also doing some exciting things, looking at rehabilitation. I've talked a lot about some really high end science, right, stem cell therapies and hydrogels and things of that nature. But, I mean, there's really basic things out there like, well, does exercise improve brain recovery after traumatic brain injury or muscle loss? And so he's looking at some of those things that you can deploy now; they're not 10 years away, something that you can actually apply in the hospital that are well tolerated today. And so he's asking basic questions. And then people like Steve Stice, who is taking his neural stem cell extracellular vesicles into human clinical trials. And so we have everything from A to Z in our pipeline and I'm really excited about the work that we're doing.

Jordan Powers: 29:47

Dr. West, thank you so much for joining us today. This was an engaging, enlightening conversation. Certainly, I think we can dive deeper on so many of these topics. But in lieu of honoring your time today, we'll let you go. But thank you for being with us this afternoon.

Franklin West: 30:03

Thank you so much for inviting me, it was fun.

Emily Davenport: 30:06

Thanks for listening to "Cultivating Curiosity," a podcast produced by the UGA College of Agricultural and Environmental Sciences. A special thanks to Mason McClintock for our music and sound effects. Find more episodes wherever you get your podcasts.