December 12, 2022 • 30 mins
We spoke with Franklin West, professor in the CAES Department of Animal and Dairy Science, executive committee member of the UGA Regenerative Bioscience Center (RBC) and leading expert in stem cell biology research. From stem cell reprogramming to therapies for traumatic brain injuries (TBI) and stroke, learn how RBC researchers are advancing healthy living through bioscience.
Resources:
Learn more about the new regenerative bioscience major offered by CAES at UGA.
A link to the Nobel Peace Prize-winning stem cell research
Read the news story about stroke therapy.
Learn more about the recent NIH grant for TBI research.
Edited by Carly Mirabile
Produced by Jordan Powers, Emily Davenport, Carly Mirabile
Music and sound effects by Mason McClintock, an Athens-based singer, songwriter and storyteller who creates innovative soul-pop music that transcends traditional genre boundaries. Hailing from small-town Southeast Georgia, Mason's influences range from the purest pop to the most powerful gospel. Mason is a former Georgia 4-H'er and a recent University of Georgia graduate! Listen to his music on Spotify.
Get social with us!
Follow CAES on Facebook, Twitter, Instagram and LinkedIn and check out UGA Extension on on Facebook, Twitter, Instagram and LinkedIn for the latest updates.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Sound Effect (00:00):
[music]
Emily Davenport (00:01):
Welcome to "Cultivating Curiosity," where
we get down and dirty with theexperts on all the ways science
and agriculture touch our lives,from what we eat to how we live.
I'm Emily Davenport.
Jordan Powers (00:12):
And I'm Jordan Powers. And we're from the
University of Georgia's Collegeof Agricultural and
Environmental Sciences.
Sound Effect (00:19):
[chime]
Jordan Powers (00:21):
So we are here today with Dr. Franklin West,
Professor in the CAES,Department of Animal and Dairy
Science and executive committeemember of the UGA Regenerative
Bioscience Center. Dr. West,thank you for joining us today.
Franklin West (00:34):
Thank you for inviting me. I'm excited to be
here and talk about what we'redoing.
Jordan Powers (00:37):
Absolutely. Well, as we get started, can you tell
us a little bit about yourbackground? And what drew you
into Animal and Dairy Science?
Franklin West (00:43):
Yes, well, I've always been really excited about
biology. So, my dad was in themilitary, and we lived in Italy.
And I remember, as afour-year-old, my father helped
me put together a net and wewould go outside to the field
next to our house. And we wouldcollect crickets and hornets and
all kinds of things. And we'dput them in a jar and observe
them for a couple of days andtake notes on their behaviors.
(01:06):
And then we'd let them go theday after. So that kind of
started my love with biology ingeneral. And since then, I was
really excited about science.
And so in college, I actuallydid a lot of research with a
gentleman named Dr. LawrenceBlumer, and Morehouse in
Atlanta. And we studied thingslike mate choice and bean
beatles. And then ultimately, itled to an internship at
(01:28):
Princeton University with JeanneAltman. And we were studying
yellow baboons. And I got to goon a trip to Kenya. And so it
was really exciting. We werestudying yellow baboons, and
their mate choice and howdrought affected their
hierarchy. And so I just reallyhave been excited about science
since the beginning, so tospeak, so.
Jordan Powers (01:50):
And what specifically drew you into
Animal and Dairy Science?
Franklin West (01:53):
So because of those earlier experiences, I was
excited about ecology.
Sound Effect (01:57):
[chime]
Emily Davenport (01:58):
Ecology is the study of understanding how
organisms interact with eachother and their environment.
Biotechnology harnessesbiological processes to help in
the development of newtechnology.
[chime]
Franklin West (02:09):
And I wanted to combine that with biotechnology.
And so there's another facultymember in the department who is
my mentor, Steve Stice, he wasinterested in cloning. And so I
was excited about combiningendangered species conservation
with cloning. And so just tokind of put that in perspective,
every year a Florida panther ishit by a car, and so that
(02:32):
narrows the gene pool, andFlorida panthers are at a point
where every time they lose apanther, the gene pool gets
smaller and smaller. Soessentially, they're breeding
cousins to cousins. And so theyhave all kinds of health issues.
And so the thought was, well,maybe you could collect a biopsy
of a piece of tissue from theseFlorida panthers that had just
died, clone those individualsand reintroduce their genetics
(02:54):
back into the population. And soI joined the department as a
graduate student in hislaboratory. And he was doing
some really exciting stuff, inaddition to cloning with stem
cells. And so then we startedplaying with stem cells, for a
variety of reasons. But oneproject was, we're turning stem
cells, human stem cells intosperm. And the idea was, we're
(03:16):
going to be able to use that forinfertile couples. But the way
that ties back into endangeredspecies is, we can now take a
skin cell from that Floridapanther that got hit by the car
and turn that into a stem celland turn that into sperm, and
use that as an assistedreproductive technology. So,
we've been hanging out together,me and Steve, for years. And
(03:37):
these are the kinds of crazythings that go on in our labs.
So.
Jordan Powers (03:41):
Science is amazing.
Everyone (03:43):
[laughter]
Jordan Powers (03:45):
I mean, if you could see our faces right now
like, minds blown.
Everyone (03:48):
[laughter]
Emily Davenport (03:49):
Jaws on the table.
Everyone (03:53):
[laughter]
Emily Davenport (03:53):
So you mentioned stem cells. Can you
share more with our audienceabout what that means?
Franklin West (03:58):
All right, so our lab is a stem cell laboratory.
And I know at one point stemcells were highly controversial.
So they were being derived fromembryonic sources. However,
today, we actually get it fromskin cells. So Shinya Yamanaka
in 2006, developed somegroundbreaking technology where
I could actually take a skincell from any patient and add
(04:20):
four to six genes. And thatactually takes that skin cell
all the way back to what we calla pluripotent state. And those
cells are capable of forming anycell type in the body. So
cardiovascular cells, neuralcells, etc. And so we've gotten
around the whole issueassociated with that controversy
by using this technology. Heactually won the Nobel Prize for
(04:42):
it, it's kind of how big it was,right?
Sound Effect (04:44):
[chime]
Jordan Powers (04:45):
We'll put a link to the Nobel Peace Prize-winning
research in the shownotes foryou.
Sound Effect (04:48):
[chime]
Franklin West (04:49):
So these stem cells are capable of turning any
cell type in the body and whatwe do is we take skin cells,
turn them into neural stemcells, then transplant them into
the brain tissue and the neuralstem cells turn into astrocytes
and oligodendrocytes in neurons.
Jordan Powers (05:04):
So you're doing all this work with stem cells
and endangered species. Whatdoes this mean for regenerative
bioscience?
Franklin West (05:10):
Yes. So our lab, we're still excited about
endangered species conservation.
But we have gotten into what'smore traditional, which I don't
think regenerative bioscience istraditional in any sense of the
word. But regenerativebioscience is basically we're
taking different scientificapproaches to enhance tissue
regeneration in the body. And sothere's a number of groups that
(05:31):
are working together to addressa variety of different
conditions. So, for example, JinXie, in the chemistry
department, who we work with,he's using nanoparticles to
deliver signaling factors thatpromote tissue regeneration. And
then we also work with otherlaboratories that are using
hydrogels and differentextracellular matrices to
(05:52):
improve tissue regeneration inthe brain after traumatic brain
injury. So basically,regenerative bioscience is
taking a number of differentscience technologies, combining
them together to promoteendogenous or natural recovery
in the body from Parkinson's,Alzheimer's, to other types of
injuries as well.
Emily Davenport (06:12):
So magic.
Franklin West (06:13):
Basically. It's basically magic.
Everyone (06:15):
[laughter]
Jordan Powers (06:17):
Truly life changing for countless people
though, which is incredible.
Franklin West (06:21):
It is, it is.
Jordan Powers (06:23):
Tell us a little bit about your role with the
Regenerative Bioscience Center.
Franklin West (06:26):
Yeah, so as an executive committee member, what
we do is we try to developdifferent programs to help
foster collaborations betweendifferent members as part of the
Regenerative Bioscience Center.
And so we do a lot of thingswith seed grants. And so these
are little grants that bringpeople together that maybe don't
collaborate within the Center.
(06:48):
And they get together and theywork on a project that
ultimately turns into somethingmuch greater. And so leads to
maybe a National Institutes ofHealth level grant where we're
looking for a treatment forcancer. We also do a lot of
programs where we're trying toconnect undergraduate students
with laboratories. So we'retrying to get undergraduates
into the lab as freshmen orsophomores to learn about the
(07:11):
scientific process, to learndifferent scientific techniques.
And many of our students go onto vet school or med school. And
so it really helps thosestudents get a better
understanding of the scientificprocess. So I lead the
undergraduate research program.
So we do a lot of outreachprograms like that as part of
the executive committee.
Jordan Powers (07:29):
And I want to kind of touch on one thing you
just said about leading theundergraduate research program.
What would you say to apotential undergrad student? Or
maybe someone who's not even astudent at UGA yet, who has that
interest? You know, going backto four-year-old Dr. West who
has this interest in biology?
Franklin West (07:43):
Yeah, no, I think that's really important, to try
different things, especially incollege, right? So many of us
come in, and we have kind of anidea 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. Infact, most of my undergraduate
students have no idea how tobecome a scientist, right? In
air quotes here. Because theyhaven't been exposed to that,
(08:06):
right? They, as children, oreven as adults, you get sick,
you go to the doctor, you needyour teeth cleaned, you go to
the dentist, you don't reallyinteract with scientists too
heavily, you may hear about iton CNN or something of the like,
but in class, I try to directlyencourage them to participate, I
say, hey, this will help youalso get into med school or vet
school because they're lookingfor those types of experiences.
(08:28):
But beyond that, really, it'llteach you about the different
therapeutics that you're goingto come to use as a medical
doctor. And so you'll have adeeper understanding of the
science behind these types oftreatments. And so many of the
students that do theseexperiences, ultimately discover
that, yeah, med school is cool,but really, I should be going to
graduate school and become a,you know, regenerative biologist
(08:51):
or a cell biologist. And so alot of the students that come in
thinking they want to do onething, and it's just almost due
to a lack of exposure, discoverthat there's so many other
things out there to do. And sofor the younger kids, one of the
things that the RegenerativeBioscience Center is trying to
do is actually get into highschools and bring science to
them and talk about how we canuse regenerative bioscience to
(09:14):
help people and we do littleprojects. So we show them how to
isolate DNA and you can visuallysee DNA of a strawberry on a
stick in some of the projectsthat we do, we do poster
presentations and we try to makeit interactive and fun. And so
we really are trying to get morestudents at the high school
level because I think we need toget to a middle school high
(09:35):
school, elementary school andteach students more about
science and what it can do.
That's one of the outreachmissions of our Center as well.
Jordan Powers (09:43):
Wow, I wanna go back to middle school. I never
thought in a million years I'dsay that.
Everyone (09:49):
[laughter]
Franklin West (09:49):
Oh no!
Emily Davenport (09:50):
I never had those opportunities, I feel like
in school, so cool. Youmentioned encouraging
collaboration and the RBC iscollaborative across
departments. Can you share or alittle bit more about how those
departments are working towardsthe Center's mission?
Franklin West (10:04):
Yes. So many of the problems that the
Regenerative Bioscience Centerscientists are tackling are some
of the biggest problems in theworld, right? We're trying to
help people with stroke, whichis the second leading cause of
death. We're interested intraumatic brain injury, cancer.
So we're tackling these majorproblems. And no one scientist
(10:26):
has the entire skill set inorder to tackle these problems.
And so I'll take our lab, forexample. So we're interested in
developing stem cell therapiesfor stroke. And so I have the
biology piece covered as a stemcell biologist by training, but
a lot of the things that we dois, for example, we'll
transplant our cells and then wewant to track them in the brain
(10:48):
and see how that leads to adecrease in injury in the brain.
And so as part of that Icollaborate with a physicist,
and he does all the MRI analysison it. And then, after that, we
want to see how does thatimprove functional outcome? So
does it improve learning,memory, motor function, and so
we work with experts in motorfunction, to see how these stem
(11:12):
cells improve those types ofoutcomes. And so that's three
different groups. And then wealso work with a pathologist in
the vet school and aneurosurgeon in the vet school.
And so that's five labs comingtogether to work on one project.
And that's just one example ofcollaboration, in the RBC, so
we're doing large scaleactivities.
Emily Davenport (11:33):
Can you talk more about the work that the RBC
is doing and how it makes animpact locally, nationally, and
internationally?
Franklin West (11:40):
Right. So this goes back to the fact that we
are trying to tackle some of theworld's biggest problems. So,
things like stroke, stroke isthe second leading cause of
death worldwide. In the UnitedStates it's the fifth leading
cause of death. And, in fact,Georgia is at the epicenter of
the stroke belt. And so we havehigher incidences of stroke in
(12:01):
the southeast. And it has a lotto do with diet and good
southern cooking, right? And so,strokes are caused by blockages
in the blood vessel leading tothe loss of blood flow in the
brain. And so many of thesepatients are severely disabled
after a stroke, they haveproblems dressing themselves in
the morning, feeding themselves,learning and memory problems. So
(12:22):
it's a pretty big deal here inthe south. And internationally.
Traumatic brain injury isanother big condition,
especially with the wars in Iraqand Afghanistan, it was actually
the signature injury for U.S.
soldiers that were injured inAfghanistan and Iraq. And so it
has major implications.
Emily Davenport (12:42):
You're investigating the use of stem
cell treatment for strokepatients. So tell us more about
what that means.
Franklin West (12:49):
So we have just completed a major study with Jin
Xie in the chemistry departmentand a number of other faculty
members on campus. And so, whatwe did is we did a study earlier
on where we just transplantedstem cells, and our stroke
animal model. And those stemcells performed phenomenally. So
(13:09):
they were able to turn intoneurons and astrocytes and
oligodendrocytes. And so theseare the critical neural cells in
the brain, right. And so they'reable to replace those cells,
which is important, because manytimes after stroke, you have a
lesion or region where there'sno tissue, so the tissue is
completely absent or it'sdamaged. And so the idea is by
(13:30):
replacing those tissues, you'reultimately going to be able to
restore things like motorfunction, so you're able to
dress yourself in the morning orfeed yourself. And so in
addition to that, we discoveredthat our stem cells produce a
number of neuroprotective andregenerative factors. And so
these are going to be thingslike, brain derived neurotrophic
(13:50):
factor, and they actuallyprevent tissue from dying. And
they also promote naturalregeneration processes. So our
stem cells that we transplantactually communicate with
naturally found stem cells inthe brain, and more than tripled
the number of natural stem cellsin the brain and their response
(14:10):
and migration activity to theinjury site. And in addition to
that, they improved cerebralblood flow. And so we know that
those cells produce somethingcalled veg F, which is involved
in stabilizing blood networks,blood vasculature in the brain,
and also promotesvascularization in the brain.
And so this is a big deal instroke, because the cause of
(14:32):
stroke is the blockage of thatblood vessel. So there's a loss
of perfusion, so blood flow inthat region. So loss of glucose
and oxygen, and so this tissuedies. So if you can actually
reverse that process, it's a bigdeal. And so that was our first
study earlier on. And thisrecent study that we just
published on last month, webuilt upon that initial work,
(14:54):
because one of the things thatwe discovered is we were
transplanting 10 million stemcells into the brain, but many
of them died. And it kind ofmakes sense because we're
transplanting these cells intowhat we call an extremely
cytotoxic environment. So anenvironment that's very toxic,
and it kills a lot of the cellsbecause there's a lot of free
radicals floating around thatdestroy DNA, RNA, lipids and
(15:16):
things.
Sound Effect (15:17):
[chime]
Emily Davenport (15:18):
Free radicals are unstable molecules that
build up in cells and can causedamage to other molecules like
DNA and proteins. This damagemay increase the risk of cancer
or other diseases in the body.
Sound Effect (15:29):
[chime]
Franklin West (15:30):
There's an inflammatory response. And so
what we did with Jin Xie's groupin chemistry is we developed a
nanoparticle that we coulddeliver before we delivered the
stem cells. And thatnanoparticle carried something
called Tanshinone IIA, and it'santi-inflammatory, it's
anti-oxidative, so it quelledthat environment and made it
(15:53):
more accepting for our stemcells. And so we transplanted
our neural stem cells into thebrain. And it improves
survivability and ultimatelyimproved overall recovery of the
animal. So everything fromsmaller tissue damage, decreased
tissue loss, to just improvedneurological scores. And that
last part about improvedneurological scores is probably
(16:13):
the most important piece, atleast clinically speaking,
because we show that it improvedthe ability of animals to stand.
So they didn't need to standwith assistance. And so if you
think of grandparents that havehad stroke, so some of them
aren't going to be able to standor they're going to need a
walker or a cane. When you gotthe treatment, in theory, if
(16:33):
we're translating this topeople, right, they wouldn't
need a walker or a cane. And sowe saw improvements in those
types of functional outcomes.
Ability to feed themselves, sowe look at, you know, can they
feed themselves? Do they needassistance? Same thing in
humans, you know, is that persongoing to need assistance for the
rest of their life to feedthemselves or not? And so we saw
that in our model system andhopefully it translates to
(16:54):
people in a real world way.
Jordan Powers (16:57):
And we actually at the college, put out a story
on the nanoparticle components.
So we'll definitely link thatstory in the show notes for our
listeners. Following up on thatquestion, we know that the RBC
team recently received supportfrom the National Institutes of
Health for your traumatic braininjury research. First off,
congratulations.
Franklin West (17:13):
Thank you.
Jordan Powers (17:14):
It's wonderful that that work is being
supported. Can you talk a littlebit more about what that means
for RBC and how it will affectthe public?
Franklin West (17:21):
Yeah, definitely.
So the proposals that we'relooking at with the National
Institutes of Health focus ontwo areas, the first area is
looking at spontaneous recoveryfrom traumatic brain injury. And
we're focusing on pediatrictraumatic brain injury, which is
kind of a surprise to mostpeople. So about a third of all
traumatic brain injuries occurin children, I think anyone that
(17:43):
has kids has experienced somescares, where perhaps they fell
out of a high chair or off theback of a couch, because kids
are always doing stuff. But mydaughter actually participates
in gymnastics, and she doesthese backflips on a beam. And
every now and again, she kind ofcomes off. And so kids are
typically participating inpotentially dangerous activities
(18:04):
just because they're kids,right. And so that's why we have
so many traumatic brain injurycases in children. And it's
quite insidious, because you canimagine survivors of traumatic
brain injury, at three have tolive with those types of
deficits for the rest of theirlife. Many of them have problems
with learning and memory. Sothey have problems in school,
(18:25):
they have behavior problems, sothings like abnormal fear,
anxiety, stress, almost likePTSD-like symptoms. So post
traumatic stress disorder, andmany of them also have motor
function problems. So they'renever going to be able to be on
the cheerleading squad or playfootball. And so it really
affects these kidssignificantly. And so one of the
(18:47):
things that we're doing is we'relooking at neuroplasticity, and
so about 25% of patients thatsuffer severe or moderate
traumatic brain injury to seemto spontaneously recover. And
it's almost undiscernible ifthey have a traumatic brain
injury. And so the questionbecomes, well, what makes those
patients different, versus theother 75% that are going to be
(19:09):
negatively affected, in somesort of dramatic way. And so
what we're doing, we've teamedup with Qun Zhao, he's in the
physics department. And we'relooking at brain plasticity, and
also cognitive reserves. And sothere's a little bit of science
there for you. But basically,what that means is, we are
looking at how the braincommunicates with itself. So if
(19:31):
you're performing a task, let'ssay 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 actuallyhas to communicate and plan to
pick it up and then tell yourarm to extend, wrap your fingers
around the glass, bring ittowards your mouth, open your
mouth, and then swallow, rightand so this is a highly complex
(19:54):
task that requires coordinationbetween five, six different
centers in the brain, roughlyspeaking. And so how does that
happen? So, in our traumaticbrain injury studies, we're
studying how it happens, orcomparable or more simple tasks,
how that happens before theinjury, and then after the
injury, and so does the brainre-network, and then does it
(20:17):
recruit other parts of the brainto, like, compensate for it. And
we're also looking at differenttypes of traumatic brain injury.
So there's mild, moderate,severe and so, mild traumatic
brain injuries are what footballplayers experience most of the
time on the field when they'rehitting their helmets together.
And so associated with like CTE,so CTE is chronic traumatic
(20:38):
encephalopathy. And sobasically, this occurs when
there's a repeated jarring tothe brain. And so you end up
with micro injuries in thebrain. In fact, they're so
small, that you can't detect CTEusing traditional modality. So
things like magnetic resonanceimaging, so MRI or CT scans,
football players that arediagnosed with CTE can only be
(21:02):
diagnosed post mortem. Soactually, once they remove the
brain from the skull, but it'sbasically from all the impacts
or the forces generated that aredamaging white matter and
leading to microbleeds in thebrain and the like. And then
severe is going to be somethingmore like penetrating traumatic
brain injury. And so the idea isthat with a mild traumatic brain
(21:24):
injury, maybe the brain tissueis there, and it can still do
its job, but it's just not asfast or as efficient. But what
happens to the same area if itno longer exists, which is like
what would happen in a severetraumatic brain injury? So does
it recruit new brain centers?
Does it actually strengthenconnections between other parts
(21:44):
of the brain to kind of pick upthe task? And so those are the
kinds of questions we'readdressing with the first part
of our NIH study. The other partof the study is, we're actually
developing a therapeutic. And sothis is with Aruna Biomedical.
So a company that Steve Stice,my mentor, started up a number
of years ago. And what they'vediscovered is something really
(22:04):
amazing. They're calledextracellular vesicles, or EVs,
in some cases. Our work is donein the past, in stroke,
actually, we have shown that EVslead to reduced lesion size, so
injuries in the brain, they alsolead to decrease intracerebral
hemorrhaging, so bleeding in thebrain, and significant recovery
(22:26):
of motor function and otherfunctional outcomes. And so that
was in stroke. And it works bydecreasing inflammation, a
number of other mechanisms. Andso the thought was, well, this
works so well in stroke, thatit's almost to a point where
it's going into human clinicaltrials. And so that's what Aruna
is doing is taking that to humanclinical trials. So the question
(22:46):
is, well, if it's got the sametherapeutic function and stroke,
let's apply it to traumaticbrain injury. And so that's what
we're doing now in that space.
So we're starting those studiesup pretty soon.
Jordan Powers (22:57):
As colleagues of the College of Agricultural and
Environmental Sciences, can youtell us how agriculture relates
to the work you're doing at RBC?
Franklin West (23:05):
I get asked that question a lot. And what I tell
everyone is that farmers havestrokes as well. And so
ultimately, we're helpingfarmers that do have strokes or
they have children that havetraumatic brain injuries. And so
we may not be helping grow corn,but we are definitely helping
them with their health issueslong term. So. I wish I could
say we're growing soybeans orsomething. It's hard to link
(23:27):
those two.
Jordan Powers (23:29):
Indeed.
Emily Davenport (23:30):
I think maybe too, tying in your work with
pigs might also be a part of theCollege of Ag and Environmental
Sciences?
Franklin West (23:37):
Yeah, so all of our research is actually done in
pig models. And the reason forthat is, anatomically and
physiologically, pigs are morerepresentative of what happens
in humans. And so, let's talkabout stroke for example.
There's been over 700 humanclinical trials based on rodent
(23:59):
data. There are only twoFDA-approved treatments. And so
that's a massive failure totranslate from basic science to
the clinic. So we spent billionsof dollars coming up with
amazing treatments for stroke inrats and mice. So any mouse that
ever has a stroke, we have themfully covered.
Jordan Powers (24:18):
They're set.
Everyone (24:18):
[laughter]
Franklin West (24:19):
They are completely set. It's the people
that are in trouble, though,because in fact, about 85% of
stroke patients still can't getthose two FDA approved
treatments, because of otherlimitations. So we just don't
have a treatment for the vastmajority of stroke patients. And
so there's been a number ofgroups that have tried to
evaluate, "why are we failing totranslate?" Because you can
(24:42):
imagine we've been looking atstroke for over 100 years trying
to come up with treatments. Andone of the big things is we're
studying it in mice and they'rejust not people. And so pigs
have similar brain structure. Sowe call it gyrencephalic, and
that just means that they havegyri, so ridges in the brain,
and the reason that's importantas it affects how the brain
communicates within itself. Italso, when we talk about pig
(25:06):
brains and human brains androdent brains, the human brain
has more white matter thanrodent brains. And so white
matter responds and recoversdifferently from stroke than
gray matter. And so, human'sbrains are more than 60% white
matter, while rodent brains areless than 15% white matter. And
so those are the kinds of thereasons that we're using the pig
(25:27):
model for, because they're justmore comparable. So we think
we're going to get more humanrealistic results, if you will.
Traumatic brain injury is theexact same story, so size of
brain. And also because we'repediatric, we're interested in
brain development and howtraumatic brain injury affects
brain development. And pigbrains actually develop in a way
that's more similar than rodentbrains. So again, more
(25:51):
comparable to humans. And sothings like growth spurts,
myelination of the brain, so thedevelopment of that white
matter. So those things arecritically important. And also,
we're excited about things likenutrition and how that affects
traumatic brain injury. And sowe're able to feed them
different diets, and pigdigestion and nutrition, because
(26:11):
they're omnivores is moresimilar to humans. And so again,
it's more comparable. And onestudy that, this is a side note,
I guess, we're we're reallyexcited about we're doing a
study with Jesse Schank's lab.
He's in the vet school here. Andhe studies alcoholism. And so we
were interested in looking attraumatic brain injury, and how
it increases addictive behavior,and specifically to alcohol. So
(26:35):
a lot of soldiers come back andbecome addicted to alcohol or
opioids. And so the reason we'reinterested in the pig is rodents
innately are not excited aboutalcohol, they don't like the
taste, they don't like thefeeling. However, we discovered
that pigs enjoy drinking just asmuch as you and I do. So.
[laughs]
Jordan Powers (26:56):
I will never look at a pig the same way again.
Everyone (26:58):
[laughter]
Emily Davenport (26:58):
Right?
Franklin West (27:00):
There you go.
There you go. So now we have apig model of alcoholism as well.
Emily Davenport (27:04):
Wow.
Jordan Powers (27:06):
Well, that might be the takeaway. But, if our
listeners could only take awayone thing from this conversation
today, what do you want them toknow about the RBC?
Franklin West (27:14):
So what I would really like them to know is that
the Regenerative BioscienceCenter is committed again to
solving the world's biggestproblems. And we're doing that
from the very basic science allthe way to human clinical
trials. And so we've got greatwork done by researchers like
Rachel Galbraith, and she'sstudying the very molecular
(27:34):
mechanisms of regeneration. Soshe works in an excellent animal
model called planarian. So, it'sa worm, and what she's shown is
you can cut them in half, andone worm now becomes two. And
the question becomes, "well, howdid that other half of the worm
regenerate an entire brain orregenerate other internal
organs?" And so, being able tolearn the basic principles of
(27:58):
tissue regeneration, and thenhopefully be able to apply it
to, you know, soldiers that haveamputated limbs or something of
the like, and so she's lookingat the basic mechanisms. Then we
have other researchers likeJarrod Call, who's looking at
things like volumetric muscleloss. So, going back to soldiers
that have been injured inAfghanistan, a large chunk of
tissue is lost from their calfmuscle, for example. So the
(28:22):
question is, "how do you helpthose soldiers recover their
ability to to walk and run?" Andso that tissue is completely
gone? Well he's looking atmitochondria, and how you're
able to ramp up themitochondria's function. So
they're the powerhouse of thecell, right? And so they produce
the energy, ATP, right? So howdo you ramp up their function so
(28:44):
they can compensate? And so, andthen he's also doing some
exciting things, looking atrehabilitation. I've talked a
lot about some really high endscience, right, stem cell
therapies and hydrogels andthings of that nature. But, I
mean, there's really basicthings out there like, well,
does exercise improve brainrecovery after traumatic brain
(29:05):
injury or muscle loss? And sohe's looking at some of those
things that you can deploy now;they're not 10 years away,
something that you can actuallyapply in the hospital that are
well tolerated today. And sohe's asking basic questions. And
then people like Steve Stice,who is taking his neural stem
cell extracellular vesicles intohuman clinical trials. And so we
(29:26):
have everything from A to Z inour pipeline and I'm really
excited about the work thatwe're doing.
Jordan Powers (29:32):
Dr. West, thank you so much for joining us
today. This was an engaging,enlightening conversation.
Certainly, I think we can divedeeper on so many of these
topics. But in lieu of honoringyour time today, we'll let you
go. But thank you for being withus this afternoon.
Franklin West (29:48):
Thank you so much for inviting me, it was fun.
Emily Davenport (29:52):
Thanks for listening to "Cultivating
Curiosity," a podcast producedby the UGA College of
Agricultural and EnvironmentalSciences. A special thanks to
Mason McClintock for our musicand sound effects. Find more
episodes wherever you get yourpodcasts.
[music]
Emily Davenport (00:01):
Welcome to "Cultivating Curiosity," where
we get down and dirty with theexperts on all the ways science
and agriculture touch our lives,from what we eat to how we live.
I'm Emily Davenport.
Jordan Powers (00:12):
And I'm Jordan Powers. And we're from the
University of Georgia's Collegeof Agricultural and
Environmental Sciences.
Sound Effect (00:19):
[chime]
Jordan Powers (00:21):
So we are here today with Dr. Franklin West,
Professor in the CAES,Department of Animal and Dairy
Science and executive committeemember of the UGA Regenerative
Bioscience Center. Dr. West,thank you for joining us today.
Franklin West (00:34):
Thank you for inviting me. I'm excited to be
here and talk about what we'redoing.
Jordan Powers (00:37):
Absolutely. Well, as we get started, can you tell
us a little bit about yourbackground? And what drew you
into Animal and Dairy Science?
Franklin West (00:43):
Yes, well, I've always been really excited about
biology. So, my dad was in themilitary, and we lived in Italy.
And I remember, as afour-year-old, my father helped
me put together a net and wewould go outside to the field
next to our house. And we wouldcollect crickets and hornets and
all kinds of things. And we'dput them in a jar and observe
them for a couple of days andtake notes on their behaviors.
(01:06):
And then we'd let them go theday after. So that kind of
started my love with biology ingeneral. And since then, I was
really excited about science.
And so in college, I actuallydid a lot of research with a
gentleman named Dr. LawrenceBlumer, and Morehouse in
Atlanta. And we studied thingslike mate choice and bean
beatles. And then ultimately, itled to an internship at
(01:28):
Princeton University with JeanneAltman. And we were studying
yellow baboons. And I got to goon a trip to Kenya. And so it
was really exciting. We werestudying yellow baboons, and
their mate choice and howdrought affected their
hierarchy. And so I just reallyhave been excited about science
since the beginning, so tospeak, so.
Jordan Powers (01:50):
And what specifically drew you into
Animal and Dairy Science?
Franklin West (01:53):
So because of those earlier experiences, I was
excited about ecology.
Sound Effect (01:57):
[chime]
Emily Davenport (01:58):
Ecology is the study of understanding how
organisms interact with eachother and their environment.
Biotechnology harnessesbiological processes to help in
the development of newtechnology.
[chime]
Franklin West (02:09):
And I wanted to combine that with biotechnology.
And so there's another facultymember in the department who is
my mentor, Steve Stice, he wasinterested in cloning. And so I
was excited about combiningendangered species conservation
with cloning. And so just tokind of put that in perspective,
every year a Florida panther ishit by a car, and so that
(02:32):
narrows the gene pool, andFlorida panthers are at a point
where every time they lose apanther, the gene pool gets
smaller and smaller. Soessentially, they're breeding
cousins to cousins. And so theyhave all kinds of health issues.
And so the thought was, well,maybe you could collect a biopsy
of a piece of tissue from theseFlorida panthers that had just
died, clone those individualsand reintroduce their genetics
(02:54):
back into the population. And soI joined the department as a
graduate student in hislaboratory. And he was doing
some really exciting stuff, inaddition to cloning with stem
cells. And so then we startedplaying with stem cells, for a
variety of reasons. But oneproject was, we're turning stem
cells, human stem cells intosperm. And the idea was, we're
(03:16):
going to be able to use that forinfertile couples. But the way
that ties back into endangeredspecies is, we can now take a
skin cell from that Floridapanther that got hit by the car
and turn that into a stem celland turn that into sperm, and
use that as an assistedreproductive technology. So,
we've been hanging out together,me and Steve, for years. And
(03:37):
these are the kinds of crazythings that go on in our labs.
So.
Jordan Powers (03:41):
Science is amazing.
Everyone (03:43):
[laughter]
Jordan Powers (03:45):
I mean, if you could see our faces right now
like, minds blown.
Everyone (03:48):
[laughter]
Emily Davenport (03:49):
Jaws on the table.
Everyone (03:53):
[laughter]
Emily Davenport (03:53):
So you mentioned stem cells. Can you
share more with our audienceabout what that means?
Franklin West (03:58):
All right, so our lab is a stem cell laboratory.
And I know at one point stemcells were highly controversial.
So they were being derived fromembryonic sources. However,
today, we actually get it fromskin cells. So Shinya Yamanaka
in 2006, developed somegroundbreaking technology where
I could actually take a skincell from any patient and add
(04:20):
four to six genes. And thatactually takes that skin cell
all the way back to what we calla pluripotent state. And those
cells are capable of forming anycell type in the body. So
cardiovascular cells, neuralcells, etc. And so we've gotten
around the whole issueassociated with that controversy
by using this technology. Heactually won the Nobel Prize for
(04:42):
it, it's kind of how big it was,right?
Sound Effect (04:44):
[chime]
Jordan Powers (04:45):
We'll put a link to the Nobel Peace Prize-winning
research in the shownotes foryou.
Sound Effect (04:48):
[chime]
Franklin West (04:49):
So these stem cells are capable of turning any
cell type in the body and whatwe do is we take skin cells,
turn them into neural stemcells, then transplant them into
the brain tissue and the neuralstem cells turn into astrocytes
and oligodendrocytes in neurons.
Jordan Powers (05:04):
So you're doing all this work with stem cells
and endangered species. Whatdoes this mean for regenerative
bioscience?
Franklin West (05:10):
Yes. So our lab, we're still excited about
endangered species conservation.
But we have gotten into what'smore traditional, which I don't
think regenerative bioscience istraditional in any sense of the
word. But regenerativebioscience is basically we're
taking different scientificapproaches to enhance tissue
regeneration in the body. And sothere's a number of groups that
(05:31):
are working together to addressa variety of different
conditions. So, for example, JinXie, in the chemistry
department, who we work with,he's using nanoparticles to
deliver signaling factors thatpromote tissue regeneration. And
then we also work with otherlaboratories that are using
hydrogels and differentextracellular matrices to
(05:52):
improve tissue regeneration inthe brain after traumatic brain
injury. So basically,regenerative bioscience is
taking a number of differentscience technologies, combining
them together to promoteendogenous or natural recovery
in the body from Parkinson's,Alzheimer's, to other types of
injuries as well.
Emily Davenport (06:12):
So magic.
Franklin West (06:13):
Basically. It's basically magic.
Everyone (06:15):
[laughter]
Jordan Powers (06:17):
Truly life changing for countless people
though, which is incredible.
Franklin West (06:21):
It is, it is.
Jordan Powers (06:23):
Tell us a little bit about your role with the
Regenerative Bioscience Center.
Franklin West (06:26):
Yeah, so as an executive committee member, what
we do is we try to developdifferent programs to help
foster collaborations betweendifferent members as part of the
Regenerative Bioscience Center.
And so we do a lot of thingswith seed grants. And so these
are little grants that bringpeople together that maybe don't
collaborate within the Center.
(06:48):
And they get together and theywork on a project that
ultimately turns into somethingmuch greater. And so leads to
maybe a National Institutes ofHealth level grant where we're
looking for a treatment forcancer. We also do a lot of
programs where we're trying toconnect undergraduate students
with laboratories. So we'retrying to get undergraduates
into the lab as freshmen orsophomores to learn about the
(07:11):
scientific process, to learndifferent scientific techniques.
And many of our students go onto vet school or med school. And
so it really helps thosestudents get a better
understanding of the scientificprocess. So I lead the
undergraduate research program.
So we do a lot of outreachprograms like that as part of
the executive committee.
Jordan Powers (07:29):
And I want to kind of touch on one thing you
just said about leading theundergraduate research program.
What would you say to apotential undergrad student? Or
maybe someone who's not even astudent at UGA yet, who has that
interest? You know, going backto four-year-old Dr. West who
has this interest in biology?
Franklin West (07:43):
Yeah, no, I think that's really important, to try
different things, especially incollege, right? So many of us
come in, and we have kind of anidea 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. Infact, most of my undergraduate
students have no idea how tobecome a scientist, right? In
air quotes here. Because theyhaven't been exposed to that,
(08:06):
right? They, as children, oreven as adults, you get sick,
you go to the doctor, you needyour teeth cleaned, you go to
the dentist, you don't reallyinteract with scientists too
heavily, you may hear about iton CNN or something of the like,
but in class, I try to directlyencourage them to participate, I
say, hey, this will help youalso get into med school or vet
school because they're lookingfor those types of experiences.
(08:28):
But beyond that, really, it'llteach you about the different
therapeutics that you're goingto come to use as a medical
doctor. And so you'll have adeeper understanding of the
science behind these types oftreatments. And so many of the
students that do theseexperiences, ultimately discover
that, yeah, med school is cool,but really, I should be going to
graduate school and become a,you know, regenerative biologist
(08:51):
or a cell biologist. And so alot of the students that come in
thinking they want to do onething, and it's just almost due
to a lack of exposure, discoverthat there's so many other
things out there to do. And sofor the younger kids, one of the
things that the RegenerativeBioscience Center is trying to
do is actually get into highschools and bring science to
them and talk about how we canuse regenerative bioscience to
(09:14):
help people and we do littleprojects. So we show them how to
isolate DNA and you can visuallysee DNA of a strawberry on a
stick in some of the projectsthat we do, we do poster
presentations and we try to makeit interactive and fun. And so
we really are trying to get morestudents at the high school
level because I think we need toget to a middle school high
(09:35):
school, elementary school andteach students more about
science and what it can do.
That's one of the outreachmissions of our Center as well.
Jordan Powers (09:43):
Wow, I wanna go back to middle school. I never
thought in a million years I'dsay that.
Everyone (09:49):
[laughter]
Franklin West (09:49):
Oh no!
Emily Davenport (09:50):
I never had those opportunities, I feel like
in school, so cool. Youmentioned encouraging
collaboration and the RBC iscollaborative across
departments. Can you share or alittle bit more about how those
departments are working towardsthe Center's mission?
Franklin West (10:04):
Yes. So many of the problems that the
Regenerative Bioscience Centerscientists are tackling are some
of the biggest problems in theworld, right? We're trying to
help people with stroke, whichis the second leading cause of
death. We're interested intraumatic brain injury, cancer.
So we're tackling these majorproblems. And no one scientist
(10:26):
has the entire skill set inorder to tackle these problems.
And so I'll take our lab, forexample. So we're interested in
developing stem cell therapiesfor stroke. And so I have the
biology piece covered as a stemcell biologist by training, but
a lot of the things that we dois, for example, we'll
transplant our cells and then wewant to track them in the brain
(10:48):
and see how that leads to adecrease in injury in the brain.
And so as part of that Icollaborate with a physicist,
and he does all the MRI analysison it. And then, after that, we
want to see how does thatimprove functional outcome? So
does it improve learning,memory, motor function, and so
we work with experts in motorfunction, to see how these stem
(11:12):
cells improve those types ofoutcomes. And so that's three
different groups. And then wealso work with a pathologist in
the vet school and aneurosurgeon in the vet school.
And so that's five labs comingtogether to work on one project.
And that's just one example ofcollaboration, in the RBC, so
we're doing large scaleactivities.
Emily Davenport (11:33):
Can you talk more about the work that the RBC
is doing and how it makes animpact locally, nationally, and
internationally?
Franklin West (11:40):
Right. So this goes back to the fact that we
are trying to tackle some of theworld's biggest problems. So,
things like stroke, stroke isthe second leading cause of
death worldwide. In the UnitedStates it's the fifth leading
cause of death. And, in fact,Georgia is at the epicenter of
the stroke belt. And so we havehigher incidences of stroke in
(12:01):
the southeast. And it has a lotto do with diet and good
southern cooking, right? And so,strokes are caused by blockages
in the blood vessel leading tothe loss of blood flow in the
brain. And so many of thesepatients are severely disabled
after a stroke, they haveproblems dressing themselves in
the morning, feeding themselves,learning and memory problems. So
(12:22):
it's a pretty big deal here inthe south. And internationally.
Traumatic brain injury isanother big condition,
especially with the wars in Iraqand Afghanistan, it was actually
the signature injury for U.S.
soldiers that were injured inAfghanistan and Iraq. And so it
has major implications.
Emily Davenport (12:42):
You're investigating the use of stem
cell treatment for strokepatients. So tell us more about
what that means.
Franklin West (12:49):
So we have just completed a major study with Jin
Xie in the chemistry departmentand a number of other faculty
members on campus. And so, whatwe did is we did a study earlier
on where we just transplantedstem cells, and our stroke
animal model. And those stemcells performed phenomenally. So
(13:09):
they were able to turn intoneurons and astrocytes and
oligodendrocytes. And so theseare the critical neural cells in
the brain, right. And so they'reable to replace those cells,
which is important, because manytimes after stroke, you have a
lesion or region where there'sno tissue, so the tissue is
completely absent or it'sdamaged. And so the idea is by
(13:30):
replacing those tissues, you'reultimately going to be able to
restore things like motorfunction, so you're able to
dress yourself in the morning orfeed yourself. And so in
addition to that, we discoveredthat our stem cells produce a
number of neuroprotective andregenerative factors. And so
these are going to be thingslike, brain derived neurotrophic
(13:50):
factor, and they actuallyprevent tissue from dying. And
they also promote naturalregeneration processes. So our
stem cells that we transplantactually communicate with
naturally found stem cells inthe brain, and more than tripled
the number of natural stem cellsin the brain and their response
(14:10):
and migration activity to theinjury site. And in addition to
that, they improved cerebralblood flow. And so we know that
those cells produce somethingcalled veg F, which is involved
in stabilizing blood networks,blood vasculature in the brain,
and also promotesvascularization in the brain.
And so this is a big deal instroke, because the cause of
(14:32):
stroke is the blockage of thatblood vessel. So there's a loss
of perfusion, so blood flow inthat region. So loss of glucose
and oxygen, and so this tissuedies. So if you can actually
reverse that process, it's a bigdeal. And so that was our first
study earlier on. And thisrecent study that we just
published on last month, webuilt upon that initial work,
(14:54):
because one of the things thatwe discovered is we were
transplanting 10 million stemcells into the brain, but many
of them died. And it kind ofmakes sense because we're
transplanting these cells intowhat we call an extremely
cytotoxic environment. So anenvironment that's very toxic,
and it kills a lot of the cellsbecause there's a lot of free
radicals floating around thatdestroy DNA, RNA, lipids and
(15:16):
things.
Sound Effect (15:17):
[chime]
Emily Davenport (15:18):
Free radicals are unstable molecules that
build up in cells and can causedamage to other molecules like
DNA and proteins. This damagemay increase the risk of cancer
or other diseases in the body.
Sound Effect (15:29):
[chime]
Franklin West (15:30):
There's an inflammatory response. And so
what we did with Jin Xie's groupin chemistry is we developed a
nanoparticle that we coulddeliver before we delivered the
stem cells. And thatnanoparticle carried something
called Tanshinone IIA, and it'santi-inflammatory, it's
anti-oxidative, so it quelledthat environment and made it
(15:53):
more accepting for our stemcells. And so we transplanted
our neural stem cells into thebrain. And it improves
survivability and ultimatelyimproved overall recovery of the
animal. So everything fromsmaller tissue damage, decreased
tissue loss, to just improvedneurological scores. And that
last part about improvedneurological scores is probably
(16:13):
the most important piece, atleast clinically speaking,
because we show that it improvedthe ability of animals to stand.
So they didn't need to standwith assistance. And so if you
think of grandparents that havehad stroke, so some of them
aren't going to be able to standor they're going to need a
walker or a cane. When you gotthe treatment, in theory, if
(16:33):
we're translating this topeople, right, they wouldn't
need a walker or a cane. And sowe saw improvements in those
types of functional outcomes.
Ability to feed themselves, sowe look at, you know, can they
feed themselves? Do they needassistance? Same thing in
humans, you know, is that persongoing to need assistance for the
rest of their life to feedthemselves or not? And so we saw
that in our model system andhopefully it translates to
(16:54):
people in a real world way.
Jordan Powers (16:57):
And we actually at the college, put out a story
on the nanoparticle components.
So we'll definitely link thatstory in the show notes for our
listeners. Following up on thatquestion, we know that the RBC
team recently received supportfrom the National Institutes of
Health for your traumatic braininjury research. First off,
congratulations.
Franklin West (17:13):
Thank you.
Jordan Powers (17:14):
It's wonderful that that work is being
supported. Can you talk a littlebit more about what that means
for RBC and how it will affectthe public?
Franklin West (17:21):
Yeah, definitely.
So the proposals that we'relooking at with the National
Institutes of Health focus ontwo areas, the first area is
looking at spontaneous recoveryfrom traumatic brain injury. And
we're focusing on pediatrictraumatic brain injury, which is
kind of a surprise to mostpeople. So about a third of all
traumatic brain injuries occurin children, I think anyone that
(17:43):
has kids has experienced somescares, where perhaps they fell
out of a high chair or off theback of a couch, because kids
are always doing stuff. But mydaughter actually participates
in gymnastics, and she doesthese backflips on a beam. And
every now and again, she kind ofcomes off. And so kids are
typically participating inpotentially dangerous activities
(18:04):
just because they're kids,right. And so that's why we have
so many traumatic brain injurycases in children. And it's
quite insidious, because you canimagine survivors of traumatic
brain injury, at three have tolive with those types of
deficits for the rest of theirlife. Many of them have problems
with learning and memory. Sothey have problems in school,
(18:25):
they have behavior problems, sothings like abnormal fear,
anxiety, stress, almost likePTSD-like symptoms. So post
traumatic stress disorder, andmany of them also have motor
function problems. So they'renever going to be able to be on
the cheerleading squad or playfootball. And so it really
affects these kidssignificantly. And so one of the
(18:47):
things that we're doing is we'relooking at neuroplasticity, and
so about 25% of patients thatsuffer severe or moderate
traumatic brain injury to seemto spontaneously recover. And
it's almost undiscernible ifthey have a traumatic brain
injury. And so the questionbecomes, well, what makes those
patients different, versus theother 75% that are going to be
(19:09):
negatively affected, in somesort of dramatic way. And so
what we're doing, we've teamedup with Qun Zhao, he's in the
physics department. And we'relooking at brain plasticity, and
also cognitive reserves. And sothere's a little bit of science
there for you. But basically,what that means is, we are
looking at how the braincommunicates with itself. So if
(19:31):
you're performing a task, let'ssay 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 actuallyhas to communicate and plan to
pick it up and then tell yourarm to extend, wrap your fingers
around the glass, bring ittowards your mouth, open your
mouth, and then swallow, rightand so this is a highly complex
(19:54):
task that requires coordinationbetween five, six different
centers in the brain, roughlyspeaking. And so how does that
happen? So, in our traumaticbrain injury studies, we're
studying how it happens, orcomparable or more simple tasks,
how that happens before theinjury, and then after the
injury, and so does the brainre-network, and then does it
(20:17):
recruit other parts of the brainto, like, compensate for it. And
we're also looking at differenttypes of traumatic brain injury.
So there's mild, moderate,severe and so, mild traumatic
brain injuries are what footballplayers experience most of the
time on the field when they'rehitting their helmets together.
And so associated with like CTE,so CTE is chronic traumatic
(20:38):
encephalopathy. And sobasically, this occurs when
there's a repeated jarring tothe brain. And so you end up
with micro injuries in thebrain. In fact, they're so
small, that you can't detect CTEusing traditional modality. So
things like magnetic resonanceimaging, so MRI or CT scans,
football players that arediagnosed with CTE can only be
(21:02):
diagnosed post mortem. Soactually, once they remove the
brain from the skull, but it'sbasically from all the impacts
or the forces generated that aredamaging white matter and
leading to microbleeds in thebrain and the like. And then
severe is going to be somethingmore like penetrating traumatic
brain injury. And so the idea isthat with a mild traumatic brain
(21:24):
injury, maybe the brain tissueis there, and it can still do
its job, but it's just not asfast or as efficient. But what
happens to the same area if itno longer exists, which is like
what would happen in a severetraumatic brain injury? So does
it recruit new brain centers?
Does it actually strengthenconnections between other parts
(21:44):
of the brain to kind of pick upthe task? And so those are the
kinds of questions we'readdressing with the first part
of our NIH study. The other partof the study is, we're actually
developing a therapeutic. And sothis is with Aruna Biomedical.
So a company that Steve Stice,my mentor, started up a number
of years ago. And what they'vediscovered is something really
(22:04):
amazing. They're calledextracellular vesicles, or EVs,
in some cases. Our work is donein the past, in stroke,
actually, we have shown that EVslead to reduced lesion size, so
injuries in the brain, they alsolead to decrease intracerebral
hemorrhaging, so bleeding in thebrain, and significant recovery
(22:26):
of motor function and otherfunctional outcomes. And so that
was in stroke. And it works bydecreasing inflammation, a
number of other mechanisms. Andso the thought was, well, this
works so well in stroke, thatit's almost to a point where
it's going into human clinicaltrials. And so that's what Aruna
is doing is taking that to humanclinical trials. So the question
(22:46):
is, well, if it's got the sametherapeutic function and stroke,
let's apply it to traumaticbrain injury. And so that's what
we're doing now in that space.
So we're starting those studiesup pretty soon.
Jordan Powers (22:57):
As colleagues of the College of Agricultural and
Environmental Sciences, can youtell us how agriculture relates
to the work you're doing at RBC?
Franklin West (23:05):
I get asked that question a lot. And what I tell
everyone is that farmers havestrokes as well. And so
ultimately, we're helpingfarmers that do have strokes or
they have children that havetraumatic brain injuries. And so
we may not be helping grow corn,but we are definitely helping
them with their health issueslong term. So. I wish I could
say we're growing soybeans orsomething. It's hard to link
(23:27):
those two.
Jordan Powers (23:29):
Indeed.
Emily Davenport (23:30):
I think maybe too, tying in your work with
pigs might also be a part of theCollege of Ag and Environmental
Sciences?
Franklin West (23:37):
Yeah, so all of our research is actually done in
pig models. And the reason forthat is, anatomically and
physiologically, pigs are morerepresentative of what happens
in humans. And so, let's talkabout stroke for example.
There's been over 700 humanclinical trials based on rodent
(23:59):
data. There are only twoFDA-approved treatments. And so
that's a massive failure totranslate from basic science to
the clinic. So we spent billionsof dollars coming up with
amazing treatments for stroke inrats and mice. So any mouse that
ever has a stroke, we have themfully covered.
Jordan Powers (24:18):
They're set.
Everyone (24:18):
[laughter]
Franklin West (24:19):
They are completely set. It's the people
that are in trouble, though,because in fact, about 85% of
stroke patients still can't getthose two FDA approved
treatments, because of otherlimitations. So we just don't
have a treatment for the vastmajority of stroke patients. And
so there's been a number ofgroups that have tried to
evaluate, "why are we failing totranslate?" Because you can
(24:42):
imagine we've been looking atstroke for over 100 years trying
to come up with treatments. Andone of the big things is we're
studying it in mice and they'rejust not people. And so pigs
have similar brain structure. Sowe call it gyrencephalic, and
that just means that they havegyri, so ridges in the brain,
and the reason that's importantas it affects how the brain
communicates within itself. Italso, when we talk about pig
(25:06):
brains and human brains androdent brains, the human brain
has more white matter thanrodent brains. And so white
matter responds and recoversdifferently from stroke than
gray matter. And so, human'sbrains are more than 60% white
matter, while rodent brains areless than 15% white matter. And
so those are the kinds of thereasons that we're using the pig
(25:27):
model for, because they're justmore comparable. So we think
we're going to get more humanrealistic results, if you will.
Traumatic brain injury is theexact same story, so size of
brain. And also because we'repediatric, we're interested in
brain development and howtraumatic brain injury affects
brain development. And pigbrains actually develop in a way
that's more similar than rodentbrains. So again, more
(25:51):
comparable to humans. And sothings like growth spurts,
myelination of the brain, so thedevelopment of that white
matter. So those things arecritically important. And also,
we're excited about things likenutrition and how that affects
traumatic brain injury. And sowe're able to feed them
different diets, and pigdigestion and nutrition, because
(26:11):
they're omnivores is moresimilar to humans. And so again,
it's more comparable. And onestudy that, this is a side note,
I guess, we're we're reallyexcited about we're doing a
study with Jesse Schank's lab.
He's in the vet school here. Andhe studies alcoholism. And so we
were interested in looking attraumatic brain injury, and how
it increases addictive behavior,and specifically to alcohol. So
(26:35):
a lot of soldiers come back andbecome addicted to alcohol or
opioids. And so the reason we'reinterested in the pig is rodents
innately are not excited aboutalcohol, they don't like the
taste, they don't like thefeeling. However, we discovered
that pigs enjoy drinking just asmuch as you and I do. So.
[laughs]
Jordan Powers (26:56):
I will never look at a pig the same way again.
Everyone (26:58):
[laughter]
Emily Davenport (26:58):
Right?
Franklin West (27:00):
There you go.
There you go. So now we have apig model of alcoholism as well.
Emily Davenport (27:04):
Wow.
Jordan Powers (27:06):
Well, that might be the takeaway. But, if our
listeners could only take awayone thing from this conversation
today, what do you want them toknow about the RBC?
Franklin West (27:14):
So what I would really like them to know is that
the Regenerative BioscienceCenter is committed again to
solving the world's biggestproblems. And we're doing that
from the very basic science allthe way to human clinical
trials. And so we've got greatwork done by researchers like
Rachel Galbraith, and she'sstudying the very molecular
(27:34):
mechanisms of regeneration. Soshe works in an excellent animal
model called planarian. So, it'sa worm, and what she's shown is
you can cut them in half, andone worm now becomes two. And
the question becomes, "well, howdid that other half of the worm
regenerate an entire brain orregenerate other internal
organs?" And so, being able tolearn the basic principles of
(27:58):
tissue regeneration, and thenhopefully be able to apply it
to, you know, soldiers that haveamputated limbs or something of
the like, and so she's lookingat the basic mechanisms. Then we
have other researchers likeJarrod Call, who's looking at
things like volumetric muscleloss. So, going back to soldiers
that have been injured inAfghanistan, a large chunk of
tissue is lost from their calfmuscle, for example. So the
(28:22):
question is, "how do you helpthose soldiers recover their
ability to to walk and run?" Andso that tissue is completely
gone? Well he's looking atmitochondria, and how you're
able to ramp up themitochondria's function. So
they're the powerhouse of thecell, right? And so they produce
the energy, ATP, right? So howdo you ramp up their function so
(28:44):
they can compensate? And so, andthen he's also doing some
exciting things, looking atrehabilitation. I've talked a
lot about some really high endscience, right, stem cell
therapies and hydrogels andthings of that nature. But, I
mean, there's really basicthings out there like, well,
does exercise improve brainrecovery after traumatic brain
(29:05):
injury or muscle loss? And sohe's looking at some of those
things that you can deploy now;they're not 10 years away,
something that you can actuallyapply in the hospital that are
well tolerated today. And sohe's asking basic questions. And
then people like Steve Stice,who is taking his neural stem
cell extracellular vesicles intohuman clinical trials. And so we
(29:26):
have everything from A to Z inour pipeline and I'm really
excited about the work thatwe're doing.
Jordan Powers (29:32):
Dr. West, thank you so much for joining us
today. This was an engaging,enlightening conversation.
Certainly, I think we can divedeeper on so many of these
topics. But in lieu of honoringyour time today, we'll let you
go. But thank you for being withus this afternoon.
Franklin West (29:48):
Thank you so much for inviting me, it was fun.
Emily Davenport (29:52):
Thanks for listening to "Cultivating
Curiosity," a podcast producedby the UGA College of
Agricultural and EnvironmentalSciences. A special thanks to
Mason McClintock for our musicand sound effects. Find more
episodes wherever you get yourpodcasts.
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