Posted July 24, 2018
Dr. Dana Gaddy and Dr. Larry Suva
As a married couple, Drs. Larry Suva and Dana Gaddy share a
laid-back, joking rapport that is highlighted by a mutual respect
for one another. But when it comes to their joint research efforts,
the two are serious about solving the health problems that have hit
“closer to the bone.”
Long before Drs. Larry Suva and Dana Gaddy became partners in
life, they were collaborators in the field of musculoskeletal
They met at a small science conference in New Hampshire in 1997,
as Gaddy—an assistant professor at the University of Arkansas for
Medical Sciences (UAMS) who had established her career as a
“card-carrying reproductive endocrinologist”—began focusing her
scholarly attention on menopausal bone loss; Suva, an assistant
professor at Harvard University, was already established as the
“bone cancer guy,” devoting his career to understanding the
skeletal consequences of disease.
“The ‘bone group’ I was in was very dogmatic in their views
because they had been ‘bone people’ for a long time and were not
necessarily receptive to an interloper coming in with a new
perspective, even though that’s what I’d been hired to do,” Gaddy
said. “They wanted me to bring in new ideas, but do it their way.
Because I came from outside of the field, to me, bone was just
another system to learn. I was excited about it.”
Gaddy found that not only was Suva’s group more open to her as a
new researcher in the field, but they were also much more fun.
“We thought she was a post-doc and that we should make her feel
comfortable because the guy we thought was her boss is a nice guy,
but he’s a bit stuffy,” Suva said. “So, a bunch of us tried to
rescue this post-doc, who turns out, was a tenure-track faculty
member. That created a little bit of interaction, as you might
imagine, but that’s what got us, our field, interested in what she
had, because she brought a very unique aspect of reproductive
endocrinology to the bone community.”
The two departed the conference as newfound collaborators whose
work together would extend over the next two decades as they
published on a variety of diseases, including breast cancer, Down
syndrome, and bone anabolic treatments.
“It really stimulated a whole plethora of research,” Suva said.
“Dana was incorporating skeletal ideas into a grant she was
writing. I, and our other colleagues in the U.K., started reading
the grant, helping to edit it, and she ended up getting
After traveling to England for a project at Oxford University,
Gaddy’s career took off and she settled into her faculty position
“My career wasn’t just launched by our interaction—it was a very
fertile environment for me as a new person in the field and there
was huge opportunity to make a contribution; (but) it likely would
not have been so successful if it hadn’t been for Larry and the
folks I met at the Gordon Conference,” she said. “It really helped
to have Larry’s expertise in editing, to get the bone language and
the salesmanship down; that’s really one of his great strengths,
and it continues to be critical to our success.”
In the meantime, in 2000, Suva, who had begun working in the
private sector, began looking to return to academia.
“I had a job offer in Pittsburgh, and then this opportunity in
orthopedics in Arkansas came up,” Suva said. “Dana was in Arkansas,
so I said, ‘Oh, Arkansas? Pittsburgh?’ I chose Arkansas.”
By 2002, Suva was an associate professor in orthopedic surgery
and director of the UAMS’s Center for Orthopedic Research. He ran a
large lab, which was one of the highest-ranked core research
facilities in the state, and enjoyed a continued research
collaboration with Gaddy.
In 2002, they were also married.
Taking Research ‘Personally’
More than a decade into their partnership, Suva and Gaddy were
at another science meeting, this one in Colorado, when they
attended a session on hypophosphatasia, a rare genetic disorder of
alkaline phosphatase, an enzyme mutation characterized by the
abnormal development of bones and teeth caused by defective
mineralization in the body. In humans, it can be quite
“A really good friend of ours who works as one of the world’s
clinician experts in the disease shows a picture of a tooth from a
child with hypophosphatasia; the tooth had come out, roots and
all,” Suva said. “A month before, our granddaughter had been at our
house eating a grape and her tooth came out in the grape. We both
thought, ‘That looks just like Olive’s tooth! Olive has that
Their granddaughter hadn’t been formally diagnosed, so the
couple called the genetics department at Children’s Hospital in
Arkansas and asked a colleague if Olive could be tested.
“We took her in, and there it was—she had hypophosphatasia,”
Suva said. “It all happened from science.”
Because hypophosphatasia is extremely rare and the
musculoskeletal system was their area of expertise, Suva and Gaddy
took matters into their own hands, starting a project that not only
would bring them to the Texas A&M College of Veterinary
Medicine & Biomedical Sciences (CVM), but also would have
serious implications for a disease about which very little is
Creating a Model
Suva and Gaddy
A crucial step in finding a treatment or cure for any disorder,
much less one that has been researched only intermittently, is
creating an animal model to study how the disease progresses.
“Some data exist (on hypophosphatasia) in humans, but it’s
mainly cross-sectional; they may have 20 people with one specific
mutation whom they saw at 10 years old, but they don’t know what
happened when the child was 4,” Suva said. “All they have are
pictures of them at 10 and 15 showing what they look like (with the
Their initial attempts to create a suitable animal model, with
mice, proved unsuccessful, so Suva and Gaddy explored the idea of
using sheep, a validated model for studying the human skeleton.
Because that large-animal model didn’t exist, Suva and Gaddy
turned to the expertise of the CVM for a possible collaboration,
but after visiting Texas A&M, the two decided, instead, to join
the CVM faculty—Suva, as department head of Veterinary Physiology
& Pharmacology (VTPP), and Gaddy, as professor of Veterinary
Integrative Biosciences (VIBS)—so they could create a model without
the obstacles presented by working more than 400 miles away from
Only a year into their work, they are seeing early signs of
success, effectively replicating the disease in sheep by editing
the sheep genome using CRISPR technology and implanting the embryos
The project is exciting for a number of reasons.
“We have built the first real mechanism in which you can
longitudinally study how the muscle develops and then once we know
why it’s weak, identify things we can do that might intervene,”
Suva said. “We’ll see how the disease progresses—what happens when
they’re 2 or 3 years old and how that is impacting them when
they’re 6 or 7.”
Importantly, the next step will involve manufacturing a compound
heterozygote, a sheep that carries exon 5 and exon 10 mutations,
which happen to be the two genetic mutations carried by their
“With this disease, there are more than 300 mutations that have
been reported; most are reported as compound heterozygotes, because
the mother and father don’t know they are carriers and are not
symptomatic,” Gaddy said.
While their research is still in the early stages, their work
already has attracted attention—and funding; one company also has
expressed interest in working to help them understand
hypophosphatasia because of the human implications.
“In order to make a drug for a bone-related disease, the
pharmaceutical industry requires scientists to conduct studies in
rodents and a large animal before humans,” Suva said. “Now, we have
a large-animal genetic model to serve as the platform for that
Being at ‘Home’ with Science
Spending so much time together on such a personal project might
not be possible without Suva and Gaddy’s laid-back, joking rapport,
one also highlighted by a mutual reverence for one another and the
individual strengths they bring to both their working and personal
They work so well together, they say, because, in many ways, they
see themselves as complements.
“It’s a really good combination. I have a really broad view; I
know lots of stuff, but it’s not in great detail,” Suva said. “Dana
is focused in particular areas; so, she can drill down into levels
of information in her brain. She’s got these detailed pockets of
information, like a computer.”
Those aspects of their personalities also carry over into their
“He’s the chef, and I’m happy with that because then I’ll do all
the cleaning. He cooks because that’s his way to relax. For me,
cooking is not relaxing; I do it because it’s necessary,” Gaddy
said. “So, he can relax and cook, and I’ll be happy to relax and
clean. Then I’m happy and he’s happy.”
And while many couples may cringe at the thought of working
together, it’s the science that brings them together.
“I would think 75 percent of the time that we’re together
there’s science involved,” Suva said.
“That’s probably a scary number, but science really intrudes in
everything,” Gaddy said. “It’s not like we end each day talking
science; I can guarantee we’re not that nerdy. But I do think it’s
a lens through which we see life.
“I really feel bad for scientist couples who don’t work
together, because they never see each other when they’re doing
their own thing,” she said. “For me, working together seems much
more rewarding because you can share in success; I feel what we
have is hugely beneficial.”
It may help that their shared research interests allow them to
work toward a common goal, especially as they address issues that
have affected them personally. In addition to their granddaughter’s
hypophosphatasia, both of their mothers died of bone
fractures—Suva’s as the result of bone loss that stemmed from
breast cancer and Gaddy’s as a result of postmenopausal
“The irony of bone researchers having parents die of fractures
and then to have a granddaughter with a rare bone disorder, you
can’t laugh about the irony of that, really,” Suva said. “Talk
“We’ve watched our granddaughter play tee-ball and ice skate,
but she has muscle weakness. She’s 7, and she’s got four teeth
left,” he said. “Only molars,” Gaddy added.
They know the challenge that lies ahead is not only in creating
the phenotype that affects their granddaughter but in utilizing
that information in a much broader way.
“We’re much closer to the disease than we have been in the past
by working in mouse models,” Gaddy said.
“When we started, we didn’t understand anything about teeth. By
the time we get to the next part, we’ll know plenty about teeth. We
know about her muscle weakness; we’ve seen that,” Suva said. “We’re
going to fix it; we’re going to find a way.
“Even if we don’t fix it for her, we’re going to fix it, because
if she ever has a child, that could be a problem,” he said. “We
have always done things to try to improve people’s lives and to
better understand. This got a bit closer to the bone.”
Understanding CRISPR Technology
Trimming, changing, and replacing DNA could revolutionize modern
medicine and prevent common medical conditions.
CRISPR-Cas9 is a gene-modifying tool that targets a specific
area of the genome (an organism’s full set of inheritable
chromosomes), allowing researchers to cut out and insert new
The groundbreaking research, introduced in 2013, has opened the
doors for monumental breakthroughs in medicine by allowing humans
to repair genes responsible for diseases, or, as in the case of
Texas A&M’s College of Veterinary Medicine & Biomedical
Sciences’ (CVM) Drs. Larry Suva and Dana Gaddy, replicate the
genetic mutations that cause hypophosphatasia—an enzyme mutation
characterized by the abnormal development of bones and teeth caused
by defective mineralization in the body—which will allow them to
study the disorder and, hopefully, will lead to its treatment.
CRISPR, pronounced “crisper,” which stands for Clustered
Regularly Interspaced Short Palindromic Repeats, has been
previously researched at the CVM to fight Duchenne muscular
dystrophy, or DMD—a disorder caused by a genetic mutation that
deteriorates muscle as humans age—and in enhancing production
traits in livestock.
W.R. Harvey contributed to this piece (The Battalion, Oct.
For more information about the Texas A&M College of
Veterinary Medicine & Biomedical Sciences, please visit our
website at vetmed.tamu.edu or join us on Facebook, Instagram, and Twitter.
This story originally appeared in the Spring 2018 edition of CVM Today magazine.
Contact Information: Megan Palsa, Executive
Director of Communications, Media & Public Relations, Texas
A&M College of Veterinary Medicine & Biomedical Science; email@example.com;
979-862-4216; 979-421-3121 (cell)
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