It's Safe to Say--Impact Begins at Discovery
Posted July 03, 2017
Dr. Stephen Safe
Discovery and the unexpected—these are recurring themes in the
research career of Dr. Stephen Safe, a distinguished professor at
the College of Veterinary Medicine & Biomedical Sciences (CVM).
Trained as a chemist, Safe eventually found himself studying
toxicology and examining the biochemical mechanisms of cancer with
the hopes of developing effective drug treatments.
Safe looks at receptors, a molecular lock to which chemical
signals are the keys. When these chemical signals bind to the
receptor, or turn the metaphorical key, it leads to a Rube
Goldberg–like process, where one action affects another and then
another, ultimately powering various biological processes.
“Receptors are needed for life,” Safe said. “They are sensing
molecules. They sense light. For example, you need sunlight to
produce Vitamin D. What does Vitamin D do? It would do nothing if
there wasn’t a Vitamin D receptor.”
And, it all started with a single receptor—the aryl hydrocarbon,
or AH, receptor. Known to play a role in a chemical’s toxicity in
the body, the AH receptor was not known for its health benefits.
However, research trends led Safe and his colleagues to suspect
that this receptor’s function was far from black and white. There
were, in fact, health benefits yet to be uncovered.
“I started off working on toxic compounds that bound to the AH
receptor. It was always thought to be a receptor that was important
for driving toxicity of various chemicals that bound to it,” Safe
said. “Many people have discovered in the last 20 years that this
receptor plays a huge role in all sorts of things, including the
health of your gut, the health of your skin, and autoimmune
diseases. We’ve been looking at ligands—or compounds that bind this
receptor—that aren’t toxic. We’re using them for treating cancers,
and investigating the heath benefits of the receptors in gut
Excited by the possible health benefits associated with the AH
receptor, Safe began looking for practical solutions to ailments
such as pancreatic cancer. Through partnerships with pharmaceutical
companies, Safe is working toward developing effective drug
treatments that would specifically focus on receptors like the AH
and NR4A1 receptors to promote pathways that prevent cancer growth.
“We’ve got a new group of drugs that look like they’re really going
to knock your socks off,” Safe said.
Dr. Safe with his research team in the laboratory
Safe’s interest in the AH receptor has stimulated an interest in
other receptors, such as NR4A1, which Safe and his colleagues are
investigating for the treatment of multiple cancers including
rhabdomyosarcoma—a devastating children’s cancer. “We think the AH
and NR4A1 receptors are really important in cancer, and we’ve been
developing drugs that target them through different pathways,” he
Developing these drugs can be a balancing act, looking for the
appropriate dose to ensure effectiveness. “We’re trying to develop
drugs that we can give at a much lower concentration to hopefully
be below the toxic threshold. We think that they have relatively
low toxicity and expect that the side effects will be minimal. In
addition, they’re also useful for combination therapies.”
Safe’s fascination with the AH receptor has caused his research to
take an unexpected turn. In collaboration with other researchers at
Texas A&M, he is focusing on the effects of microbial and
food-derived AH-receptor compounds on gut health. For example,
eating cruciferous vegetables, such as cabbage, could provide
similar effects as the compounds acting on the AH receptor. “Maybe
plants that produce a lot of AH receptor compounds, like
cruciferous vegetables, which are known to be health-protective,
could be combined with what the microbiota produces. The two in
combination could be dynamite,” he said.
The twists and turns of Safe’s research has led to continuous
learning and a deep curiosity. “The good thing for me is I started
off as a chemist and all we do in my lab is oncology and molecular
biology. So, I’m learning all the time,” he said. Beyond the AH
receptor discovery, Safe continues to search for much needed
practical, life-saving therapies.
For more information about the Texas A&M College of
Veterinary Medicine & Biomedical Sciences, please visit our
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Contact Information: Megan Palsa, Executive Director of
Communications, Media & Public Relations, Texas A&M College
of Veterinary Medicine & Biomedical Science; firstname.lastname@example.org
; 979-862-4216; 979-421-3121 (cell)
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