Understanding Genetic Instability May Be Key to Eliminating and Preventing Cancer
Richard Adeyemi, Molecular Biologist
Dr. Richard Adeyemi has spent his entire life studying how to put broken things back together. Nowadays this means furthering our understanding of how cells maintain the integrity of their DNA and repair genetic damage that could lead to cell death or worse, cancer.
To the consternation of his parents, this proclivity arose early in Adeyemi’s life.
“Every toy that I had, I would destroy it and try to put it back together again to see how it worked or what made it move,” he said.
Adeyemi’s curiosity soon extended to everything around him. Luckily for him, his mother was a biology teacher.
“I was fortunate I could just ask her everything, and she would answer... at least until she’d eventually get too exasperated,” he joked.
It shouldn’t be much of a surprise that as a high schooler, biology was Adeyemi’s favorite subject.
“I just fell in love with it,” he said. “As a result, my teacher pushed me to go into the biological sciences as a career, so I decided to go to university.”
In Adeyemi’s home country of Nigeria, the expectation is that you choose a career specialization early on. This led him to focus on premed courses during the latter stages of high school and later attend a university program in veterinary medicine. His vet training included a research requirement, which steered the course of his life towards science. For his research project, he investigated bird viruses and how chickens’ immune systems respond to those viruses. It was through this project that he became fascinated with understanding the world at a molecular level and how biological processes working at this level can affect health.
“While I started my vet training focusing on the whole animal, I then got interested in viruses and then how the virus interacts with cells. At each level, everything just kept getting smaller and smaller,” he said.
But as his interests grew smaller, his ambitions grew bigger. Almost as soon as Adeyemi received a doctorate in veterinary medicine, he decided to get a PhD in molecular virology.
This interest brought him to the United States, where he studied a type of virus called a parvovirus that uses an ingenious, yet insidious, method of tricking a cell into replicating the invading microbe. The viral DNA disguises the fact that it doesn’t belong by convincing the cell that it is merely innocently damaged cellular DNA. The cell then quickly gets to work trying to “repair” the DNA, and in the process helps the virus spread.
Adeyemi found that experimentally turning off a cell’s ability to repair its DNA also prevented the virus from replicating. Adeyemi’s discoveries made crucial breakthroughs into the understanding of how parvoviruses replicate, but also led him to appreciate just how much more there was to understand about the mechanisms of DNA repair.
“So that got me from where I was interested in understanding the viral response itself to how our own cell’s DNA is repaired,” he said.
Since then, Adeyemi has been focused on understanding how our cells maintain the integrity of their DNA. Our DNA can become damaged in numerous ways, including normal cellular process like transcribing information from genes into RNA, and external events like radiation exposure and viral infection. Damaged DNA, if not repaired, can lead to unregulated cell replication resulting in cancer.
“One hallmark of cancers is that they have increased genetic instability, which is a way we describe a cell’s propensity to accumulate genetic mutations,” Adeyemi said. “This instability can cause a cell to override the brakes and continue to divide uncontrolled.”
While these genetic instabilities can underlie the development of cancer, they may also be the source of better treatments since these mutations often make cancer cells suddenly dependent on backup pathways for survival.
“I’m working to find the Achilles heel of certain cancers that have genomic instabilities to discover how we can exploit their weaknesses to eliminate the cancer cells,” Adeyemi said.
Ultimately, a stronger understanding of how genomic instability leads to cancer could be the key to preventing cancer from developing in the first place. A deeper knowledge of how healthy cells repair their DNA will help us determine the risk factors that may lead to diminished DNA repair and possibly reveal how to restore function to unhealthy cells.
“When some people are born, they're predisposed to certain cancers. By sequencing their DNA, we could find a genetic predisposition for certain cancers and then introduce either a direct genetic fix or design targeted RNA for the cancer cells to stop them from spreading,” he said.
Though the promise of Adeyemi’s research is monumental, he acknowledges how much effort lies ahead.
"I really love discovery. I love finding things out that haven’t been found before."
“There are many ways this knowledge will help down the road, but it's still really early at the moment and still needs a lot of work before developing these novel therapies,” he said.
Despite this, Adeyemi is determined, because the long-term benefits are so substantial. He envisions a future where, having mapped and characterized the molecular mechanisms of several tumor suppressor genes, “we can catalog the set of genes that are specific for a particular patient’s cancer and then they can simply go to the pharmacy and pick up a drug that targets and treats their cancer.”
He believes that Fred Hutch’s collaborative atmosphere will help bring about this future as it breaks down the barriers to doing the best research at a pace that will have meaningful impacts both in the near and long term.
“Fred Hutch is just the whole package. The people here are really interested in doing great science,” he said. “Other labs are really collaborators, it’s an environment of collaborative spirit.”
Despite the potential impact of his research, Adeyemi said his day-to-day motivation is a bit simpler. “On a personal level, I really love discovery,” he said. “I love finding things out that haven’t been found before.”
More than just making discoveries, he said, it’s “being able to share those discoveries with people that makes you continually fall in love with science.”
— By Matthew Ross, July 11, 2023
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