Jan. 17, 2017
by Susan Keown
Some people jump out of airplanes or climb sheer rock cliffs without a rope. Dr. Anthony Rongvaux does neither.
Instead, he finds his thrills in the lab, where he is searching for the next big questions in immunology hiding in plain sight, just waiting for him to notice them.
“That’s the kind of big challenge we’re looking for, that we’re not trying to avoid,” said Rongvaux. Just like some people compulsively look for risks in the realm of airplanes and mountains, he said, “it’s probably the same for us scientists ― it’s addictive.”
Rongvaux’s specialty is the innate immune system, the first responder of the body’s defense system. (When you get a cut, for example, the innate immune response is what makes the area turn red and begin to swell just seconds after the injury.) He wants to know: How does the innate immune system recognize abnormal cells like cancer?
“There’s this kind of arms race between the immune system that tries to recognize the tumor as something to get rid of and a ‘successful’ tumor ― a tumor that’s going to develop strategies to escape from this detection by the innate immune system,” said Rongvaux, who is a faculty member in the Immunology Program at Fred Hutchinson Cancer Research Center. “If we can understand this language between the two, we can find ways to interfere with it and potentially develop new therapies.”
Rongvaux came to Fred Hutch from Yale University in 2016, drawn by the Hutch’s commitment to basic research and to translating those fundamental discoveries in the lab into clinical breakthroughs that help patients.
From a youth spent birdwatching and fiddling with electronics in his native Belgium, to the college immunology class that sparked his current research interests, science has always come naturally to Rongvaux. It never occurred to him to do anything else.
The best part of being a scientist, he says, is that you can discover the unexpected, things that no one knew before or even suspected. How to do this? The simplicity of the answer to this question belies how challenging it is to do in practice: Open your eyes.
Back at Yale, Rongvaux was studying a gene that regulates cell death, trying to figure out how it affected the blood-forming cells in the bone marrow. He observed something that made him scratch his head: Strangely, the dying cells were activating genes involved in innate immunity. He decided to dive into the rabbit hole of this mystery and follow wherever it led. He discovered, to his surprise, that the responsibility for this phenomenon lay with the stressed cells’ energy-producing factories, called mitochondria, which had the power to trigger ― and to silence ― their host cells’ production of inflammatory signals, without the involvement of any immune cells.
“No one can predict something like that,” said Rongvaux. “That was a very new mechanism, completely unsuspected.” He is now trying to figure out when this response occurs and its relevance in health and disease.
An important tool in his studies is a powerful laboratory model of the human immune system he and colleagues developed at Yale, which allows him to manipulate particular aspects of the immune response and study its activities in depth. With its close fidelity to human immunity and the ability to recapitulate humankind’s diverse array of immune systems, the model is a great tool for early tests of new immune-modulating therapies, like vaccines.
Rongvaux is still in the early phase of his career. But he hopes that someday in the future he can look back on his lifetime of work and say that he’s contributed a critical piece of the puzzle that is our knowledge of the immune system, a piece that has made possible lifesaving advances for patients.
“That is something I don’t think a single researcher can do on his own,” Rongvaux said. “We’re contributing to that collectively.”