UT Southwestern researcher James Chen won for his discovery of an enzyme connected to a myriad of medical conditions, including autoimmune disease.
The immune system has a remarkable way of fighting foreign invaders. Antibodies circulating in the blood can latch on to bits of virus, and certain cells can gobble up bacteria. But when wayward DNA gets inside our cells, how does the immune system know?
An answer lies in a discovery made by James Chen, a professor of microbiology at UT Southwestern Medical Center who found in 2012 an enzyme that appears to be the chemical linchpin.
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Now, Chen's discovery has earned him the 2024 Lasker Award in Basic Medical Research and a $250,000 honorarium, the Lasker Foundation announced Thursday. The Laskers, which are among the most prestigious awards in science and medicine, are given annually to "shine a spotlight on fundamental biological discoveries and clinical advances that improve human health, and to draw attention to the importance of public support of science," according to the award's foundation. Chen is among the several Texas-based researchers to win the award in its 79-year history.
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"UTSW is delighted that Dr. Chen's transformative work has been honored by this year's Lasker Basic Medical Research Award as he embodies the decades-long commitment to basic discovery at this institution," said Dr. Daniel K. Podolsky, president of UT Southwestern, in a statement. He added that insights into the enzyme and the biochemical pathway it's involved in "provide a foundation for new approaches to the treatment of cancer and autoimmune diseases as well as vaccine development."
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Chen's discovery was a long time in the making. Born and raised in China, with a doctorate in biochemistry from the University at Buffalo, Chen came to UT Southwestern in 1997. There, he and his colleagues began investigating an immune signaling pathway called nuclear factor kappa B. When the pathway is turned on, the body manufactures chemicals called cytokines, in particular ones called interferons, which are crucial to fighting viral infections. But how interferon production is turned on was a bit of a mystery, Chen said.
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In 2005, he and his colleagues discovered it all hinged upon a protein that senses viral RNA -- a type of DNA -- within cells. This protein was unique in that it dotted the surface of the mitochondria, the cell's energy powerhouse, and so the researchers named it mitochondrial antiviral signaling protein, or MAVS, after Chen's favorite basketball team, the Dallas Mavericks.
This discovery led Chen and his colleagues in 2012 to discover an additional sensor, this time for DNA. It was far more curious to them because it was an enzyme, a class of proteins that act as biological catalysts to speed up chemical reactions.
"Back then, it was quite a surprise," Chen said. "We know that there must be a sensor that detects DNA, so when we set out to do this, we thought it would be just a protein binding to DNA somehow. We didn't expect it to be an enzyme."
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When the enzyme, called cyclic GMP-AMP synthase (cGAS), detects any type of DNA in the cell's soupy interior -- also known as the cytoplasm -- it produces a molecule that activates the innate immune system, the body's first line of defense to foreign threats.
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In the years since the enzyme's discovery, Chen said, there's been a wave of research into its implications not just for fending off infection but also for a myriad of medical conditions rooted in the immune system.
"There are many labs and companies that are working on targeting this pathway for the treatment of human diseases that range from cancer immunotherapy to autoimmune diseases and, of course, infectious diseases as well," he said. "There are also efforts to dampen this pathway, to inhibit [it] in autoimmune diseases because often the case is that this pathway is hyperactivated and you want to calm it down."
The significance of winning the Lasker isn't lost on Chen. More than 80 previous winners have also won a Nobel Prize, including 43 in the last three decades. At UT Southwestern, three professors have won both the Lasker and the Nobel: Dr. Michael Brown and Dr. Joseph Goldstein, who jointly won the 1985 Lasker in Basic Medical Research and the Nobel in Physiology or Medicine in the same year, and Alfred Gilman, who won the 1989 Lasker in Basic Medical Research and the Nobel in Physiology or Medicine in 1994.
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For the most part, Chen doesn't think about whether a Nobel will one day grace his mantelpiece.
"What is most exciting is making discoveries that have never been found in humans or any sort of multicellular organism," he said. "We just focus on our work."
Miriam Fauzia is a science reporting fellow at The Dallas Morning News. Her fellowship is supported by the University of Texas at Dallas. The News makes all editorial decisions.