Full circle: CAFNR professor is making strides in human health that stem from an observation made 40 years ago

Gary Weisman, Curators’ Distinguished Professor of biochemistry, has spent his career harnessing the power of ATP in its role in immune responses.

Gary Weisman is a Curators’ Distinguished Professor of Biochemistry — a lofty title — and his career has come a long way over the course of four decades. In fact, when he arrived at Mizzou in 1985, the scientific community had largely rejected his research, which is now sparking global curiosity and driving innovation in healthcare.

Weisman’s research career was set in motion when he was a postdoc at Cornell and worked on a team that discovered that adenosine triphosphate, or ATP, a nucleotide component of nucleic acids that provides energy to a cell, exists outside of the cell and is involved in immune responses.

Gary Weisman’s lab team. They are, from left to right, Andy Moran, undergraduate researcher; Luke Woods, lab manager; Kimberly Jasmer, assistant research professor; Gary Weisman, Curators’ Distinguished Professor; Ryan Hutchins, research consultant; Alex Kerns, undergraduate researcher; and Shrikesh (Rick) Sachdev, scientist.

“We were ridiculed by other scientists,” Weisman said of the discovery. “When I came to the University of Missouri, I had a hard time convincing people that this research was real.”

ATP’s role in the immune system was Weisman’s contribution to these discoveries as he was brought onto the team at Cornell to determine why ATP was outside of cells. What he found, and then served as the foundation for the next 40 years of his research at MU, was that the cells were releasing ATP when they were damaged to serve as a signal to the immune system.

“This is a true fire alarm,” Weisman said. “The cell is saying, ‘Hey, fix us. We have damage.’”

Eventually, Weisman and other scientists became curious about a potential connection between this release of ATP and autoimmune disorders. He examined the role of ATP in Sjogren’s disease, an autoimmune disorder characterized by dry mouth and dry eyes.

What he found is changing the landscape of human healthcare.

When cells release ATP in this way, it binds to receptors. Weisman found that when small-animal models were given a drug that disabled those receptors, their Sjogren’s disease symptoms disappeared.

Weisman and his colleagues have applied the same logic to looking at treatment for other health concerns including atherosclerosis and even cancer.

“As I get to this point in my career, I really want to make a difference,” Weisman said, “so, I am pursuing clinical trials and collaborating with other universities.”

Currently, he is working with a team of scientists in the Netherlands and Florida to set up a National Institutes of Health clinical trial treating Sjogren’s disease with ATP receptor blockers in humans.

“This could be very impactful to a lot of people,” Weisman explained. “Sjogren’s can lead to secondary autoimmune diseases like diabetes, and, ultimately, can be fatal.”

Weisman emphasized that his work relies on the talent of his team working in his lab as well, noting that his accomplishments are shared accomplishments with those team members.

“Dr. Weisman is a great advocate for the people in his group, past and present, and has supported every professional endeavor I’ve pursued,” said Kimberly Jasmer, associate research professor working in Weisman’s lab. “Working with him, I’ve found a research niche I’m very passionate about. Gary has provided many opportunities to hone my grant writing skills, and I am now successfully NIH-funded myself. I am grateful for the endless encouragement and advocacy he has provided for me and my career.”  

Weisman is enjoying seeing the fruits of his and his team’s labors fan out to other areas of scientific discovery as well, some of which are happening right here in CAFNR.

“Gary Stacey found the first ATP receptor in plants and is doing really interesting work with ATP in plants,” Weisman said.

Stacey is a Curators’ Distinguished Professor of Plant Science and Technology in CAFNR.

Weisman also sees potential for his research to be applied to animal health issues.

“This research is fun when you’ve finally gotten something to work that you’ve spent so much time figuring out,” he said.