Perform cutting-edge research
When Dr. Matlock Jeffries thinks about research, he imagines two arcs. On the first are studies in areas that are already well explored but that require more digging. “Just going deeper,” says the rheumatologist, who investigates arthritis in his lab at OMRF.
This kind of incremental work is necessary but unglamorous, pushing the field forward bit by bit. It is also relatively “safe,” yielding neither breathtaking advances nor punishing failures.
Jeffries confesses to devoting a certain portion of his time to such projects. They provide funding stability and expand the knowledge base. And it’s from this foundation – what is known – that he can leap off onto a second trajectory: the cutting-edge.
To Jeffries, that phrase means moving “away from the light” into “unexplored directions within the research field.” To do this kind of work, he says, “You have to be a risk-taker. Because you don’t know if you’re going to find anything.” It also requires the ability to dust oneself off and move on when an experiment comes up short. Which, he estimates, happens “90% of the time.”
To do the “weird stuff,” Jeffries says, “you have to be comfortable with things not working out.” It can be demoralizing, and the temptation is often strong to retreat to better-understood territory. But for Jeffries, the promise of discovering something truly game- changing drives him to keep probing new realms.
In 2024, he spent a good deal of time pushing the envelope. First, he teamed with scientists at Washington University in St. Louis on a “moonshot” project funded by a newly formed federal agency, the Advanced Research Projects Agency for Health. The agency, known as ARPA-H, has pinpointed a handful of areas of unmet health needs, and osteoarthritis – Jeffries’ specialty and the most common form of the joint disease – is one.
The agency chose the OMRF-Wash U team and four others to chase a lofty goal: begin human clinical trials within five years of a single-injection treatment that promotes tissue regeneration and restores joints. ARPA-H is using a “fail fast” mentality, which will rapidly terminate those projects that don’t show promise early on.
Jeffries, whose role will be to recruit patients and perform the clinical trial once an experimental therapy is developed, hopes his team’s project will survive the cut. “If this works, it could be one of the most dramatic accomplishments of modern biomedical science,” he says. But even if the research doesn’t pan out, he sees big potential upsides. “We’ll rapidly accrue an unprecedented amount of information about osteoarthritis. We’ll identify new molecular targets and develop unique delivery mechanisms.” All of this, he stresses, will accelerate therapeutic development for a condition that is ubiquitous – an estimated 1 in 3 people 65 and older live with it – yet has scarce treatment options.
The lack of therapeutic options for osteoarthritis also drove another groundbreaking study in Jeffries’ lab this past year. Working with laboratory mice, his research team transplanted bacteria, fungi and viruses that lived in the intestinal tracts of a special strain of “super-healing” rodents into normal mice. When the lab attempted to surgically induce osteoarthritis, the condition failed to develop. The findings, published in the Annals of the Rheumatic Diseases, add to a growing body of evidence Jeffries has been assembling to show that microscopic organisms in our gut play a role in causing osteoarthritis.
The next step, he says, will be to determine if specific microbes can offer protection against the disease. “If we can nail down a particular species, or even a few, I can envision a clinical trial testing a probiotic in humans.”
In the meantime, Jeffries will keep searching for paths not taken. In the lab, that is. In his day-to-day life, he says, he’s not much of a daredevil. “I’m more of a tinkerer.”
He recounts a story about when he was 5 or 6 and his mother bought him a flashlight. On the drive home from the store, he was so curious to understand how the device worked that he disassembled it. Completely. “It couldn’t be put back together.”
He chuckles at the memory. Even then, it seems he was beginning to understand that research doesn’t always work out. That if you want to learn something new, you can’t be afraid to break a few eggs. Or at least a new flashlight.
