A Team With an Uncommon Bond

immunology team

Kevin Staveley-O’Carroll, MD, PhD, had just accepted the job as surgery chair at the University of Missouri School of Medicine and director of Ellis Fischel Cancer Center, and he needed a house in Columbia.

Fortunately, one had just come on the market in a neighborhood close to campus. Unfortunately, Staveley-O’Carroll was 1,000 miles away.

No problem. His long-time partner in cancer immunotherapy research, Eric Kimchi, MD, was in town on his own house hunt after being named Ellis Fischel’s medical director. Kimchi took a look at the new listing and recommended it.

Staveley-O’Carroll bought it, sight unseen. 

“No pressure there. That couldn’t have gone wrong at all,” Kimchi said with a laugh. “I don’t know if I’d do that with my brother, but with Kevin, with our group, that’s kind of how we work. We know that what the other person is telling us is the truth to the best of our knowledge. That’s an amazing thing.”

It would be tempting to say Staveley-O’Carroll’s five-man cancer-fighting band is like a family. But the team members might be closer than that, as most families disperse for the day and convene at night. This group works together, plays together and even moved to MU as a medical package deal.

Staveley-O’Carroll, Kimchi, Diego Avella, MD, and Jussuf Kaifi, MD, PhD, are physician-scientists. Guangfu Li, PhD, is a
full-time scientist who runs the laboratory.

On the weekends, if you see one, you probably will see them all, along with their significant others. Three of the doctors — Staveley-O’Carroll, Avella and Kaifi — are neighbors, lending credence to the notion that great minds think alike, especially as it pertains to real estate.

“We play tennis, watch sports and have cookouts,” Kaifi said of the group’s activities. “We even go on vacation together.”

The list goes beyond that, including pool parties, ping-pong tournaments, movie nights and jam sessions — Kaifi is a drummer, and Staveley-O’Carroll dabbles on the saxophone.

When Li, formerly a high-ranking officer in the Chinese military, and Staveley-O’Carroll, a wrestling and martial arts enthusiast, meet for a chat at work, impromptu feats of strength can ensue.

“Guangfu and I actually do pull-ups together when we’re talking science,” said Staveley-O’Carroll, who has a pull-up bar in his office right next to the belt he won as the 2009 submission-fighting champion of the nation’s northeast region.

Building a bond

While doing his surgery residency at the Johns Hopkins Hospital in 1992, Staveley-O’Carroll learned about the emerging field of tumor immunology. The idea of treating cancer with immunotherapy was not widely accepted at the time, but it made sense to Staveley-O’Carroll.

Cancer cells are different from normal cells and should be attacked by the body’s immune system as it would other foreign invaders. Somehow, the immune system is tricked into tolerating the cancer cells, which allows tumors to grow without resistance. So if someone could find a way to alert the immune system to the danger of the cancer — to essentially flip its switch from off to on — then the body would start fighting back, halting the tumor’s growth or possibly even destroying it.

Figuring out how to flip that switch became a quest for Staveley-O’Carroll and his team, which began to form a dozen years ago at Penn State.

Kimchi was the first to join, followed soon by immunotherapy enthusiasts from far and wide: Avella from Colombia, Li from China and Kaifi from Germany. They started working with a specific focus on hepatocellular cancer — cancer that starts in the liver.

The only FDA-approved chemotherapy drug for the disease extends life expectancy by just a few months. Surgery is rarely an option, because the cancer usually surfaces in livers too damaged by cirrhosis to recover from the removal of a tumor. 

The first research priority was to develop a mouse model. Avella provided a key breakthrough when he found a way to induce liver cancer in mice with normal immune systems, rather than immunosuppressed mice. That was important because most humans who get liver cancer have normal immune systems. Then Li made the model even more realistic by figuring out how to induce cirrhosis in conjunction with liver cancer.

“I say this very humbly, but this is probably the best animal model for liver cancer in the world right now,” Avella said.

With the perfect platform, the research took off in multiple directions, including immunotherapy testing in conjunction with chemotherapy drugs and radio-frequency ablation. The researchers took off, too, but in the same direction.

Missouri bound

All of the core team except Avella, who was in the midst of a three-year fellowship at the University of Chicago, decided to move together to the University of Missouri two years ago. Avella rejoined the team in September 2017 after finishing his fellowship, saying he never even considered applying anywhere else.

“We were drawn here by the level of engagement at Ellis Fischel, the strong faculty and training programs in the Department of Surgery and the college campus with co-location of the medical school, veterinary school and engineering school,” Staveley-O’Carroll said.

As chair of the Department of Surgery as well as the director of Ellis Fischel, Staveley-O’Carroll’s focus extends far beyond his tight-knit research group.

“My experiences in team-building and our collaborative successes have given me a model that I believe is scalable,” said Staveley-O’Carroll, who wants to develop a world-class department and cancer center. “We have a passion for building and working within effective teams. We have built such a team in tumor-immunology research, and Mizzou is the perfect place to expand this team-building effort in both the department of surgery and the cancer center.”

Mark Wakefield, MD, FACS, the chief of the Division of Urology, was in the process of recruiting a rising star in his field when Staveley-O’Carroll arrived at MU. Wakefield had spent eight years in pursuit of Katie Murray, MD, who was serving a fellowship at Memorial Sloan Kettering
Cancer Center.

“He put together a recruitment package that was thoughtful and effective and set Dr. Murray up for success,” Wakefield said. “Those weren’t tools that I had at that time. Now, I have a good model. So I can see why the people who follow him do so. He creates an environment where there’s the potential for success, and I saw it right away with the help he gave me.”

For Staveley-O’Carroll’s research team, the loyalty to each other and their cause outweighs opportunities for individual advancement.

“Our research, our clinical interest, our social interests are so tied in together.” Kimchi said. “Each one of us has had a chance to go do something on our own, but that would mean breaking up the team and breaking up all the accomplishments we’ve already had.”

The team has the equivalent of three prestigious R01 grants from the National Institutes of Health. The most recent — worth more than $2.7 million — is a multiple-principal-investigator team science award with Staveley-O’Carroll as the lead. It funds a study with a dual purpose. The group will try to determine how a compound developed by bioengineer Mark Kester of the University of Virginia called nanoliposome-loaded C6-ceramide (LipC6) breaks tumor-induced immune tolerance and to develop LipC6-integrated immunotherapy for liver cancer.

“I don’t want to downplay this,” Staveley-O’Carroll said. “It’s a pretty big and interesting discovery, and this is a strategy that will translate seamlessly to the clinic.”

The grant is a testament to the power of a team whose members have helped each other find a home at MU and who have led the University of Missouri to the front lines of cancer research.

“We support each other, we help each other, we benefit from each other,” Li said. “This is a high-performance, high-production team. I really like this environment.”