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The power of collaboration

Yale Medicine Magazine, Spring 2024 (Issue 172) Women's Health Special Report
by David Freeman


Multidisciplinary team science seeks to solve biomedicine's big problems.

“One of the things that I like to say about Yale is that from the outside it looks like an Ivy League institution, and from the inside it feels like a small pond,” says Michael Caplan, MD, PhD, C.N.H. Long Professor of Cellular and Molecular Physiology and professor of cell biology.

This, of course, makes Yale School of Medicine (YSM) the perfect setting for the cross-disciplinary tapestry known as team science.

“Everybody knows everybody, and the ethos is that people work together,” says Caplan, a member of several science teams at YSM. “If I call up somebody and say, ‘I’m working on X and you’re working on Y, and let’s see what the cross-product Z looks like’—everybody does that.”

But if an openness to collaboration is one factor in the popularity of team science at YSM, it’s not the only one. The explosive growth of medical knowledge, along with the rise of genomics and sophisticated technologies that require expertise across multiple domains, are other key factors in the expansion of collaborative research at YSM.

As scientific knowledge has accumulated and research tools and technologies have grown more complex, Caplan and other YSM faculty members say that it’s not surprising that individual scientists found it difficult to pursue their research without creating interdisciplinary teams.

“When I started in science in the ’80s, there were a lot of publications where there were two or three authors, the student, and then the principal investigator,” says Peter M. Glazer, MD, PhD, Robert E. Hunter Professor of Therapeutic Radiology and professor of genetics. “Now, that’s very rare, and mostly you see a dozen authors on a typical paper.”

Glazer says that science teams form easily at YSM, in part because of its right-sized pool of researchers. “It’s kind of in a Goldilocks-size range, where it’s not so small that you don’t have enough of a scientific critical mass,” he says, “and it’s not so large that it gets too fragmented and silos develop.”

A leg up in funding

The National Institutes of Health and other major sources of extramural funding have moved in recent years to promote team science by giving preferential treatment to grant proposals from science teams. And for good reason. Studies show that for complex problems requiring a more convergent research approach, teams tend to be more successful than scientists working on their own, according to Stephen M. Fiore, PhD, Pegasus Professor in the Department of Philosophy and director of the Cognitive Sciences Laboratory at the University of Central Florida, and a past president of the International Network for the Science of Team Science (INSciTS).

“You’re trying to bring people together to solve a problem much more rapidly than you would before,” Fiore says, adding that “when we talk about team science, we tend to be describing the more interdisciplinary, more integrative approach to doing science, where you’re creating something new, something that didn’t really exist until that collaboration unfolded.”

Team science at Yale has gotten a major boost from Nancy J. Brown, MD, the Jean and David W. Wallace Dean of YSM and C.N.H. Long Professor of Internal Medicine. She founded the school’s Office of Team Science not long after arriving at Yale in 2020. Its aim is to provide logistical support and act as a nucleus for multidisciplinary teams working to solve some of biomedicine’s big problems. Led by Kathryn “Kakie” Mashburn, director of interdisciplinary research initiatives, the office also provides research teams with preliminary financial support of up to $200,000 through its Program for the Promotion of Interdisciplinary Team Science (POINTS).

Such seed money is often critical to a team’s success, according to Caplan. “You can have all of the creative people that you want and lock them in one room for as long as you want,” he says. “But if they can’t afford to do the experiments or pay the salaries of the people who are going to do the experiments, you’re not going to make as much progress as you’d like.” Adds Mashburn, “The idea is to really encourage people to come together to bring their separate resources, their separate expertise, and to really contribute to a much larger goal to bring infrastructure to the institution.”

Team science in action

The Office of Team Science isn’t the only initiative promoting this form of collaborative research at Yale. The Yale Center for Clinical Investigation (YCCI) maintains a Team Science Program, which not only promotes an academic and clinical culture that supports interdisciplinary research, but also seeks to advance what experts call the “science of team science.” Or, as James McPartland, PhD, Harris Professor in Yale’s Child Study Center and the co-director of the program, explains, it’s about figuring out “how we can understand the functionality of team science … studying processes and developing outcomes to see how team science succeeds at Yale.”

McPartland, who says that he and Mashburn stay in touch to share information and look for synergies between the two programs, also collaborates on studies focusing on autism. As part of the center’s autism research, Flora Vaccarino, MD, Harris Professor in the Child Study Center and director of the center’s program in neurodevelopment and regeneration, recently developed a pair of brain organoids that may help scientists identify different subtypes of autism, which so far remains diagnostically undifferentiated despite the marked heterogeneity of its symptoms, explains McPartland.

Glazer, who is an expert in gene editing, has been collaborating with Caplan on research in mice to discover ways to use these technologies to fight polycystic kidney disease. Another team focusing on polycystic kidney disease, including Caplan along with Stefan Somlo, MD, C.N.H. Long Professor of Medicine (Nephrology) and professor of genetics, and Lloyd Cantley, MD, C.N.H. Long Professor of Medicine (Nephrology) and professor of cellular and molecular physiology, as well as other principal investigators and dozens of Yale researchers, discusses recent findings and proposes new ideas every other week at the Anlyan Center for Medical Research and Education. In addition, the team meets informally and holds video chats. It has been “really productive in terms of developing new insights into disease mechanisms, new animal models, and new therapeutic directions,” says Caplan.

All those meetings and hard work are paying off. Led by Cantley, the polycystic kidney disease team recently obtained a grant of more than $11 million from the Department of Defense. That’s one of the largest grants ever awarded to YSM researchers.

Glazer is also pursuing joint research on cystic fibrosis and other diseases with W. Mark Saltzman, Goizueta Foundation Professor of Biomedical Engineering and professor of cellular and molecular physiology and of chemical engineering at the Yale School of Engineering. Saltzman is an expert in nanoparticle drug delivery. “He has a technology for delivery that needs a cargo, and we had a cargo that needed a delivery vehicle,” Glazer says. “It was a well-made match,” he adds, “and I couldn’t have advanced our work without his delivery expertise.”

The next challenge for the team, which also includes Marie Egan, MD, professor of pediatrics (respiratory) and of cellular and molecular physiology, is to move the experimental gene editing technique from the laboratory to clinical practice, says Saltzman. “We’ve not made that leap yet, but I hope we will” within the next decade.

Other research teams at Yale include those devoted to elucidating the body’s energy metabolism; developing a nasal spray vaccine for COVID-19; and identifying genetic mutations that could be exploited to develop treatments for brain tumors, leukemias, sarcomas, and other malignancies.

But all these successes don’t mean there aren’t occasional challenges. “There are lots of teams that have crashed and burned because the people who participate don’t have that commitment or don’t have those communication skills” needed for success, Caplan says. Emotional intelligence and the ability to listen well are essential, he says. So is being able to keep one’s ego in check, as band members do. “When you are playing in a band,” he explains, “each one of you gets to take the solo at various times. But you can’t be Mick Jagger all the time.”

The good news is that everyone involved in team science at YSM is working toward the same goal. “We want to increase the impact of our science and the benefit that it has for humanity—both in medicine and more generally for the scientific enterprise,” says Anthony Koleske, PhD, Ensign Professor of Molecular Biophysics and Biochemistry and of Neuroscience, and the deputy dean for basic science research at YSM. “We have a world-class faculty that we can build into teams,” he adds, “and they are doing really transformative work.” And this is the epitome of team science.

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