In 2007, Marcus Bosenberg was ensconced at the leafy, bucolic University of Vermont campus with what some academic physician-scientists might consider a dream career. He was a Harvard University–educated, National Institutes of Health–funded scientist with his own lab and an active clinical practice in dermatology. A sought-after speaker who had developed a mouse model of melanoma, Bosenberg was just weeks from obtaining tenure. He had it all. And then he gave it all up.
"It seems to me that the only way to do this, if we are going to be able to advance therapies, is to collaborate with our scientific colleagues and find targets and better treatments." --Mario Sznol, oncologist and co-director of the Yale School of Medicine melanoma program
"I was never really thinking I would ever move," he says. "I really enjoyed the life I had there."
The decision to move came after giving an invited talk to the Yale School of Medicine melanoma research group, a National Cancer Institute (NCI)–funded Specialized Program of Research Excellence (SPORE) in interdisciplinary translational research. During his visit, he met a team that clearly enjoys working together, a trait not on display in some of his experiences at other academic institutions. Bosenberg was so impressed that he left Vermont to accept an untenured position in the Yale Department of Dermatology so he could work with this melanoma research team.
"You look at some institutions and there's a great group of potential investigators that could work together but don't, unless the grant cycle comes around again," he says. "There's not enough time in life to be fighting. Here was a group that would be enjoyable to work with while at the same time hopefully discovering very important things for patients."
Three years later, Bosenberg is involved in projects that would have been out of reach at Vermont, working as part of an 80-member team led by veteran melanoma researcher Ruth Halaban, a molecular biologist who studies genes that control the malignant transformation of melanocytes.
It's been 5 years since the melanoma group formed, and members say they feel they have assembled a team that is prepared to quickly translate laboratory findings to help patients in the clinic. Science Careers spoke with Halaban and several other team members to find out what components have been integral to their success, both in terms of research results and in functioning as a team.
Breaking down barriers
Halaban has been attending weekly melanoma meetings in the medical school since 1973. But until the last few years, she says, "nobody ever asked me, 'What do you think?' because they knew I could not give them any answers."
More recently, though, Halaban has seen a transformation in attitudes toward multidisciplinary team science. The game changer was the discovery of specific gene mutations in melanoma, which has subsequently led to the identification of targeted inhibitors of the notoriously difficult-to-treat cancer. Now, Halaban says clinicians and laboratory scientists are energized to work together to ensure that molecular markers for melanoma turn into promising avenues for new therapies.
Laser focus on the research goal
The Yale group proceeds from the premise that understanding the basic biology of the melanocyte will lead to tailored treatment that addresses pathways of malignant transformation. Stemming from that premise, investigators are working on several therapeutic avenues. For instance, the group used a genome-wide epigenetic screen to identify novel methylation markers for melanoma and is now using patient samples to assess the prognostic value of these markers.
For Michael Krauthammer, the team's bioinformatics guru, the appeal of joining the team sprang from the sense that this team was prepared to make big strides. "The most appealing factor about this group was that it was on the brink of translation," Krauthammer says. "It was clear the main goal was to bring new therapeutics into the field of skin cancer."
Mario Sznol, an oncologist and co-director of the melanoma program, says he couldn't face his patients in clinic unless he knew he was leaving no stone unturned in the search for new treatment. "It seems to me that the only way to do this, if we are going to be able to advance therapies, is to collaborate with our scientific colleagues and find targets and better treatments."
The flipside of maintaining this focus is that if something isn't working, it is quickly identified and the project halted. Sznol put the brakes on one of his projects when it didn't meet its goal of leading to a clinical trial in 2010. To ensure equity in decision-making, the group has both an internal advisory group that meets monthly and an external advisory board that meets annually to review research progress.
Putting infrastructure in place
From the beginning, there was a commitment to putting in place the long-term infrastructure needed to do complex studies that use patient samples combined with genetic, epigenetic, and physiological measures that produce large, interrelated data sets, Halaban says. One of the first decisions was to invest in tissue banking to ensure that biopsy samples collected from patients are stored properly so that they're useful for years and even decades to come. That investment included hiring a full-time coordinator and training surgeons and technicians to collect and process samples within minutes of excision. "It takes very dedicated surgeons, because without the surgeons on board we are getting nothing," Halaban says.
That investment paid off, in part, Sznol says, because the group put in place standard operating procedures that have turned the tissue-collection system into a "well-oiled machine." Surgeons can rely on dedicated on-call technicians to retrieve the collected tissue within minutes of excision. The tissue bank uses caTISSUE, an NCI-sponsored specimen tracking system connected to a data-sharing network that's designed to facilitate collaboration among melanoma researchers beyond Yale. Data from the tissue bank contributed, for example, to a new prognostic indicator for melanoma recurrence, developed by Yale investigator David Rimm and his colleagues.
Group members cited physical proximity -- they are all within a 5-minute walk of each other on the Yale campus -- as a reason their group works so well together. Not all team science projects have that luxury, and it helps, Bosenberg says.
Weekly meetings at which faculty members, medical fellows, and/or students present their research provide platforms for people to discuss their work in a supportive setting, Halaban says. It also informs team members what everyone is working on to avoid competing within the institution. And group leaders participate in a monthly conference call with the other three NCI-sponsored skin cancer SPOREs to exchange ideas.
One of the oft-cited barriers to effective team science endeavors is difficulty communicating across the language barriers separating disciplines. The Yale group is not immune to such problems. For example, the group generates large volumes of genomic data, and all of it goes through Krauthammer's bioinformatics core. "Sometimes there's a gap in understanding what's needed to get data into viewable format," Krauthammer says, and "it sometimes takes longer than people think it should." The solution to these problems is usually pretty simple, he says: Make an effort to learn something about your collaborator's abilities and limitations and adjust your expectations.
Leaving ego at the door
"[Our group] is as close as you can get to a productive environment that is not hindered by politics," Krauthammer says. In 12 years of hospital service and laboratory research, he has seen politics in action. "That can hinder a lot of creativity," he says. In contrast, within the melanoma group, Krauthammer says, the relaxed, cooperative atmosphere allows him to learn from his colleagues and stretch himself scientifically.
Halaban says an open environment promotes more discussion across fields, which is very much preferable to having people keep quiet because they're afraid of exposing ignorance in areas outside their specialties. "My oncologists are constantly coming to me and asking, "What else do you know about the molecular signature of these patients?' " Halaban says. Bosenberg adds that there are at least 10 projects in which he participates by sharing reagents, crossing his mice with other investigator's mice in pilot projects, or sharing his experiences in group meetings -- all aimed at contributing to other researchers' endeavors.
"The clearest evidence of how things have changed is that I am a co-PI [principal investigator] on three or four grants now in areas I never would have imagined at Vermont," Bosenberg says. An example: "We are trying to find combinations of drugs that work in particular subsets of melanoma, which is something I never would have done, would never even have thought of doing, before I came to Yale."
Even though the group has one major goal -- to find better treatments for melanoma -- there are many avenues for exploration that the 12 current principal investigators have their own niche within the larger group, and -- Krauthammer says -- there is no internecine competition for turf.
A supportive environment for trainees
Just as Bosenberg was attracted to the melanoma group for its members' enthusiasm and success, the campus's best students are drawn to the group as well, Krauthammer says: "It's very attractive to them to be in a translational enterprise." The bioinformatics students and postdocs "feel very strongly that it's kind of cool to be at the verge of clinical discovery."
Junior investigators within the group are annually invited to apply for smaller, $50,000 seed grants funded through the Yale SPORE to develop new ideas. "It's a very protective environment because young scientists or young fellows can do some work without having to compete nationally for grants," Halaban says.
Encouraging contributions from everyone -- yes, everyone
"If you talk about translation, it really means that for all of those involved, there has to be data transparency … because the driving ideas could come from any side," Krauthammer says. "Patients might have a good idea what to look at. You can't preclude anyone from contributing to the mission. That's, for me, part of the translational enterprise."
Krauthammer's research combines disparate sources of data and mines existing data in new ways. Through his interaction with the melanoma group, he has contributed to NCI's massive caBIG project, which is attempting to create accessible virtual portals for cancer data. Krauthammer says he is exploring the caBIG tool caIntegrator, which brings together searchable clinical, microarray, genomic, and medical imaging data so that investigators not versed in bioinformatics can explore data on their own.
The leadership of the Yale group encourages innovation from everyone involved, he says. "They are very encouraging for anyone to step up and produce," Krauthammer says. "I feel that I am coshaping new branches and directions that are being spun off right now, and that's quite satisfying, actually."
Karyn Hede is a freelance writer in Chapel Hill, North Carolina.