Team Science, Translated

What takes a nutritional supplement into the realm of medical research? The short answer: a study at the Institute of Translational Health Sciences (ITHS), based at the University of Washington.

This study, on an herbal product called resveratrol, is only one among many supported by the ITHS. The institute gives researchers access to mentoring, training, equipment, pilot funding and clinical study resources — all in the service of speeding translational medicine.

Traditionally, translational medicine was thought of as “bench-to-bedside” research, taking a scientific discovery from the investigator’s lab, through a clinical trial in human subjects, and then to a patient’s hospital room or a doctor’s office.

While this picture is not inaccurate, there has been a paradigm shift to a more complex and far-reaching concept of translational medicine. According to UW Medicine’s Mary L. (Nora) Disis, M.D., FACP, and John T. Slattery, Ph.D., vice dean for research and graduate education, it now encompasses a broad range of innovations that improve human health, from drug development to healthcare policy.

And, rather than being conducted by a single, “lone wolf” investigator, innovative translational research depends on collaboration among diverse, multi-disciplinary teams.

“Translational science is team science,” says Disis. “Training people to work as teams throughout the entire translational process is what we have to do to get new [therapeutic] agents into the clinic faster.”

Building the team

Promoting such teamwork is central to the ITHS’s mission.

“At each point in the translational pathway, you need a completely different set of expertise,” says Disis, the director of the ITHS. “If a researcher sees a clinical application for her idea, sometimes she won’t know what to do next. Similarly, if someone is running very advanced clinical trials and notices side effects or an outcome that’s very unusual and needs to find a lab partner, he often doesn’t know where to go.”

Now scientists can go to the ITHS to find collaborators who will help them move scientific discoveries to the clinic as rapidly as possible. A partnership between UW Medicine, Fred Hutchinson Cancer Research Center, Seattle Children’s and other groups, the ITHS was formed in 2007 and is one of 60 Clinical and Translational Science Award (CTSA) sites nationwide — a consortium funded by the National Institutes of Health (NIH).

Disis is proud of the ITHS’s impact. “We’ve developed a membership of almost 2,000 individuals across the region, and have been able to launch resources that weren’t available at the UW before,” she says. Those resources, which include a center for biomedical statistics, a regional research directory, a bio-specimen research repository, access to research networks, eligibility to apply for ITHS pilot funding and other benefits, are available to members at reduced or no cost. Membership is open to anyone interested in translational medicine.

In addition to giving scientific teams the resources they need, the ITHS is working to simplify the Institutional Review Board (IRB) process — a complex series of steps designed to protect the rights of human subjects in clinical trials — in order to facilitate testing novel agents and diagnostics. The ITHS also has piloted the use of the Microsoft Amalga Unified Intelligence System (UIS), a software platform that aggregates research and clinical trial data from across UW Medicine and makes it available to researchers.

Supplements: help or hindrance?

The team science approach that the ITHS fosters is exemplified by its KL2 Multidisciplinary Clinical Research Career Development Program. This NIH-funded program provides up to five years of intensively mentored translational research experience to early-career scientists from all health professions affiliated with the ITHS.

In a recent example, current and past KL2 scholars from a range of disciplines partnered to study resveratrol, a natural substance found in foods such as blueberries and peanuts, which is also promoted as a nutritional supplement. Resveratrol is thought to benefit cardiovascular health, but researchers wanted to see if it interacted — in ways beneficial or otherwise — with other medications a patient might be taking.

Based on experiments performed by Kelsey Hanson, Ph.D., a recent graduate of the Department of Medicinal Chemistry in the UW School of Pharmacy, three KL2 scholars designed and conducted a pilot study to look at the effect of high daily doses of resveratrol on the metabolism of midazolam (a commonly used pre-surgery sedative) in healthy volunteers.

“Our goal was to see if resveratrol actually affects how much midazolam gets into circulation,” explains co-principal investigator Yvonne Lin, Ph.D., a UW assistant professor of pharmaceutics in the School of Pharmacy. Preliminary results suggest that resveratrol has an effect on drug metabolism; these results can help the investigators predict whether resveratrol might interact with other prescription drugs. The study also looked at the accumulation of resveratrol in LDL cholesterol, also known as “bad” cholesterol (when elevated, LDL is a risk factor for cardiovascular disease).

“It’s important that we learn how resveratrol may interact with prescription drugs, as well as its potential therapeutic value in conjunction with other drugs,” says co-principal investigator Ryan Bradley, N.D., MPH, a clinical research assistant professor at Bastyr University, where he directs the newly developed Center for Diabetes & Cardiovascular Wellness.
The power of collaboration

In addition to providing mentoring, the ITHS also provided the team with access to the clinical research center, the assistance of a study coordinator, and pilot funds through a competitive review process. What’s more, the project provided valuable experience for team members as well as data.

“It has been a really fantastic training opportunity for me to have access to UW’s research resources,” says Bradley. “The KL2 program is a significant asset to the School of Medicine, and is helping to create some real experts in multi-disciplinary clinical research.”

“The ITHS fosters a wonderful collaborative research atmosphere,” says Karen E. Foster-Schubert, M.D., M.S., UW assistant professor of medicine in the Division of Metabolism, Endocrinology and Nutrition, and the physician of record on the study. “It gave me formal training in clinical research methodology and helped me take my career to the next step.”

Harnessing science in the region

Currently, Lin and Bradley are conducting a second pilot study — this time collecting data on the interaction of resveratrol and simvastatin (a cholesterol-lowering medication) — in order to support a grant proposal to the NIH. “The ITHS is invaluable in terms of priming investigators to apply for government grants,” Lin says. Ultimately, these studies should shed light on the potential dangers — and benefits — of the interaction between resveratrol and statin drugs.

With this new study, another researcher has been added to the group of collaborators: Pathmaja (Bobbie) Paramsothy, M.D., Fel. ’05, UW assistant professor of medicine in the Division of Cardiology.
“I think that all supplements should undergo the kind of rigor that medications do in terms of clinical studies,” says Paramsothy. “Cardiac patients take so many medications, and it’s critically important for us to study supplements, because they take supplements, too.”

Paramsothy praises the ITHS’s bioethics committee, clinical research nurses and the opportunities it affords for mentoring. She also appreciates being exposed to colleagues from multiple disciplines. “It’s really broadened my perspective,” she says.

That’s a synopsis that pleases Disis; it shows the ITHS is successful bringing people together to speed the pace of medical breakthroughs.

“Our whole goal is to try to harness science in our region and have an impact on health in a very short period of time,” says Disis.