funding initiative speeds innovation
to improve health

Each dot denotes a faculty member of the ICTS, and each connecting line represents a collaboration between faculty in submitting an NIH grant application. ICTS began in 2007, above left, and by 2010, above right, there had already been a dramatic increase in the number of collaborations and the density of interconnections among research groups.

DOUGLAS LUKE AND BOBBI CAROTHERS, CENTER FOR PUBLIC HEALTH SYSTEMS SCIENCE, WASHINGTON UNIVERSITY

icts.wustl.edu

BY JULIA EVANGELOU STRAIT

Whether providing pilot funding to gather initial data or final funding for projects heading toward publication, grants awarded by Washington University’s Institute of Clinical and Translational Sciences (ICTS) are ultimately aimed at one goal — supporting medical research that has the highest likelihood of benefiting patients quickly.

“Facilitating new research collaborations across traditional disciplinary boundaries is a major goal of the ICTS,” says director Bradley A. Evanoff, MD, MPH, assistant dean for clinical and translational research. “By doing so, new discoveries can more rapidly be translated into prevention, diagnosis and treatment.”

Washington University’s ICTS is one of 60 such programs across the country. It is funded through institutional resources and through a five-year, $50 million Clinical and Translational Science Award (CTSA) given by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH). In its first six years, the ICTS has awarded $6.9 million to 70 projects and, in June 2012, its CTSA grant was renewed for an additional five years.

The ICTS pursues its mission by supporting new research infrastructure, funding translational research, training young faculty, and facilitating collaborations across disciplines. Its research support cores provide expert consultation and resources in tissue banking, imaging, biostatistics, biomedical informatics, research ethics, experimental design, conducting clinical trials, genomic analysis, regulatory support and community-engaged research. And that’s just the short list.

Through all of these activities, the ICTS is a pillar of Washington University’s BioMed 21 initiative, an effort dedicated to translating basic science discoveries into solutions for the world’s biggest health problems.

“Our researchers work across departmental and divisional specialty lines to a greater extent than ever before,” says Evanoff. “We can’t claim credit for all of that, but we’ve been one of the forces helping people make connections.”

Kelle H. Moley, MD

better
infant care

mothers' tissue samples illuminate children's diseases

One example of the school’s connectivity is embodied in the Women and Infants’ Health Specimen Consortium, a program led by Kelle H. Moley, MD, co-director of the ICTS and the James P. Crane Professor of Obstetrics and Gynecology.

The consortium was founded in 2007 by Moley and Ann M. Gronowski, PhD, associate professor of pathology and immunology, with the help of an ICTS pilot grant. Investigators from a wide range of specialties are involved, including pediatrics, microbiology, obstetrics and gynecology, pathology, internal medicine and developmental biology.

The purpose of the consortium is to gather tissue samples from women before and during pregnancy, after delivery, and from the newborn. The tissues collected include cord blood, maternal blood, newborn blood, placenta samples and amniotic fluid.

The samples, which are linked to clinical reports of the health of the mother and her baby, are available to investigators interested in a wide array of issues important to women and newborns, from repeated pregnancy loss, pre-term delivery and pre-eclampsia to endometriosis and sexually transmitted diseases. It also may provide insights into the origins of childhood diseases and the communication that goes on between the mother and fetus in utero.

“This resource allows investigators to have access to unique samples that they would not normally be able to get on their own,” Moley says. “We have about 3,000 patients participating in the program and more than 200 patients that we have followed throughout the process — pre-pregnancy, pregnancy, and after delivery.”

Moley co-directs the ICTS in part because her own research sits at the interface of basic research in the laboratory and clinical research that can help patients. An expert in reproductive health, her primary focus has been endocrine disorders in women, such as those related to obesity, diabetes and polycystic ovarian syndrome, and their effects on fertility.

“My work with the ICTS has forced me to think more about how my own research can be applied to improve health care,” Moley says. “My job is also to ask other basic scientists to think about ways that their research can affect human health directly and to encourage them to become involved with the ICTS.”

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Randall S. Sterkel, MD, and Jane M. Garbutt, MBChB

into the
community

aiming for consensus in private practice clinical care

Taking medical research into the community and helping physicians in private practice is another goal of the ICTS. Jane M. Garbutt, MBChB, research associate professor of medicine and pediatrics, has been a pioneer in this effort.

Many times care for common conditions, such as sinus infections or pinkeye, differs greatly from one doctor to the next. To help determine the best solutions for these typical ailments, Garbutt established the ICTS-supported Washington University Pediatric and Adolescent Ambulatory Research Consortium (WUPAARC), a network of local pediatricians in private practice who are interested in improving clinical care.

“We try to make our research relevant and useful to primary care doctors,” Garbutt says. “If you just conduct research studies in academic institutions, the patients may not be representative of the patients going to see their regular doctors. If we recruit patients through primary care practices, we get more diversity in the patient mix.

“And the results will be relevant to other doctors with similar practices. The physician can look at these studies and say, ‘These patients look similar to mine, so the results should apply to them, therefore I will change my practice.’”

Currently, 66 pediatricians and five nurse practitioners from 35 medical practices in the St. Louis area participate in WUPAARC. The pediatricians themselves suggest the questions to be studied by the consortium.

One ongoing trial is looking at whether peer coaching delivered by telephone for mothers of children with asthma will help better control the disease. Asthma coaches help the mother develop a collaborative relationship with the child’s doctor and provide education and support to encourage effective use of asthma medications.

Garbutt’s own research is focused on improving the quality of care in the ambulatory setting. She shares her expertise in these community-based research methods and logistics with other investigators at the university so that they might also begin studying ways to improve health care in the wider community setting, where so many people receive their medical care.

“The success of any research network is dependent on personal relationships,” Garbutt says. “We have to build a network that transcends one study. We have to build the relationships and structure needed for research and then nurture it.”

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Matthew J. Ellis, MD, PhD

advanced
resources

modeling deadly cancers may lead to new treatments

Along with its commitment to community-based research, the ICTS also supports work that is done in animal models of disease with a clear pathway to improving human health. One example is a core resource devoted to studying human breast cancer tumors in living organisms.

The Human and Mouse Linked Evaluation of Tumors (HAMLET) Core is led by breast cancer expert Matthew J. Ellis, MD, PhD, director of Breast Oncology at Washington University and co-leader of the Breast Cancer Research Program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

With this resource, researchers can study living tumor cells in a preclinical model. The growing tumors are genetically similar or identical to the original tumor and they provide excellent test subjects for developing new imaging techniques and performing early studies of new drugs and therapeutics.

A major success stemming from this relatively new core resource culminated in a paper published in Nature in 2010. The study looked at four DNA samples from a single patient with basal-like breast cancer, an aggressive form of the disease more common in younger women and African-American women. The four samples came from the patient’s primary tumor, peripheral blood, a brain metastasis, and a primary tumor sample grown by the HAMLET Core.

The HAMLET Core tumor differed in important ways from the primary tumor and had remarkable similarities to the tumor that had spread to the patient’s brain. Such evidence sheds light on the mystery of how cancer metastasizes and suggests that a small number of cells in the main tumor can give rise to secondary tumors that spread throughout the body.

“Basically what’s growing in the mouse is another metastasis — the most malignant version of the tumor,” Ellis says. “So this resource is helping us model the most deadly types of breast cancer, and that’s what we need to focus on. We want to make these models freely available and collaborate widely to solve an extremely complicated biological problem.”

Since the Nature study, an additional 16 models have been deeply sequenced and those findings were released at the recent American Association of Cancer Research meeting. The findings show that human-in-mouse copies of breast cancer are very clearly excellent genomic and functional mimics of the disease. The approach is so promising that the HAMLET Core plans to expand and include additional tumor types, likely starting with pancreatic cancer.

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Robert C. McKinstry, MD PhD, and Pamela K. Woodard, MD

bright
outlook

high-tech imaging bridges research and application

Another important goal of the ICTS is to help more investigators take advantage of the university’s existing technology. A prime example is the ICTS Human Imaging Unit, housed in the Center for Clinical Imaging Research (CCIR) in the Mallinckrodt Institute of Radiology.

The ICTS Human Imaging Unit is led by Robert C. McKinstry, MD, PhD, professor of radiology and of pediatrics, and provides access to five state-of-the-art imaging scanners. Pamela K. Woodard, MD, professor of radiology and of biomedical engineering, leads the CCIR.

“We want to make sure researchers know that this resource is available to them and that funding opportunities exist to support pilot projects that can then be used to apply for larger grants,” Woodard says. “Our equipment is dedicated to research, making it easier to schedule time on the machines.”

As important as access to the scanners themselves, the Human Imaging Unit connects researchers with expert radiology staff and faculty, making it possible for investigators to use the equipment regardless of their level of experience with human imaging.

In one example, the Human Imaging Unit helped develop imaging methods to evaluate how well the placenta is functioning in late pregnancy. “The researcher wanted to investigate the health of the placenta and how that is affecting the fetus in utero,” McKinstry says.

“So our staff helped him develop a protocol to measure placental morphology, size and chemical makeup for clues as to whether the placenta is ‘running out of gas’ and putting the fetus at risk. The investigator knew the question he wanted to answer, but he didn’t know how to use imaging to answer it.”

The scanning tools also let researchers image a beating heart in near real time; easily distinguish bone, soft tissue and fluid; and create two- and three-dimensional images. The equipment includes two MRI scanners, a CT scanner, a combined PET-CT machine and a PET-MRI system.

Because imaging is often a key bridge between animal studies and human application, the CCIR serves an important role in translating basic science from preclinical areas into clinical research areas. The CCIR is one of only five or six facilities in the United States that has a PET-MRI machine. Cutting-edge instrumentation like the PET-MRI, as well as the presence of multiple high-end imaging systems all in close proximity, make the CCIR a world-class translational imaging research facility, says McKinstry.

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