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A Faithful Translation

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It may contain multitudes, but Pennsylvania's Institute for Translational Medicine and Therapeutics is certainly not about to contradict itself. The two-year-old institute is, however, fostering an environment where researchers from clinical and basic research sides of the fence can merge their expertise to address questions across the biological spectrum –– from single analytes to entire patient populations.

According to Garret FitzGerald, ITMAT's director and a professor of pharmacology, the germinal idea for the institute grew out of discussions between the University of Pennsylvania's medical school dean and faculty. In the course of these strategic planning talks, many faculty voiced interest in opportunities presented within the broad area of experimental therapeutics. FitzGerald, who was then director of Penn's own center for experimental therapeutics, spent a sabbatical year thinking about the best way to address the objectives that came out of the faculty-wide talks while also building on what had already been developed so far. He came back and pitched the idea for ITMAT.

The idea was catalyzed by observation: FitzGerald saw the need for more investigators versed in model systems, mechanism-based clinical investigations, as well as human pharmacology. "I think the deficit in human capital is a real weakness," he says, pointing to the current lack of truly interdisciplinary scientists in both academia and the pharma industry. Thus, the institute began with the mission to increase the number of people who could operate in a translational setting, while diminishing the hurdles that these investigators confront.

It is to these ends that ITMAT has created space, generated funding, and directed recruitment and education efforts. Early on in its planning, FitzGerald says, it was agreed that ITMAT would not be a virtual entity –– it was always intended to provide a physical base for researchers across the translational divide. The bricks-and-mortar enterprise was initially housed in Penn's school of medicine, and its focus started with projects that spanned from proof-of-principle work in model systems to studies of drug mechanisms and dosing in humans. At this point, ITMAT's field of view also includes chemistry and drug discovery, as well as clinical application of research discoveries.

The enhanced research remit followed on the expansion of the institute itself. Nine months after ITMAT officially launched, the NIH issued a call for applications to its Clinical and Translational Science Award program. "We were interested to read that [RFA]," FitzGerald says, "because to a substantial degree, it read like we'd written it." They hadn't, of course, but they had anticipated the NIH by creating an academic home for translational projects, subsuming existing general clinical research centers, and charting a broad research mission. In the course of applying for the award, ITMAT engaged investigators not only within Penn, but also at the Children's Hospital of Philadelphia, the Wistar Institute, and the University of the Sciences in Philadelphia. By the time the award was made, ITMAT had become a trans-institutional endeavor.

Next Fold of the Future

With funding in place, ITMAT plans to establish several new centers devoted to different branches of translational research. The general clinical research centers of Penn and CHOP will be integrated to form a translational research center that will shoulder many initiatives contained in the CTSA proposal, FitzGerald says. Other new centers going up will be devoted to translational issues in personalized medicine, imaging, bioinformatics, and chemical biology. Each of these centers will have components for research, education, and service, and all will encourage external collaborations.

The educational aspect of centers will revolve around the institute's degree program in translational research. The masters program currently has about 25 people enrolled, and the institute expects this number to grow substantially. "We're aiming to set aside about a fifth of our medical school entrants dedicated to people who take this MTR degree," FitzGerald says. ITMAT is also reaching out to undergrads by introducing students at 600 schools to the concept of translational research.

While the centers will bring lines of complementary research together, ITMAT's programs are designed to foster study areas that are nascent or nonexistent at home institutions. Targeted therapeutics and systems biology are two examples that are already running. "Ideally, at the end of the day, these programs might develop in ways that they eventually mature into being centers," FitzGerald says.

Eleven new cores are planned to complement the upcoming centers. In its first year of operation, the institute developed a bioinformatics core and took ownership of existing facilities that were relevant to its mission.

The proteomics core is one such adoptee. Ian Blair, the core's scientific director, developed the facilities under the aegis of the Penn Genomics Institute. The core provides services and also participates in collaborative research projects with ITMAT's investigators. In order to make headway on quantitative proteomics projects, the core relies on a battery of tools, including a DIGE system, a MALDI/MS/MS instrument, a Q-Star mass spec, as well as an LTQ-FT outfitted with an HPLC system.

Proteomics doesn't occur in a vacuum at ITMAT, and Blair says that the institute's bioinformatics core has been "incredibly helpful in bringing cutting-edge proteomics to fruition." For instance, Blair's team has created an innovative technique to label and quantify 600 proteins in a single run via high-resolution selective ion monitoring. With 20 cell lines already labeled, the proteins are accessible, but they have to be found. For this, Blair is working with the informatics group to identify proteins, peptides, and metabolites in silico.

Blair's collaborative projects are varied, and include investigations to clarify the proteomics of premature birth, ozone-induced asthma, and platelet function. He's also at work to develop a biomarker core, which is set to apply systems approaches to biomarker discovery.

The work of investigators at the institute is not bound by discipline or department, and this suits Blair just fine. He notes that translational medicine, because it is not disease-specific, opens the door to leveraging many resources to help answer questions both basic and clinical. "We're very lucky to have the institute established to do all of this," Blair says. "In some ways, we're more limited by our imagination than we are by technology, which is a very strange place to be."

Name: Institute for Translational Medicine and Therapeutics
Host: University of Pennsylvania
Director: Garret FitzGerald
Launched: January 2005
Alliances: Children's Hospital of Philadelphia, the Wistar Institute, and the University of the Sciences in Philadelphia
Faculty: ITMAT does not appoint faculty, but rather draws researchers from allied institutional departments. There are roughly 150 members involved, and some cross-appointed faculty are housed in the institute itself.
Funding stats: The NIH has invested roughly $70 million in ITMAT through its Clinical and Translational Science Award consortium, while partner institutions have given an additional $30 million.
Centers: ITMAT has plans afoot to launch centers in translational research, personalized medicine, imaging, bioinformatics in translation, and chemical biology.
Research programs: Neurotherapeutics, systems biology, and targeted therapeutics.
Core facilities: Eleven cores are planned to serve the upcoming centers. There are core facilities already in place for bioinformatics, proteomics, and an investigational drug service.

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