The Hospital of the University of Pennsylvania and the Children’s Hospital of Philadelphia (CHOP) sit side by side on the south edge of campus. But a few years ago, when they launched a joint translational research initiative, the separation loomed like an ocean. The two hospitals have completely separate finances, and their research arms compete with each other. So getting them to collaborate, says Penn pharmacology professor Garret FitzGerald, was like “Franco-German rapprochement.”
FitzGerald is director of Penn’s Institute for Translational Medicine and Therapeutics (ITMAT), launched in 2005 to unite and expand clinical and translational research programs across the Penn campus, including those at the two hospitals. Last year, Penn was one of a dozen institutions awarded a National Institutes of Health (NIH)-sponsored Clinical and Translational Science Award (CTSA), a $68 million, 5-year grant. Penn is investing $30 million of its own money in the effort.
Despite some “bumpy bits” during negotiations between Penn and CHOP, says FitzGerald, “[we] have worked more and more together, and this has gone extremely well.”
Establishing research and training
Building infrastructure to support translational investigators is key. “The previous model before was, you do the whole thing yourself,” notes Carl June, director of translational research at the Abramson Cancer Center at Penn. But tougher regulatory requirements and more complex science now make that impossible. To help investigators, Penn employs clinical trial application specialists and has core facilities in everything from bioinformatics to proteomics, as well as a translational imaging center. Meanwhile, CHOP is constructing a new building that will support mouse model work–including small-animal imaging–which is essential for evaluating new cancer therapies.
Because the skills needed for translational science are so diverse, FitzGerald argues for a completely new “interdisciplinary” discipline. Penn offers a master’s degree in translational research and a joint MTR-Ph.D. program. In addition, Penn has a grant from the Howard Hughes Medical Institute in Chevy Chase, Maryland, to develop courses to expose Ph.D. students to clinical research to inspire them to find cures for diseases.
In terms of research experience, Penn offers seven fellowships for translational research, along with 12 offered through the CTSA, and five more fellowships through NIH T32 research training grants.
To encourage cross-disciplinary research, only researchers from different departments who haven’t worked together can qualify for a $150,000 transdisciplinary ITMAT seed grant. Six pairs of senior investigators won grants in the latest funding round.
Penn is trying to push translational research in nontraditional directions. One novel center is Personalized Medicine in Translation (PERMIT). This center will fund the expert staff and facilities needed to examine how genetic variants affect drug response and will give traditional clinical studies a new dimension by identifying which individuals are most likely to benefit or suffer side effects.
FitzGerald’s own lab worked out the likely mechanism of Cox-2 inhibitor cardiac toxicity, and PERMIT is designed to detect and individualize such problems before drug launch, not after. FitzGerald is now probing why people differ in their response to all nonsteroidal anti-inflammatory drugs.
As a postdoc in FitzGerald’s lab, Tilo Grosser played a big role in the Cox-2 work. He is now an assistant professor setting up his own lab at Penn, and he just applied for his first R01 grant. Grosser knows that a career in translational research is risky compared to basic science. “I am aware of the issues, particularly the [smaller] number of publications,” he says. “These studies take a lot of time.” Grosser points out that a single small clinical trial looking at drug-response variability could take 3 years, including patient screening and data analysis. And clinical research involves sharing credit, which could also devalue his accomplishments.
“I have seen several instances since I’ve been at [Penn] where promising translational researchers had to go back and just do basic research in order to assure their promotion,” says June. “That’s not good.” Grosser thinks that the breadth of clinical research opportunities at Penn, encompassing genomics, mechanistic work, and animal modeling, makes such career setbacks less likely.
Although tenure committees at Penn are still dominated by R01-type scientists, says FitzGerald, they are gradually taking into account the team contributions and lower publication rates among translational researchers. “That’s an ongoing issue,” June says.
Thomas Curran, a CHOP neurobiologist, cancer researcher, and ITMAT member, agrees that fears of failed clinical trials and nonexistent publications are real, but they shouldn’t be career killers. “First, if you have all of those concerns, you’re in the wrong job, because this is a risk-taking enterprise,” he says. “Second is, plan for success, never plan for failure. … Come into it with the attitude [that] whatever you do, you’re going to do the highest quality [work], and you’re going to be successful–recognizing there’s an element of doubt.”