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Translating research from mice to men

Medicine@Yale, 2014 - July August


The largest federal grant in the medical school’s history provides scientists with tools to move their research from bench to bedside

As both a psychiatrist and a neurobiologist, Christopher Pittenger, M.D., Ph.D., is interested in how biological changes in the brain contribute to such psychiatric conditions as obsessive compulsive disorder (OCD) and Tourette’s syndrome. In the lab, he wanted to investigate cellular and molecular abnormalities in the brain that are associated with disease—and to find out how these changes affected the behavior of his patients.

Pittenger, associate professor of psychiatry, of psychology, and in the Child Study Center, was able to translate his research from bench to humans thanks to support from the Yale Center for Clinical Investigation (YCCI).

Launched in 2006 as part of the medical school’s strategic vision to strengthen clinical and translational research, YCCI provides an array of resources to support research as well as a home for the training of the next generation of investigators. In 2006, the School of Medicine was among the first 12 institutions in the U.S. to receive a five-year Clinical and Translational Science Award (CTSA) of $57.3 million, the largest NIH grant in the school’s history. The CTSA has since been renewed for an additional $47.5 million. This funding, with additional support from the School of Medicine, has allowed YCCI to develop new and enhanced programs, resources, and services to advance biomedical research.

The number of research grant applications to the National Institutes of Health (NIH)—the largest source of funding for medical research globally—has increased by 72 percent since 2000, but in 2013, the success rate for established investigators applying for R01-equivalent awards was just 15 percent, according to the NIH data book. For first-time investigators the success rate was even lower—13 percent—an illustration of the difficulties young researchers face. Pittenger, also director of the Yale OCD Research Clinic, made this leap thanks to a 2009 YCCI Scholar award, which provided two years of research support for imaging studies on the neurotransmitter glutamate in OCD patients. “I didn’t know enough and didn’t have enough of a published track record to get major external grants in clinical research at that time,” he says.

The Scholar program is the cornerstone of the educational programs under YCCI’s umbrella and is particularly important to fulfilling its goal of nurturing investigators early in their careers. “Building the next generation of investigators is critical, and it’s the most efficient way of sustaining research excellence at Yale,” says Robert S. Sherwin, M.D., C.N.H. Long Professor of Medicine, chief of the Section of Endocrinology, and director of YCCI.

The program has proven to be a sound investment: so far, over 90 percent of the 88 Scholars who have received awards have remained in academic medicine, generating $157 million in independent funding and publishing more than 1,000 papers. “Without the YCCI award I wouldn’t have been able to grow the clinical side of my research program, which is now half of my research portfolio,” says Pittenger, who also serves as a mentor to younger colleagues embarking on research careers. YCCI oversees the Investigative Medicine Program, one of a handful of programs in the U.S. offering a Ph.D. in investigative medicine for physicians who have completed their clinical training, and has expanded it to include scholars in nursing, public health, and biomedical sciences who want to pursue research. YCCI also supports about a dozen medical students annually to take a year off to work on research projects.

Before YCCI was established, investigators and departments were largely left to their own devices, since the School of Medicine lacked a centralized facility that offered the know-how needed to put together grants and conduct research studies. “Investigators need infrastructure with one-stop shopping resources,” says Sherwin, who is renowned for his research on diabetes. “This is critical so that investigators are able to focus on the science and get help on the things we’re not really trained to do.” YCCI’s Office of Research Services helps both experienced and novice investigators throughout the research process, offering expertise in developing study protocols, navigating regulatory requirements, developing budgets, recruiting study volunteers, supplying nursing and other research staff, and providing quality assurance.

One example of how YCCI facilitates research is the biostatistical support offered through the Yale Center for Analytical Sciences (YCAS). Created in partnership with the School of Public Health in 2010, the more than 30 biostatisticians affiliated with the Center provide assistance with statistical analyses, a crucial element in successfully carrying out research. For 2008 YCCI Scholar Leora I. Horwitz, M.D., M.H.S., assistant professor of medicine, whose research on the transition of care when patients are discharged from the hospital has earned her a national reputation, YCAS biostatisticians were instrumental in helping her develop the statistical section of her NIH Career Development award. “Having that resource makes all the difference,” Horwitz says.

Since 2007, YCCI has also provided almost $3 million for 64 pilot awards that allow investigators to develop new scientific initiatives and compete successfully for further funding. Pittenger received a pilot award for research showing that a genetic mutation that disrupts the production of histamine in the brain is a cause of Tourette’s syndrome. “YCCI is a place where I was able to get funding for exciting ideas at an earlier stage than I could otherwise have gotten,” says Pittenger, whose research originally funded by his Scholar award led to a major NIH grant that is enabling him to continue his work on OCD.

The pilot program, just one example of the benefits of YCCI’s collaborative approach, has built its successes by leveraging existing resources and collaborating with other programs. For example, much of YCCI’s regulatory and administrative support structure is intertwined with Yale Cancer Center (YCC). The two centers have collaborated to support YCAS as well as equipment and faculty expertise in research cores utilized for cancer research and genomics; these cores require the investment of millions of dollars to purchase, maintain, and repair sophisticated instrumentation.

YCCI has also worked with YCC and Yale-New Haven Hospital on an ambitious informatics program to support research that includes the implementation of both an electronic medical record and a clinical research management system across the entire Yale New Haven Health System, allowing researchers access to clinical data and improving the efficiency and quality of research studies. The integration of the two systems has helped improve planning for clinical studies, enabled easier access to potential patient populations and disease registries, and improved the research experience for study participants.

“In an era of shrinking NIH budgets it’s important to efficiently utilize limited resources,” says Sherwin. “There’s no doubt that our philosophy of partnership has served us well.”