UCSF set to transform itself into engine of translational research

By Jennifer O'Brien

Signaling a watershed moment in the evolution of UCSF, the National Institutes of Health today announced that the University has received funding for a major new venture designed to accelerate the pace at which scientific discovery is translated into patient care.

The highly competitive funding mechanism, known as the Clinical and Translational Science Award, is being issued under the “NIH Roadmap,” a strategic plan unveiled by NIH Director Elias A. Zerhouni, MD, in 2002 to drive the future of biomedical research.

Universities were encouraged to develop proposals to establish departments, centers or institutes, funded over five years, that would support innovative and far-reaching approaches for carrying out translational and clinical science. Seven universities, including UCSF, received funding for a full institute.

The UCSF Institute will be supported with more than $100 million over a period of five years.

The NIH funding mechanisms will support a nationwide consortium of departments, centers and institutes, beginning with 12 academic medical centers. When fully implemented in 2012, approximately 60 will be linked in the common effort.

“The development of this consortium represents the first systematic change in our approach to clinical research in 50 years,” said Zerhouni. “These sites will serve as discovery engines that will improve medical care by applying new scientific advances to real world practice.”

The UCSF Clinical and Translational Science Institute will extend across all four schools - Dentistry, Medicine, Nursing, Pharmacy - and its graduate division. It is designed to create an enterprise that promotes research and education in translational and clinical science at UCSF, in partnership with its training hospitals—UCSF Medical Center, UCSF Mount Zion Medical Center, San Francisco General Hospital Medical Center, San Francisco Veterans Administration Medical Center - and its affiliated institutions, including the J. David Gladstone Institutes. The enterprise also will include Children’s Hospital Oakland Research Institute, the Blood Systems Research Institute of San Francisco, Kaiser Permanente, Division of Research, and the larger health-care community.

“This is an extraordinarily exciting time in the history of medicine,” says UCSF Chancellor J. Michael Bishop, MD. “There have been tremendous advances in understanding the molecular, genetic and cellular basis of numerous diseases.

“But the translation of this knowledge into therapies for patients has often been slow. UCSF has been working to develop the mechanisms necessary to address this gap for a number of years, and is committed to making itself into a leading center for translational research. The CTSI will galvanize this effort.”

The Institute will be directed by Joseph “Mike” McCune, MD, PhD, UCSF professor of medicine, chief of the division of experimental medicine and the principal investigator of the grant. Co-directors of the Institute will be Deborah Grady, MD, MPH, UCSF professor of epidemiology and biostatistics and of medicine, vice chair of the Department of Epidemiology and director of the UCSF Women’s Health Clinical Research Center; Dan Lowenstein, MD, UCSF professor of medicine, vice chair of the Department of Neurology and director of the UCSF Epilepsy Center and Director of Physician-Scientist Training Programs for the School of Medicine; and Joel Palefsky, MD, UCSF professor of medicine and program director of the UCSF General Clinical Research Center.

“Our goal is to find more efficient ways to move basic research findings into the clinic,” says McCune. “We hope that the CTSI will serve to bring better health care to more people, more quickly.”
The evidence suggests the will and spirit are there, he says.

“The proposal that we submitted to the NIH reflects substantive input from more than 200 faculty members at UCSF and at our partner institutes in the Bay Area. These are all people who are working in the area of clinical and translational research now, and who will serve as a nidus for the effort that the CTSI will nurture going forward.”

The goal of translational research is to take the discoveries made at the lab bench and to determine how they might be applied to preventing, managing, or curing diseases in people. This process typically requires studies in animals or other laboratory-based experimental systems that can be used to model human disease as well as studies in humans. It is one that requires an elaborate infrastructure that academic medical centers - the primary engines of biomedical research discovery in the United States - traditionally have not had. The final step is to develop and assess methods to encourage adoption of clinical research findings into community practice. 

“The discovery process of modern science has been remarkably robust,” says McCune. “Such success only highlights the need to find better ways to move these discoveries into practical application. This is what the CTSI is meant to do.” 
Translational and clinical research has been hindered on several fronts, says McCune. Many basic scientists, who carry out studies in cell culture and animals, do not have the training to design the particular types of animal model studies needed to test the safety and efficacy of experimental therapeutic strategies they may have developed. Likewise, many clinical researchers, who carry out their studies in patients, do not have seamless access to findings that have come out of the research lab. Finally, there has not been an infrastructure in place to facilitate an effective continuum of research from bench to bedside to community. In all cases, the infrastructure to carry out the work has been under-resourced and/or incomplete, according to McCune.

To address these challenges, the UCSF Institute is establishing 13 interrelated programs, to be led by senior scienists representing diverse disciplines. These programs are designed to:

  • build on UCSF’s premier training programs - increasing the number of trainees from diverse disciplines and improving the quality of their training in clinical and translational research methods.
  • support researchers newly trained in translational and clinical research—improving and integrating existing infrastructure to enhance the design and
  • implementation of clinical and translational studies, and fostering collaborations to achieve a diverse spectrum of high quality, original research.
  • enhance career development of clinical and translational researchers—by providing mentoring and opportunities to catalyze original research, and by changing the academic culture to appropriately reward multidisciplinary collaborative work.
  • create a “virtual home” providing communications to simplify collaboration, to provide an optimal informatics matrix for conducing innovative research, including use of a web-based portal/Internet/broadband.

The potential of translational research is clear. UCSF and Stanford University scientists co-discovered the techniques of genetic engineering in the 1970s, and pioneered the use of these techniques to create medically useful drugs, such as insulin, spawning the biotechnology industry.

A UCSF scientist discovered the protein surfactant, essential for keeping the lung inflated, in the 1960s, and a UCSF team developed a synthetic form of the protein to treat premature babies whose immature lungs don’t produce it.

And today, numerous translational efforts are under way throughout UCSF. They are exemplified in the work of Joseph DeRisi, PhD, a pioneer of microarrays who has established collaborations using the tool to explore the possible role of viruses in cancers, asthma and a host of other diseases; James McKerrow, PhD, who is also focused on diseases of the developing world; John Kane, MD, who is searching for genes associated with such disorders as diabetes, arteriosclerosis and hypertension, and pediatrician Michael Cabana, MD, MPH, who is leading a large, NIH-funded trial aimed at determining if “good bacteria,” or “probiotics,” normally found in the human intestine and many common foods (including yogurt), can be used to prevent the development of asthma in children.

As discussed in the reviews of the proposal received from the NIH, “The spirit of the UCSF CTSI is emblematic of the innovation, transformation, and creativity seen in the Bay Area. This effort will benefit from an environment that is tolerant, vibrant, receptive, and risk taking.”

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the health professions and life sciences, and providing complex patient care.