UCSF scientists to receive two grants for personalized medicine research

UCSF scientists will receive two grants totaling $15.1 million over the next five years to expand their research into how genes affect an individual's response to medication and to strengthen a global network of researchers involved in these efforts.

The UCSF team is the largest recipient in a $161.3 million effort by the National Institutes of Health to expand a national collaboration of scientists known as the Pharmacogenomics Research Network (PGRN), with the goal of paving the way for personalized medication.

"The grants dramatically extend our ability nationwide and globally to make the promise of individualized pharmaceutical care for patients a reality," said Mary Anne Koda-Kimble, PharmD, who is dean of the UCSF School of Pharmacy in which two UCSF projects are housed. "We see so much variability in how patients respond to drugs. What a great day it will be when we have the tools to easily predict response and adjust treatment on a personal level."

Both UCSF projects will be led by Kathleen Giacomini, PhD, a pioneer in the study of pharmacogenomics - how an individual's genetics determine his or her response to medicines - and co-chair of the UCSF Department of Bioengineering and Therapeutic Sciences.

The UCSF grants include $11.9 million for research into the genetics behind membrane transporters, which control the absorption, distribution and elimination of many of the most commonly used drugs. This multi-disciplinary, multi-center grant funds pharmaceutical scientists, geneticists, clinicians and computational biologists at UCSF and other institutions to carry out research in personalized medicine.

The expanded research ranges from studies in cells to studies in patients. The lead clinical study, which will be carried out in collaboration with scientists in the Division of Research at Kaiser Permanente Northern California and Kaiser Southeast, will focus on the genetic factors that determine response to the anti-diabetic drug metformin in African American patients with type 2 diabetes.

The field of membrane transporter pharmacogenomics has undergone enormous growth over the last decade, Giacomini said, and it is expected to have a significant impact on our understanding of pharmaceutical therapies over the next decade as well. In fact, the field of pharmacogenomics is expected to see enormous change, she said.

"Thanks to breakthroughs in genome sequencing technologies and our growing understanding of genetic variation among individuals, there has never been a better time to propel the field of pharmacogenomics," said NIH Director Francis S. Collins, MD, PhD. "Through these studies, we are moving closer to the goal of using genetic information to help prescribe the safest, most effective medicine for each patient."

Giacomini also will oversee a $3.2 million grant under the NIH program, to continue and expand a Global Alliance for Pharmacogenomics. This alliance involves NIH funded scientists in the Pharmacogenomics Research Network and scientists from the Center for Genomic Medicine, Riken, Yokohama, Japan.

The alliance will focus on large genomic studies of drug response from many drug classes, including those targeting cancer, asthma, cardiovascular disease and diabetes. The goal of the alliance is to identify genetic markers that determine both therapeutic and adverse drug responses in multiple racial and ethnic populations. These markers can eventually be used to guide drug therapy.

"This research requires analysis of vast amounts of data that can only be tackled through collaborative efforts among scientists and clinicians in many institutions," Giacomini said. "The global alliance will enable us to bring together the best and brightest in this field, from around Japan and the U.S., to achieve the goals of personalized medicines."

The new awards include 14 scientific research projects and seven network resources, and build upon a decade of work in this area funded by the NIH. Spearheaded by the NIH's National Institute of General Medical Sciences (NIGMS) and launched in 2000, the PGRN already has identified gene variants linked to medication response for different cancers, heart disease, asthma, nicotine addiction and other conditions.

The expanded network will continue research in these areas and move into new ones, including rheumatoid arthritis and bipolar disorder. Network scientists also will develop novel research methods and study the use of pharmacogenetics in rural and underserved populations.

The funds will benefit scientists by offering deep DNA sequencing capacity by partnering with experts in the field; providing statistical analysis expertise; developing standardized terminology for pharmacogenomics research; piloting ways to learn about pharmacogenomics from de-identified medical records; and continuing and expanding a 2-year-old international collaboration with the Center for Genomic Medicine at the RIKEN Institute in Yokohama, Japan.