Now that the human genome has been sequenced, scientists face the daunting task of using the data to treat and possibly cure a whole host of human diseases. Some of the greatest promise for revolutionizing medicine using the new human genetic data lies in the design and improvement of prescription drugs. Among those at the forefront of this effort is UCSF's Kathy Giacomini, professor and chair of biopharmaceutical sciences in the School of Pharmacy.

Giacomini heads a project that revolves around the relatively new field of pharmacogenetics, the study of how genes affect the way people respond to medicines. As stated by the National Institute of General Medical Sciences (NIGMS), the ultimate goal of pharmacogenetics research is to tailor medications to a person's unique genetic makeup, so that they are safer and more effective. Through NIGMS, the National Institutes of Health funds an initiative involving twelve research centers across the country called the Pharmacogenetics Research Network.

Giacomini serves as principal investigator for the network's Pharmacogenetics of Membrane Transporters, a study that began in 2000. It looks at how drug response is affected by differences in the genes that code for the cellular "gatekeeper" molecules that interact with a third of the most commonly used prescription drugs. The four-year, $12 million membrane transporter project includes fifteen UCSF investigators as well as researchers at UC Berkeley, UCLA and Stanford University.

Moving to Mission Bay

Giacomini, who will be among the researchers moving to UCSF's Mission Bay campus, says the move will facilitate new collaborations and increase the productivity of her lab. "I'm very excited about going to Mission Bay because it brings together researchers who are working on all aspects of human genetics. I imagine that it will be a very exciting place for my research. There I'll be in an integrated program with a core facility and human geneticists close by. Right now, we are all over UCSF and the core facility is two buildings away. For human genetics studies you need large cores to support your research."

Many areas of research are relevant to the study of human genetics, Giacomini says. Mission Bay will be home to many researchers who can inform and collaborate on Giacomini's current and future work. For example, Giacomini says that the presence of those using animal models to study genetics will serve to ground the work by her and others into aspects of human genetics. In addition, members of the Institute for Quantitative Biomedical Research (QB3) can bring the latest in bioinformatics, molecular modeling and imaging to bear on pharmacogenetic studies. "It's a big plus to have researchers like that who can interact with human geneticists," Giacomini says.

Despite her excitement about working with her new Mission Bay colleagues, Giacomini is determined to stay linked with her colleagues at all UCSF sites. She will maintain a group working on clinical studies at Parnassus. She supports plans to centralize DNA banks at SFGH and link them via the Internet to other parts of the campus. And, she hopes to sponsor initiatives like video-conferencing meetings and seminars. "These links are important, especially in research areas that have both clinical and basic research foci."

All in the Family

Giacomini's passion for science was fostered by her family as she grew up in Colorado. Her maternal grandfather was a physician, her father is a geophysical engineer and her mother, a Filipina who once attended dental school, always had an interest in the health sciences.

Giacomini attended the University of Colorado and the University of Houston as an undergraduate. At first, she majored in pharmacy, but quickly realized she would not become a practicing pharmacist. "I got quite excited about science when I started to do research projects," she recalls. Getting into the laboratory and experiencing the thrill of discovery sealed her fate. "There were so many unanswered questions and there's so much we still don't know."

After college, Giacomini earned her doctorate from the State University of New York, Buffalo. She then went to Stanford for postdoctoral studies before coming to UCSF in 1981, where she has fallen in love with teaching. "That is something that's a real plus." Giacomini teaches graduate students in the sciences as well as those in the School of Pharmacy.

She holds joint appointments as a professor of pharmaceutical chemistry and cellular and molecular pharmacology.

When she's not in the lab or the classroom, Giacomini is either enjoying the company of her family or playing tennis. Her husband, John, is a cardiologist at Stanford, where eldest son Craig is a cardiologist at Stanford, where eldest son Craig is a senior and his younger brother Nicholas will start classes in the fall of 2003. The couple's 10-year-old daughter, Alexandra, "is just a regular happy kid."

For women in science, balancing work and family is no easy task, Giacomini says. She jokes about having planned all three of her pregnancies around the writing of grant proposals. But having a family, she says, helps her to focus on research. "I don't have a lot of off hours. I've gone out of my way to say no to a lot of things."

Of Genes and Drugs

Judging by the enormousness of the transporter project, it would seem that Giacomini has said "no" to very little. It is a complex project involving three major areas of research:

• The sequencing of DNA that codes for 25 different membrane transporter genes in 247 people, which allows for the identification of genetic variants. The group is searching for these variants in 100 African Americans, 100 Caucasians and a number of other racial and ethnic groups as well.
• Characterizing the behavior of these variants in cells to determine the effects of genetic variation and identifying variants that may influence the way a person with that variant responds to a drug.
• Conducting human clinical trials, testing drug levels in people with known variants. A cohort of nearly 500 healthy volunteers from four different ethnic groups living in the San Francisco Bay Area have already donated their DNA and agreed to take part in future studies.