Pharmacogenomics Profiles


There are molecular biologists, and biochemists, and immunologists. There are toxicologists, and pharmacologists.

But there are no pharmacogenomicists.

The field is too young and immature to warrant a job title. And most of the time, pharmacogenomics is one of a series of tools--albeit a crucial one--that researchers use to investigate how patients respond to drugs, and the mechanisms of drugs and drug interactions.

Charlotte McKee and Sally Usdin Yasuda can attest to that. Both transitioned into positions that rely in part on pharmacogenomics. McKee is associate director of experimental medicine for Wyeth Research in Madison, New Jersey, and Yasuda is a pharmacologist in the Food and Drug Administration's (FDA's) office of clinical pharmacology and biopharmaceuticals in Rockville, Maryland.

Tool for high-quality patient-based research

McKee began her career as a pulmonologist at Brigham and Women's Hospital and Harvard Medical School in Boston, where she investigated the immunology of lung transplants. "The basic science of the immunology of transplants was incredibly interesting to me. It encapsulates the immunology of all diseases," she says.

At Brigham and Women's, she led clinical trials in lung transplants and found herself happily pursuing a career in "translational" research that applied basic science to clinical studies.

Despite no previous interest in industry, she moved to Wyeth last year after a recruiter approached her about a similar position at another company. "It was a chance to do high-quality patient-based research--it was not only an opportunity, it was really a mandate. The people described to me as potential colleagues were highly trained ? it was a very different world from what I thought industry was," she recalls.

Now at Wyeth, McKee is searching for biomarkers of disease progression or drug activity or toxicity. Pharmacogenomics is one of the tools she uses to do that. "We specifically look at cutting-edge or novel technologies ? our task is to integrate them into drug development." The team typically conducts observational studies. One current study looks at the pharmacogenomic profile of asthma patients and healthy controls, and these data will serve as a reference database for future studies. Analysis may also reveal asthma drug targets. Rather than measuring genetic changes directly (such as single nucleotide polymorphisms, otherwise known as SNPs), McKee and her group typically do RNA expression profiles on patients to see what genes are being expressed.

Studies of drug interactions

Yasuda's career has also followed a winding path. She started out as a pharmacologist, with a longstanding interest in drug mechanisms. She is also interested in bridging basic and clinical science. "Clinical pharmacology is a very small discipline. But it's considered a bridge discipline, and that's exactly what I like about it."

After receiving her PharmD degree at the Philadelphia College of Pharmacy and Science, Yasuda became an instructor and eventually an assistant professor at the Georgetown University Medical Center, where she conducted phenotypic studies to determine how well individuals metabolized certain compounds. In the days before fast and cheap molecular biology techniques, she and her colleagues conducted receptor-binding studies, analyzing patients' plasma for signs of the drug or an active (receptor-binding) metabolite.

But the field began to change as molecular biology techniques became widespread, and an incident with the antihistamine drug Seldane (terfenadine) in 1992 galvanized the research community to pay more attention to drug interactions. A patient who had been taking Seldane and the antifungal drug Nizoral developed heart palpitations and a life-threatening arrhythmia. The drug interaction interfered with drug metabolism and led to an accumulation of Seldane to dangerous levels. The side effect is rare, but in 1998, Hoescht Marion Roussel and Baker Norton Pharmaceuticals voluntarily removed the drug from the market when safer alternatives became available.

The study of drug interactions and ultimately pharmacogenetics then took off. "We all of a sudden learned a lot more about drug-induced toxicity and we learned more about drug interactions, and the advent of molecular biology tools all kind of happened at the same time to make people a lot more aware," Yasuda says.

About a year ago, she joined FDA, where she reviews pharmacokinetics for neuropharmacologic drugs. Some of her work involves pharmacogenomics, but not all. FDA is only beginning to get up to speed on pharmacogenomics and does not require submission of such data for new drug approvals. But such data will likely become a standard part of the approval process in the future, and Yasuda and others are working to lay the regulatory groundwork.

"What I think is really neat is I get to see drug discovery and drug use from every point of view, because I've been a pharmacist dispersing drugs and a clinical pharmacologist [investigating] how they work in people, and I've done research at the bench. Now I get to see the synthesis of everything," she says.

Read the companion article Personalized Drugs, Personalized Careers, also part of this Next Wave feature.

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