He trolls genome for cancer clues

When Levi Garraway heard that his father was dying of prostate cancer, he decided to do something about it. At the time Garraway was writing his PhD dissertation on infectious diseases.

"My core interests shifted," says Garraway, now an assistant professor in the Department of Medical Oncology at the Dana-Farber Cancer Institute and a physician at Brigham and Women's Hospital. "Instead of reading about infectious diseases, I started spending my time reading about prostate cancer. It was very distressing to see how ineffective therapeutics were."

That was in 1995. Today, he's an associate member of the Broad Institute, a research collaborative dedicated to applying genomics to diseases such as cancer. Last week, he won a "new innovator" award from the National Institutes of Health, worth $1.5 million over five years.

"The big premise that underlies our work is that cancer is a disease of the genome," says Garraway, 39. "What goes wrong in a cancer cell? The genome is deranged, the DNA is mutated. But embedded within those chaotic changes are answers."

Through the use of advanced computing techniques and by mining data from the human genome project, Garraway and his colleagues are trying to identify the exact genes that mutate in specific cancers and combine those profiles with traditional lab experiments. The goal is to develop "targeted therapeutics." In other words, personalized medicine. "By understanding what gets perturbed by alterations in the DNA, we can be intelligent about targeting the cancer. The idea is to say, here's your tumor, and we'll intercept exactly what's gone wrong."

Garraway cites drugs like Tarceva for lung cancer, and Gleevec for leukemia, saying that some of the biggest successes in cancer treatment are coming from a gene-based approach to research.

Dr. William Hahn, an associate professor at Harvard Medical School and researcher at the Dana-Farber Cancer Institute, calls Garraway "a rising star," adding that his work on melanoma has contributed significantly to the understanding of the disease.

Garraway's lab chose melanoma as a model for working on genetics-based therapeutics because the cells grow easily in a tissue-culture dish. These laboratory cells are remarkably faithful in mimicking the behavior of cells in a patient - a rare stroke of luck in oncology. Prostate cancer cells aren't as cooperative, but Garraway is undeterred.

"There's no way I could let go" of researching prostate cancer, he says. "It's too close to home."

It was because of his father, a plant biology professor at Ohio State University, that Garraway got interested in science in the first place; he recalls childhood visits to garden plots to till beans and carrots, watch the shoots, and wonder how they sprouted. In high school, he hung around the university lab and helped with experiments. Garraway said his father, who died in 1999, "had a passion for inquiry."

Personal loss isn't Garraway's only motive. Prostate cancer is particularly dangerous for African-American men, among whom it is both more prevalent and, possibly, more severe than among other populations. As an African-American, Garraway is particularly eager to find a cure.

"It's increasingly evident that there's a difference in cancer biologies between ethnicities," he says, adding that most clinical trials are biased towards Caucasians. Studying those differences is a burgeoning field of research, he says, and one that's barely begun to bear fruit. The challenges are enormous, but so are the potential rewards.

"Cancer research isn't for the faint-hearted," says Garraway. "But there's real promise for change."

Hometown: Newton.

Family: Wife Gisele, 37, son Dwight, 5, daughter Darena, 2.

Hobbies: A continuing attempt to break 100 in golf. Watching college football on television. "Ohio State, of course. I grew up 15 minutes away from the stadium."

Research philosophy: "I feel that the right way to do cancer research is to be guided by genomics."

All in the family: Garraway's sister, Isla, is a urologist at UCLA who has, like him, devoted part of her career to prostate cancer research. They were featured together this year in a Father's Day spot on CBS Evening News.