DeRisi is not a physician, but his work with UCSF virologist Don Ganem, also an HHMI investigator, has tremendous clinical potential. It’s “bench-to-bedside research at its very best,” says UCSF chancellor and Nobel laureate J. Michael Bishop.

After graduating in 1992 from the University of California, Santa Cruz, with an undergraduate degree in biochemistry, DeRisi went to Stanford University to do graduate work in the lab of HHMI investigator Patrick O. Brown. At that time, DNA microarrays were so new that the National Institutes of Health had rejected Brown’s initial requests to develop the technology. But one of Brown’s favorite phrases is “blast ahead,” and he knew that microarrays were going to be important so he pieced together other funding to work on them.

Analogous to mailboxes in an apartment building, DNA microarrays consist of thousands of distinct DNA fragments attached to a glass slide. DNA samples that a researcher wants to identify are tagged with fluorescent labels and washed over the slide. Just as letters are sorted into mailboxes, DNA pieces in the sample stick to matching DNA fragments on the slide, allowing the unknown DNA to be identified.

Although DeRisi went to Stanford to study retroviruses, he was soon swept up in the scientific and engineering challenges of microarrays. “The project I was doing required high-density arrays, and no one was going to make them for me,” he says. After building and programming a robot that attached the DNA fragments to the slide using precision-guided metal pen tips, DeRisi and the other members of Brown’s lab used the device to achieve a number of notable firsts. They were the first research group to look at the activity of all genes in yeast simultaneously, for example, and they were the first to use microarrays to explore global gene expression in human cancers.

Brown and DeRisi found they had much in common. DeRisi is a onetime black belt in aiki-jujitsu; Brown is a marathoner. Both are devoted to open-access publishing of scientific articles; Brown was a cofounder of the Public Library of Science, through which DeRisi publishes many of his papers. And both are ardent proponents of making microarrays as inexpensive and accessible as possible. DeRisi has posted instructions on his Web site for how to build a microarrayer, and he has taught highly popular summer courses at Cold Spring Harbor Laboratory in New York and UC Santa Cruz on constructing and using microarrays.

DeRisi’s expertise in molecular biology, bioinformatics, and microarray technology made him a hot prospect, and a UCSF Fellows position was quickly followed by a faculty appointment. DeRisi used his new position to launch a major study on malaria. By tracking the expression of genes of Plasmodium falciparum—the parasite that causes the most severe from of the disease in humans—over time, DeRisi and his colleagues have uncovered particular genes that turn on and off in sequence as P. falciparum attacks and destroys blood cells. He is working on tests of new antimalarial drugs to see if they interfere with the process.

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