Another new HHMI investigator, pathologist Arul M. Chinnaiyan of the University of Michigan Medical School, also aims to devise novel treatments through a better understanding of the basic events that lead to a disorder—in this case, solid tumors such as cancers of the breast, colon, lung, and prostate.

Most solid tumors have traditionally been thought to result from mutations that affect one or more growth-regulating genes in the cell. This mechanism is different from what happens in blood cancers—such as leukemias and lymphomas—which occur when chromosomes inappropriately swap pieces of genetic material—a process called translocation. The "fusion" genes that result can spur rapid and uncontrolled cell division, as in chronic myelogenous leukemia (CML), which is caused by the fusion event involving the two genes Bcr and Abl. That finding led to targeted drugs, such as Gleevec, that have dramatically improved survival of patients with CML.

In 2005, when Chinnaiyan used DNA microarray technology and powerful computational tools to analyze biopsies from patients with prostate cancer, he was stunned to find that almost 80 percent exhibited translocation. The fusion gene resulted when a male hormone-regulated gene, TMPRSS2, joined certain DNA transcription factors to create an overactive "on" switch for growth-stimulating genes in prostate cells.

Because that discovery did not fit current dogma, "we didn't believe our result at first, and we had to carry out further studies before we convinced ourselves it was true," Chinnaiyan recalls. "We think this is the causative lesion—it's the 'Bcr-Abl' in prostate cancer."

The discovery inspired Chinnaiyan's current ambitious plans to use high-throughput search methods to find fusion genes he believes may be the key to other solid tumors as well. "We're working diligently in breast cancer, because we believe there is an estrogen-regulated gene fusion comparable to the androgen-regulated gene fusion we found in prostate cancer," he says. By identifying gene fusions associated with these and other solid-tumor cancers, Chinnaiyan hopes to provide targets for new drugs that are more effective than current therapies.

What unites him with Rowitch, Engle, and the 12 other recent appointees is their calling as physician-scientists who spend their professional lives crossing the boundaries between the laboratory and the clinic, convinced that patient care informs and enhances their research. Says HHMI's Cech: "With the appointment of these new investigators—who will also serve as mentors for the next generation of patient-oriented researchers—and our early-career awards to physician-scientists, we are sending a strong message that HHMI is committed to supporting the people who perform this vital work."

FOR MORE INFORMATION: To read about the other new investigators, go to www.hhmi.org/news/por20071011.html. To learn about HHMI's early-career awards, visit www.hhmi.org/news/20070815.html.

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