David Pellman, MD, has been named one of 56 new Investigators by the Howard Hughes Medical Institute (HHMI), one of the nation’s largest philanthropies and supporters of biomedical research.

Pellman, a pediatric oncologist at Dana-Farber and Children’s Hospital Boston, will receive substantial financial support to pursue innovative research with fewer constraints than is customary with short-term federal funding.      

HHMI Investigators are appointed for five-year renewable terms. HHMI, based in Chevy Chase, Md., invests some $700 million annually in its investigators – about 300 at any one time – who remain in their home institutions. The organization holds nationwide competitions to select scientists who are relatively early in their careers, highly productive, and pursuing groundbreaking research. The current group of HHMI investigators includes 12 Nobel Prize winners and 122 members of the National Academy of Sciences.

“It’s a great honor for the lab, and a recognition of the work we’ve done in the course of the last 10 years,” said Pellman. Other HHMI investigators at Dana-Farber include Stuart Orkin, MD, Todd Golub, MD, and William Kaelin, MD.

Pellman joined the DFCI and Children’s faculty in 1995. Previously, he had research fellowships in cell division and yeast genetics at the Whitehead Institute for Biomedical Research in Cambridge, while holding appointments in oncology at Children’s and Dana-Farber.

In his basic research work, Pellman proved an old idea about cancer using contemporary methods. A hallmark of many cancer cells is that they are aneuploid, meaning that their nuclei contain too few or too many chromosomes. It had been hypothesized that an important route to becoming aneuploid was for cells to pass through an unstable intermediate phase where the whole genome was doubled.

“The idea that the doubling of the genome would contribute to tumor development is one of those ideas that’s been out there, would get revisited every ten years or so, but would then be forgotten,” says Pellman.

Working with yeast and mouse models, he and colleagues are investigating how genome doublings (also known as polyploidy) affect the stability of the genome, resulting in aneuploidy and ultimately cancer. In broader terms, he hopes to determine if polyploidy and aneuploidy accelerate the pace of evolution – a fundamental property of incipient cancer cells. Pellman hopes to develop new treatment approaches that exploit the biological differences between normal and aneuploid cells. The latter may be vulnerable to cancer drugs that aren’t harmful to normal cells or tissues.

Pellman says his research findings are helping him and his colleagues arrive at new ways of thinking about cancer that could have important longterm clinical payoffs.

Inside the Institute, May 28,2008 Volume 13, Issue 10