Research on errors of cell division may yield new cancer targets

David Pellman, MD

David Pellman, MD, a pediatric oncologist at the Dana-Farber Cancer Institute and Children's Hospital Boston, is one of 56 scientists just selected as an investigator of the Howard Hughes Medical Institute (HHMI), a non-profit medical research organization that ranks as one of the nation's largest philanthropies. Highly sought after, HHMI appointments provide creative biomedical scientists with the opportunity to tackle their most ambitious, risky research plans. Pellman was chosen from among 1,070 applications submitted in a nationwide competition. Overall, HHMI is committing more than $600 million to support the 56 new investigators' first five-year terms.

Pellman, in his laboratory at Dana-Farber, conducts basic research in cancer, studying aneuploidy, a condition in which a cell has too many or too few chromosomes. Aneuploidy is known to be an important prognostic factor in such cancers as childhood leukemia and neuroblastoma. Working with yeast and mouse models, Pellman and colleagues are investigating how aneuploidy occurs as a result of errors in mitosis, or cell division, and how aneuploidy leads to genome instability (an increased tendency to develop gene mutations) and ultimately to cancer. The team recently showed that polyploidy, or increased sets of chromosomes in a cell, increases the likelihood that specific gene mutations will lead to cancer — an old idea that had never been tested and demonstrated directly.

Pellman hopes to develop new treatment approaches that exploit the biological differences between normal and aneuploid cells, since aneuploid cells may be vulnerable to drugs that aren't harmful to normal cells or tissues.

The HHMI appointment will allow Pellman to dig more deeply into the effects of aneuploidy, polyploidy and make the needed connections to human cancer. Appointment as an HHMI investigator provides a level of support much greater than a research grant for an individual project — giving a rare freedom to explore and follow ideas through to fruition — even if that process takes many years.

After medical school at the University of Chicago, Pellman completed his medical internship and residency at Children's Hospital Boston in the 1980s. He did research fellowships in cell division and yeast genetics at the Whitehead Institute for Biomedical Research, while holding appointments in oncology at Children's and Dana-Farber. He returned to complete his clinical oncology training and join the faculty in the Department of Pediatric Oncology at Children's and Dana-Farber in 1995.

About Dana-Farber

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

About Children's Hospital Boston

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.

About the Howard Hughes Medical Institute

The Howard Hughes Medical Institute, a non-profit medical research organization that ranks as one of the nation's largest philanthropies, plays a powerful role in advancing biomedical research and science education in the United States. In the past two decades HHMI has made investments of more than $8.3 billion for the support, training, and education of the nation's most creative and promising scientists.