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Our laboratory aims to understand normal cell division mechanisms and to discover cell division defects that are unique to cancer cell. We take a range of approaches including genetics, functional genomics, biochemistry and live cell imaging. There are ongoing projects using yeast, tissue culture cells, and genetically engineered mice.
Our work on cytoskeletal dynamics is focused on the mechanism of chromosome segregation in normal cells and cancer cells. We are particularly interested in how the microtubule and actin cytoskeletons interact and how cell cycle signals remodel these cytoskeletal systems. For example, we have recently uncovered a mechanism by which actin organization and the adhesive microenvironment of cells influence chromosome segregation. We study how centrosome amplification in cancer cells impacts cellular adhesion, cell migration, and tumor invasion. We have discovered new drug targets that kill cancer cells because of their centrosome amplification. We have defined cytoskeletal mechanisms that control polarized cell growth, asymmetric cell division, and cytokinesis. We use biochemical and imaging approaches to understand these processes at a mechanistic level.
We are also interested in how aneuploidy (abnormal chromosome number) and polyploidy (increased sets of chromosomes) impact on tumor biology. We have developed new methods to generate human cells with specific cancer-associated trisomies and are studying how these trisomies impact tumorigenesis. We discovered that failure of cytokinesis, which doubles the number of chromosomes and centrosomes, promotes tumorigenesis, using a mouse breast cancer model. We recently identified a mechanism by which errors in mitosis cause DNA breaks. These findings may explain the recently discovered phenomenon of chromothripsis, where a single chromosome or chromosome arm appears to undergo massive breakage and rearrangement.
About David Pellman
David Pellman is the Margaret M. Dyson Professor of Pediatric Oncology at the Dana-Farber Cancer Institute and the Children’s Hospital Boston. He is also Professor of Cell Biology at Harvard Medical School and an Investigator of the Howard Hughes Medical Institute. Dr. Pellman received his MD from the University of Chicago, Pritzker School of Medicine. He completed an internship and residency at Dana-Farber Cancer Institute and Children's Hospital Boston. He was a postdoctoral fellow at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology.
He has received numerous awards including: the Graduate Student Mentoring Award from Harvard Medical School (1999), the Stohlman Scholar Award from the Leukemia & Lymphoma Society (2005); and the E. Mead Johnson Award from the Society for Pediatric Research (2006).