David Pellman

Department of Pediatric Hematology and Oncology
Dana Farber Cancer Institute

Howard Hughes Medical Institute
44 Binney Street, Mayer 663
Boston, MA 02115
Tel: (617) 632-4918
Fax: (617) 632-6845
Email: David_Pellman@dfci.harvard.edu

Web Page: The Pellman Lab Page
9 postdoctoral fellows, 3 graduate students

Our laboratory works on cell biology topics in two interrelated areas: cytoskeletal regulation and the control of genome stability. We take a range of approaches including genetics, functional genomics, biochemistry and live cell imaging. There are ongoing projects using yeast, mammalian tissue culture, 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. For example, we have recently uncovered a mechanism by which actin organization and the adhesive microenvironment of cells influence chromosome segregation. We have defined cytoskeletal mechanisms that control polarized cell growth and asymmetric cell division. We use biochemical and imaging approaches to understand these processes at a mechanistic level as well as to understand how these events are properly timed during the cell cycle.

We are also interested in how aneuploidy (abnormal chomosome number) and polyoidy (increased sets of chromosomes) impact on tumor biology. We recently found that failure of cytokinesis, which doubles the number of chromosomes and centrosomes, promotes tumorigenesis in a mouse breast cancer model. We are studying the consequences of having extra centrosomes in cancer cells. Finally, we are taking various approaches to understand the consequences of having extra chromosomes (aneuploidy) in cells. For example, we are using yeast to ask whether aneuploidy or polyploidy can affect the rate of adaptation (evolution).

References:

Fujiwara, T., Bandi, M., Nitta, M., Ivanova, E. V., Bronson, R. T., and , Pellman D. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-/- cells. Nature, 2005, 437: 1043-7.
Yoshida S, Kono K, Lowery DM, Bartolini S, Yaffe MB, Ohya Y, Pellman D. Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis. Science 2006;313:108-11.
Storchova Z, Breneman A, Cande J, Dunn J, Burbank K, O'Toole E, Pellman D. Genome-wide genetic analysis of polyploidy in yeast. Nature 2006;443:541-7.
Kwon,M, Godinho, SA, Chandhok, NS, Ganem, NJ, Azioune, A, Thery, M, and Pellman, D. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes & Development 2008, In Press.