Department of Pediatric Hematology and Oncology
Howard Hughes Medical Institute
450 Brookline Ave., Mayer 663
Boston, MA 02115
Lab Members: 9 postdoctoral fellows, 4 graduate students
Visit my lab page here.
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 have recently defined how these cytoskeletal elements are reorganized after cellular membrane wounds. We use biochemical and imaging approaches to understand these processes at a mechanistic level.
We are also interested in how aneuploidy (abnormal chomosome number) and polyploidy (increased sets of chromosomes) impact tumor biology and evolution. 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. We have developed methods to evolve cancer relevant phenotypes in the laboratory, enabling a dissection of the underlying mechanisms.
Ganem N, Godinho S, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature 2009; 460: 278-82.
Su X, Qui W, Gupta M, Pereira-Leal J, Reck-Peterson S, Pellman D. Mechanism underlying the dual-mode regulation of microtubule dynamics by Kip/3kinesin-8. Mol Cell 2011; 3: 751-63.
Gordon DJ, Resio B, Pellman D. Causes and consequences of aneuploidy in cancer. Nature Review Genetics 2012; 13;189-203.
Crasta K, Ganem N, Dagher R, Lantermann A, Ivanova E, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D. Mitotic chromosome segregation errors cause DNA breaks and chromosome pulverization. Nature 2012; 482:53-8.
Kono K, Saeki Y, Yoshida S, Tanaka K, Pellman D. Proteasomal Degradation Resolves Competition between Cell Polarization and Cellular Wound Healing. Cell 2012; 150:151-64.
For a complete listing of publications click here.
Last Update: 7/26/2012