David Steven Pellman
Our laboratory aims to understand normal cell division mechanisms and to discover cell division defects that are unique to cancer cells. 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 have a long-standing interest in spindle orientation, centrosome position, and asymmetric cell division. We discovered mechanisms that link microtubules to polarized actin in yeast, and have recently defined analogous mechanisms in human cells. 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 use biochemical and imaging approaches to understand these processes at a mechanistic level.
We are also interested in how aneuploidy (abnormal chromosome number) impacts tumor biology. We are particularly interested in the consequences of whole genome duplications, which recent genomic data suggest occur in nearly 40% of human cancers. We previously found that whole genome duplications resulting from cytokinesis failure can drive tumor development. We recently identified a mechanism by which errors in the segregation of intact chromosomes can cause DNA breaks, potentially resulting in cancer-causing mutations. 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 are using single cell genome sequencing to define the impact of cell division errors on genome architecture.
Howard Hughes Medical Institute
450 Brookline Ave., Mayer 612
Boston, MA 02215