Research Department

Pediatric Oncology

Area of Research

Biography

Dr. Pellman received his MD in 1986 from the University of Chicago, Pritzker School of Medicine, and did postgraduate training in pediatrics and pediatric hematology-oncology at DFCI and Children's Hospital, Boston. He was a postdoctoral fellow at the Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology. In 1995, he joined DFCI, and is currently the Margaret M. Dyson Professor of Pediatric Oncology, Professor of Cell Biology, Harvard Medical School

Recent Awards

• Stohlman Scholar, Leukemia and Lymphoma Society, 2005
• American Society for Clinical Investigation, 2001
• BASF Bioresearch Award, DFCI, 2001
• Scholar Award, Leukemia & Lymphoma Society, 2000
• Graduate Student Mentoring Award, Harvard Medical School, 1999
• Kimmel Scholar Award, 1998
• Damon Runyon Scholar Award, 1997

Research

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, 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 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 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 defining the consequences of having extra centrosomes in cancer cells. We are using yeast to ask whether aneuploidy or polyploidy can affect the rate of adaptation (evolution). We have developed methods to generate human cells with specific cancer-associated trisomies.

Select Publications

• Mosley JB, Sagot I, Manning AL, Xu Y, Eck MJ, Pellman D, Goode BL. A conserved mechanism for Bni1- and mDia-induced actin assembly and dual regulation of Bni1 by Bud6 and profilin. Mol Biol Cell 2004;15:896-907.
  
• Carvalho P, Gupta M, Pellman D. Cell cycle control of kinesin-mediated transport of Bik1 (CLIP-170) regulates microtubule stability and dynein activation. Dev Cell 2004;6:815-29.
• Sheeman B, Carvalho P, Sagot I, Geiser J, Kho D, Hoyt MA, Pellman D. Determinants of S. cerevisiae dynein microtubule plus end localization and activation: implications for the mechanism of spindle positioning. Curr Biol 2003;13:364-72.
• Schuyler SC, Liu JY, Pellman D. The molecular function of Ase1p: evidence for a MAP-dependent midizone-specific spindle matrix. J Cell Biol 2003;160:517-28.
• Storchova Z, Pellman D. Polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol 2004;5:45-54.
• Xu Y, Moseley JB, Sagot I, Poy F, Pellman D, Goode BL, Eck M. Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture.
  Cell 2004;116:711-23.
  
• Carvalho P, Tirnauer J, Pellman D. Surfing on microtubule ends. Trends Cell Biol 2003;13:229-37.
• Chestukin A, Pfeffer C, Milligan S, DeCaprio JA, Pellman D. Processing, localization, and requirement of human separase for normal anaphase progression. Proc Natl Acad Sci U S A 2003;100:4574-9.
  
• Molk JN, Schuyler SC, Liu JY, Evans JG, Salmon ED, Pellman D, Bloom K. The differential roles of budding yeast Tem1p, Cdc15p, and Bub2p protein dynamics in mitotic exit. Mol Biol Cell 2004;15:1519-32.
• Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 2005;437:1043-7.
  

Trainees

• Buttery, Shawnna, PhD
• Godinho, Susana, PhD
• Kono, Keiko, PhD
• Kwon, Mijung, PhD
• Yoshida, Satoshi, PhD
• Chiu, Shang-Yi, PhD
• Crasta, Karen, PhD
• Kuroda, Taruho, PhD
• Nezi, Luigi, PhD
• Selmecki, Anna, PhD