• Researcher Profile

    David S. Pellman, MD

     
    David S. Pellman, MD
     
    Margaret M. Dyson Professor of Pediatric Oncology
    Professor of Cell Biology, Harvard Medical School
    Investigator, Howard Hughes Medical Institute


    Office phone: 617-632-4918
    Fax: 617-632-6845
    Email: david_pellman@dfci.harvard.edu

    Preferred contact method: email
     
     

    Research Department

    Pediatric Oncology

    Area of Research

    Cell Division and Genome Stability


    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Mayer 663
    Boston, MA 02215

    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. In 2008, he was appointed as an Investigator of the Howard Hughes Medical Institute.

    Recent Awards

    • AAAS Fellow, Medical Sciences, 2012
    • Association of American Physicians, 2010
    • American Pediatric Society (APS), 2008
    • HHMI, Investigator, 2008
    • E. Mead Johnson Award, Society of Pediatric Research, 2006
    • 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, 1996
    • Claudia Adams Barr Investigator, DFCI, 1994
    • NIH Clinical Investigator Award, 1992
    • St. Jude's Children's Hospital Fellow in the Pediatric Scientist Training Program, 1989
    • Alpha Omega Alpha Research Fellowship, 1986
    • Catherine Dobson Prize for Research; University of Chicago, Pritzker School of Medicine, 1986

    Research

    Cell Division and Genome Stability

    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 chomosome 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.  

    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.
    • Ganem N, Godinho S, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature 2009; 460: 278-82. PMID: 19506557
    • 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. PMID: 21884976
    • Gordon DJ, Resio B, Pellman D. Causes and consequences of aneuploidy in cancer. Nature Review Genetics 2012; 3:189-203. PMID: 22269907
    • 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(7383): 53-8.  PMID: 22258507

    Trainees

    • Kwon, Mijung, PhD
    • Selmecki, Anna, PhD
    • Gordon, David, MD, PhD
    • Chiu, Shang-Yi, PhD
    • Cornils, Hauke, PhD
    • Stokasimov, Ema, PhD
    • Picone, Remigio, PhD
    • Varetti, Gianluca, PhD
    • Kaplan-Dor, Yosef, PhD
    • Spector, Alex, MD, PhD