• Researcher Profile

    David M. Livingston, MD

     
    David M. Livingston, MD
     
    Emil Frei Professor of Genetics and Medicine, Harvard Medical School

    Office phone: 617-632-3074
    Fax: 617-632-4381
    Email: david_livingston@dfci.harvard.edu

    Preferred contact method: office phone
     
     

    Research Department

    Cancer Biology

    Area of Research

    Molecular Pathogenesis of Breast and Ovarian Cancer

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Smith 870
    Boston, MA 02215

    Biography

    David Livingston is Deputy Director of the Dana-Farber/Harvard Cancer Center; Chief of the Charles A. Dana Division of Human Cancer Genetics, and the Emil Frei Professor of Genetics and Medicine at Harvard Medical School. From 1996 to 2000, he served as Chairman of the Executive Committee for Research at the Dana-Farber Cancer Institute, leading the senior faculty group that oversees all aspects of the Institute's research program. He reassumed that post in 2005 and has been in it since that time. Dr. Livingston has been a Harvard faculty member continuously since 1973.

    Dr. Livingston received an A.B. cum laude from Harvard College in 1961, an M.D., magna cum laude, from Tufts University School of Medicine in 1965, and served his internship and residency in internal medicine at the Peter Bent Brigham Hospital in Boston (now Brigham and Women's Hospital). In 1967, he became a Research Associate at the National Cancer Institute (NCI) in molecular biology and biochemistry; he continued his work as a Research Fellow in Biological Chemistry at Harvard Medical School in 1969. Dr. Livingston returned to NCI in 1971 as a Senior Staff Fellow where he began his career in cancer research. He was recruited to Dana-Farber (then the Childrens Cancer Research Foundation) in 1973.

    Dr. Livingston is an internationally recognized expert on genes that regulate cell growth in the body - genes that, when they go awry, can lead to cancer. These genes are called oncogenes and tumor suppressor genes. Through his research, Dr. Livingston has uncovered detailed biochemical steps required to initiate and maintain the transformation of these cells into tumor cells. His focus is on the regulatory controls of signal transduction - the smooth and coordinated flow of special chemical signals from the surrounding environment to the cell, where it is transduced into specific commands that tell cells whether or not to grow - and their role in cancer development. In recent years, his work has centered on those key molecular steps that trigger the development of breast and ovarian cancer.

    Dr. Livingston is the recipient of numerous awards and honors. He has been elected to the Institute of Medicine of the National Academy of Sciences, the National Academy of Sciences, itself, and the American Academy of Arts and Sciences. He sits on multiple editorial boards, the science advisory boards of other research institutions, and is a member of the Association of American Physicians, the American Society for Clinical Investigation, the American Society for Microbiology, and the American Academy of Microbiology. He is also a Foreign Associate of the European Molecular Biology Organization and serves as Vice Chair of the Board of the Damon Runyan Cancer Research Foundation. Dr. Livingston has authored more than195 scientific publications.

    Recent Awards

    • AACR-G.H.A. Clowes Award, 2005
    • Boveri Award for Molecular Cancer Genetics, German Cancer Society, 2005
    • Lila Gruber Honor Award for Cancer Research, American Academy of Dermatology, 2001
    • Member, American Academy of Arts and Sciences, 2001
    • Baxter Award for Distinguished Research in the Biomedical Sciences, AAMC, 1997

    Research

    Molecular Pathogenesis of Breast and Ovarian Cancer

    Our laboratory is dedicated to the study of processes that, when defective, allow human cells to develop malignant characteristics. These processes are, in part, controlled by tumor suppressor loci. We continue to concentrate our efforts on a subset of these loci, all of which exert their functions in the nucleus. Some participate in the control of cell proliferation, others in the control of genome integrity, and still others in mechanisms that underlie the ability of cells to thrive in low-oxygen environments and under other stresses. Based on some unexpected results, we have extended our work over the past two years to explore the events that give stem cells of certain tissues the ability to self-renew.

    A fraction of our effort is dedicated to understanding the genetics of breast and ovarian cancer development. In particular, we are studying the in vivo biochemical and biological functions of four genes - BRCA1, BRCA2, BACH1, and BARD1 - which encode large nuclear proteins that interact specifically with one another. At least three and likely all four of these proteins are products of tumor suppressing loci. Together, they function as parts of large nuclear complexes that participate in the response of cells to DNA damage, and perhaps in other basic functions as well. When BRCA1, BARD1, or BRCA2 is rendered defective by germline mutation in females, tumor development develops at higher than normal frequencies in the breast and the ovary. A major segment of our ongoing work is aimed at trying to understand how, in biochemical terms, BRCA1 and BRCA2 perform their tumor suppressing effects and why, in the case of BRCA1, these effects are detected in the cells of women but not men.


    Select Publications

    • Chan HM, Masako N, Lowe SW, Livingston DM. P400 participates in the p53/p21 senescence pathway. Genes Dev 2005;19:196-201.
    • Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, Livingston DM, Rajewsky K. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 2005;19:489-501.
    • Cantor S, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, Livingston DM. The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. Proc Natl Acad Sci U S A 2004;101:2357-62.
    • Taubert S, Frank SR, Parisi T, Fuchs M, Chan HM, Livingston DM, Amati B. E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G1. Mol Cell Biol 2004;24:4546-56.
    • Kung AL, Zabuldoff SD, France DS, Freedman SSJ, Tanner EA, Viera A, Cornell-Kennon S, Lee J, Wang B, Wang J, Memmert K, Naegeli HU, Petersen F, Eck MJ, Bair KW, Wood AW, Livingston DM. Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell 2004;6:33-43.
    • Wu X, Avni D, Chiba T, Yan F, Zhao Q, Lin Y, Heng H, Livingston DM. SV40 T antigen interacts with Nbs1 to disrupt DNA replication control. Genes Dev 2004;18:1305-16.
    • Elshamy WM, Livingston DM. Identification of BRCA1-IRIS, a BRCA1 locus product. Nat Cell Biol 2004;6:954-67.
    • Avni D, Yang H, Martelli F, Hofmann F, ElShamy W, Livingston, D. Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage. Mol Cell 2003;12:735-46.
    • Grossman SR, Deato ME, Brignone C, Chan HM, Kung A, Tagami H, Nakatani Y, Livingston DMA. Polyubiquitination of p53 by a ubiquitin ligase activity of p300. Science 2003;300:342-4.
    • Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K. Aberrant T cell differentiation in the absence of Dicer. J Exp Med 2005;202:216-69.

    Investigators

    • Joukov, Valdimir, MD, PhD
    • De Nicolo, Arcangela, MD, PhD

    Trainees

    • Sheng, Qing, PhD
    • Liu, Ben, PhD
    • Pathania, Shailja, PhD
    • McKinney, Kristine, PhD
    • Yang, Yi-Li, MD, PhD
    • Dimitrov, Stoil, MD, PhD
    • Yang, YieYie, PhD
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