• Researcher Profile

    Massimo F. Loda, MD

     
    Massimo F. Loda, MD
     
    Director, Center for Molecular Oncologic Pathology

    Professor of Pathology, Harvard Medical School

    Center/Program

    Genitourinary Oncology

    Office phone: 617-632-4001
    Fax: 617-632-4005
    Email: massimo_loda@dfci.harvard.edu

    Preferred contact method: email

    View Physician Profile
     
     

    Research Department

    Medical Oncology/Molecular and Cellular

    Interests

    Urologic pathology, Molecular pathology

    Area of Research

    Lipid Metabolism and Cell Cycle Regulation in Cancer

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana 1536
    Boston, MA 02215

    Biography

    Dr. Loda received his MD in 1980 from the University of Milan, Italy, and his training in pathology at New England Deaconess Hospital. Following six years as a staff pathologist and researcher at Beth Israel Deaconess Medical Center, he joined DFCI in 1998, and currently directs the Center for Molecular Oncologic Pathology. He established and was the scientific director of the In Situ Hybridization and the Human Prostate Cancer Core Facilities at the Dana Farber/Harvard Cancer Center. He is also a senior pathologist at Brigham and Women's Hospital.

    Recent Awards

    • The Daland Award, New England Cancer Society, 1998

    Research

    Lipid Metabolism and Cell Cycle Regulation in Cancer

    While the selective and irreversible destruction of a given protein occurs through its ubiquitination, this enzymatic process can be reversed by deubiquitinating enzymes. We have been interested for several years in this family of enzymes and recently discovered that one in particular, USP2a, is androgen responsive, is overexpressed in prostate tumors, and most importantly, regulates the stability of fatty acid synthase (FAS), essential for tumor cell survival. Since inhibition of the USP2a enzyme as well as its substrate FAS results in significant prostate cancer cell death, these are important therapeutic targets in this disease. Our laboratory focuses on the role that these proteins play in prostate carcinogenesis, and in the development of USP2a and FAS inhibitors that may be used in the clinic.

    The regulation of replication in human cells is complex. Several genes are involved, either favoring or inhibiting progression of cellular division. Targeted protein degradation by the ubiquitin-proteasome pathway plays a vital role in monitoring the abundance of several proteins involved in cell cycle regulation. We have shown that loss of p27, a powerful inhibitor of cyclin-dependent kinases, has been associated with aggressive behavior in a variety of tumors including prostate cancer. Our laboratory has also demonstrated, for the first time, that targeted destruction of p27 is a mechanism used by cancer cells to become more aggressive. Furthermore, we have shown that the ubiquitin ligase responsible for the degradation of p27, Skp2, is overexpressed in estrogen receptor-negative human breast cancers. Therefore, we focus our research efforts on the dysregulation of p27 in cancer, using cell lines and animal models as well as human tumors.

    Select Publications

    • Lechpammer M, Xu X, Ellis FH, Bhattacharaya N, Shapiro GI, Loda M. Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice. Oncogene 2005;24:1683-8.
    • Signoretti S, Pires MM, Lindauer M, Horner JW, Grisanzio C, Dhar S, Majumder P, McKeon F, Kantoff PW, Sellers WR, Loda M. p63 regulates commitment to the prostate cell lineage. Proc Natl Acad Sci U S A 2005;102:11355-60.
    • Graner E, Tang D, Rossi S, Baron A, Migita T, Weinstein LJ, Lechpammer M, Huesken D, Zimmermann J, Signoretti S, Loda M. The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell 2004;5:253-61.
    • Baron A, Migita T, Tang D, Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer?
      J Cell Biochem 2004;91:47-53.

    Investigators

    • Sicinska, Ewa, MD

    Trainees

    • Priolo, Carmen, MD
    • Finn, Stephen, MD, PhD
    • Lis, Rosina, MD
    • Liu, Zhiqian, PhD
    • Mueller, Elke, MD
    • Palescandolo, Emanuele, PhD
    • Ruiz, Stacey, PhD