Tom Curran, Ph.D., FRS

  • Department: Pathology
  • Division: Transplantation Immunology
  • Email: currant@email.chop.edu
  • Primary Address:
    CHOP - Colket Translational Research Building
    Room 4060
    3501 Civic Center Boulevard
    Philadelphia, PA 19104
  • 267-426-2819

    Expertise

    ITMAT:

    The Curran laboratory studies brain development and pediatric brain tumors. The goal is to identify molecular changes and potential drug targets. Additional studies focus on the mechanism of action of anticancer drugs in tumor cells and cancer models.

    RESEARCH:

    Research Interests
    Brain tumors, brain development, genomics.
    Key words: Brain, Development, Molecular Oncology, Reelin, sonic hedgehog, neuro-oncology, oncogenes

    Description of Research
    Our research addresses the molecular basis of normal and neoplastic growth in the developing nervous system. We hope that by understanding the normal processes that govern formation of the brain we will uncover new approaches for the treatment of rare but very devastating pediatric brain tumors. Research in the laboratory combines basic approaches with genomics and translational science in a broad-based effort. Our experimental strategies include mouse disease models, cell culture, genomics, human tumor samples, imaging and a range of molecular techniques.

    Previously, we identified the reelin gene (Reln) whose protein product is a large extracellular protein that controls cell migration and is secreted by several early populations of neurons in the developing brain. We are now examining the molecular events downstream of Reln that mediate its function. To accomplish this we are developing several conditional mutant mouse lines and we are utilizing cell and molecular biology approaches.

    We are taking genomic approaches to identify molecular changes and potential drug targets for several brain tumors including medulloblastoma, atypical teratoid/rhabdoid tumors and choroid plexus carcinomas. We developed a model system with a 100 percent incidence of spontaneous medulloblastoma for use in translational studies. Recently, we found that a small molecule inhibitor of the sonic hedgehog (Shh) pathway eliminated even large tumor masses in vivo. We are continuing to analyze the mechanism of action of several anticancer drugs in tumor cells and cancer models.

    Rotation Projects
    Opportunities are available to investigate the response of brain tumors to molecular targeted therapies in genetic mouse models. Opportunities are also available to investigate the molecular control of cell migration in the developing brain and signaling components of the Reelin pathway. Please contact Dr. Curran for available projects.

    Lab personnel:
    Jessica Ng, Ph.D. Tae-Ju Park, Ph.D., Jillian Brechbiel, Ph.D., Mariel Boyd, Technician; Benjamin Sawtzky, Technician; Dianne Settles, Resource Coordinator

    Appointments

    Professor of Cell and Developmental Biology, University of Pennsylvania School of Medicine (2008 – present)
    Professor of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine (2006 – present)

    Education

    PhD, Zoology and Anatomy, Imperial Cancer Research Fund Laboratories and University College London (1982)
    BSc (Hons), Zoology, University of Edinburgh (1978)

    Selected Publications

    Park, TJ, Curran, T. Crk and Crk-Like Play Essential Overlapping Roles Downstream of Disabled-1 in the Reelin Pathway. Journal Of Neuroscience. Vol 28(50) . 2008 DEC 10:13551-13562.
    Kimura H, Ng JMY, Curran T.. Transient inhibition of the Hedgehog pathway in young mice causes permanent defects in bone structure.. Cancer Cell. Vol 13. 2008:249-60.
    Curran Tom, Ng Jessica M Y. Cancer: Hedgehog's other great trick.. Nature. Vol 455(7211) . 2008 Sep:293-4.
    Park TJ, Boyd K, Curran T. Cardiovascular and craniofacial defects in Crk-null mice. Mol Cell Biol. Vol 26(16) . 2006:6272-82.
    Sasai K, Romer JT, Lee Y, Finkelstein D, Fuller C, McKinnon PJ, Curran T. Shh pathway activity is down-regulated in cultured medulloblastoma cells: implications for preclinical studies. Cancer Res.. Vol 66(8) . 2006:4215-22.
    Romer JT., Kimura H., Magdaleno S., Sasai K., Fuller C., Baines H., Connelly M., Stewart CF., Gould S., Rubin LL., Curran T.. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice.[see comment]. Cancer Cell. Vol 6(3) . 2004 Sep:229-40.
    D'Arcangelo G., Miao GG., Chen SC., Soares HD., Morgan JI., Curran T.. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler.[see comment]. Nature. Vol 374(6524) . 1995 Apr 20:719-23.
    Abate C., Patel L., Rauscher FJ 3rd., Curran T.. Redox regulation of fos and jun DNA-binding activity in vitro. Science. Vol 249(4973) . 1990 Sep 7:1157-61.
    Gentz R., Rauscher FJ 3rd., Abate C., Curran T.. Parallel association of Fos and Jun leucine zippers juxtaposes DNA binding domains. Science. Vol 243(4899) . 1989 Mar 31:1695-9.
    Morgan JI., Cohen DR., Hempstead JL., Curran T.. Mapping patterns of c-fos expression in the central nervous system after seizure. Science. Vol 237(4811) . 1987 Jul 10:192-7.