Community Academic Profiles

Professional Snapshot

Administrative Appointments

  • Director, Division of Radiation and Cancer Biology (1984 - 2004)
  • Director, Graduate Program in Cancer Biology (1990 - 2002)

Honors and Awards

  • Henry S. Kaplan Distinguished Scientist Award, International Association for Radiation Research (2007)
  • Weiss Medal, Association for Radiation Research (2001)
  • Gold Medal, Americal Society for Therapeutic Radiology and Oncology (1999)
  • Bruce Cain Memorial Award, American Association for Cancer Research (1999)

Education & Community

Professional Education

  • B.Sc, Birmingham University, Physics (1963)
  • M.Sc, London University, Radiation biology and physics (1965)
  • Ph.D, Oxford University, Cancer Biology (1968)

Graduate & Fellowship Program Affiliations

Scientific Focus

Research Interests

Our goal is to understand the mechanisms responsible for the resistance of solid tumors to various cancer therapies and to develop strategies to overcome these resistances. Projects include:

1) Exploitation of tumor hypoxia: Hypoxic cells, characteristic of solid tumors, are resistant to killing by ionizing radiation and by many anticancer drugs. We have developed a drug (tirapazamine or TPZ) activated by low oxygen levels to a toxic species that is selective for solid tumors and is undergoing clinical testing both at Stanford and elsewhere. We use a variety of cellular and molecular techniques to study various aspects of the mechanism of action of TPZ. In addition we have an active program to understand the mechanism and clinical utility of a new hypoxia activated bifunctional mustard, PR-104, a drug that produces DNA interstrand crosslinks and which has entered clinical trials.

2) Identification of genes affecting cancer susceptibility and the sensitivity of cells to anticancer agents. We are using a pool of strains of budding yeast (S.cerevisiae) with single deletions of all open reading frames (ORFs). This pool allows simultaneous analysis of all genes by hybridization to a high density oligonucleotide array (Winzeler et al. Science 285:901 (1999)), thereby allowing the rapid identification of genes and pathways involved in the mechanism of action of anticancer agents and the response of the cell to the agents. This system provides a powerful new tool to identify the genes affecting the cell response to anticancer agents as well as potentially identify new tumor suppressor genes in humans.

3) Development of anaerobic bacteria as tumor specific gene therapy agents: Certain nonpathogenic Clostridial species proliferate exclusively in the hypoxic/necrotic regions of solid tumors. We have developed shuttle vectors which express an enzyme capable of activating a non-toxic prodrug into a toxic drug in those bacteria and have shown that this...

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