Philip Hanawalt (l) accepts the award from John Little of the Department of Cancer Cell Biology

Nearly 240 people attended this year’s symposium, more than ever before. The symposium, themed "Cell Signaling in Radiobiology and Carcinogenesis," drew cancer researchers, corporate scientists, and journalists.

The John B. Little Center for Radiation Sciences and Environmental Health at HSPH sponsors the symposium.

In 1964, Hanawalt and colleagues described a mechanism by which damaged nucleotides in DNA strands are excised and replaced, leaving the healthy DNA strands to be reconnected by the protein ligase. The discovery helped explain how cells maintain genetic stability and avoid cancer development.

Over the past 15 to 20 years, Hanawalt and scientists in his lab have conducted research into the subpathways of DNA repair systems. They have discovered that expressed genes are the first to be fixed if damaged and, furthermore, that some proteins involved in DNA repair are also involved in DNA transcription. These findings are important for investigations in oncology, aging, developmental biology, environmental health, and neurobiology.

The findings help scientists understand how cancer develops, especially in rare diseases such as xeroderma pigmentosa (XP) that stems from a deficiency in DNA repair. XP patients are extremely sensitive to sunlight and are at high risk for dying from cancer, especially skin cancer. Another rare disease studied by Hanawalt, Cockayne syndrome, causes sunlight sensitivity, stunts growth, impairs mental functions and increases risk of cataracts.

More than a dozen other researchers spoke at the symposium. Robert Weinberg of the Whitehead Institute for Biomedical Research described his attempts to create more realistic models of how tumors develop in human cells by exploring the interactions of different cell types.

Joan Brugge of Harvard Medical School has developed a three-dimensional cell culture model that allows the growth of in vitro breast cells in imitation of how they would organize in the body. Using the model, Brugge has uncovered indications of how a specific gene sends signals that affect breast glands during early tumor development.

Eric Wright of the University of Dundee talked about the reaction of the immune system, particularly macrophages, to ionizing radiation. Macrophages can eat dying cells, but they also cause inflammatory reactions in the body. Wright is looking at how the inflammation can lead to increased risk for cancer.

Jean Wang of the University of California, San Diego discussed how and when nascent cells are given the go-ahead to continue developing if DNA damage is detected.

Zhi-Min Yuan of HSPH described his lab’s work in obtaining evidence to demonstrate how the MDMX and MDM2 proteins are involved in regulating the tumor suppressor p53. Their findings support a model where MDMX, which is essential to enable MDM2 to maintain p53 at low levels in non-stressed cells, is down-regulated by MDM2 in stressed cells. The down-regulation results in a rapid activation of p53, which ensures an optimal response to stress and decreases the likelihood of cancer.

Tyler Jacks of the MIT Center for Cancer Research is looking into the relationship between p53 and Li-Fraumeni Syndrome, an inherited condition that predisposes people to cancer.

Michael Greenberg of Children’s Hospital Boston explored the functions of the "forkhead" gene regulators, which modulate genes required for cell survival.

David Livingston of the Dana-Farber Cancer Institute explored the role of the BRCA1 gene in breast cancer development and how it might have a normal function in controlling the activity of the X chromosome.

Martin Lavin of the Queensland Institute of Medical Research described how proteins involved in the development of ataxia telangiectasia may work with gene products of another rare disease, Bloom’s Syndrome, to elevate cancer risk.

Peter Jones of the University of Southern California explored how DNA methylation, a process by which the body controls gene expression, may turn off tumor-suppressing cells.

Richard Kolesnick of the Memorial Sloan-Kettering Cancer Center described how components of cell membranes called rafts are involved in radiation responses.

Mary Ann Stevenson of Beth Israel Deaconess Medical Center explained the role of the pkr gene in stabilizing mRNA, which transcribes genes.

For more info, visit www.hsph.harvard.edu/ccb/JBL/JBL2002/JBLV.htm.