Research Milestones
The work of every one of our faculty has important implications for our understanding of the molecular basis of disease. Two of our colleagues (Pat Brown and Gilbert Chu) made important contributions this year in the cancer area, with important implications for diagnosis and treatment. Their work is highlighted here.
By systematically comparing the gene expression patterns in diverse human carcinomas with the gene expression program observed in cultured cells responding to serum, Pat Brown found that a molecular signature related to the physiological response to a wound is a very powerful predictor of progression and metastasis in many cancers. This result has important implications for understanding the pathogenesis of cancer and suggests a possible new approach to treatment. Last year he also published results of systematic studies of gene expression programs in prostate cancer, gastric cancer, ovarian cancer and sarcomas. The results provide a potential basis for new approaches for early detection, diagnosis and individualized treatment of these cancers.
Gil Chu and colleagues have identified a way to predict whether radiation therapy will be toxic to cancer patients. Using microarray technology, he measured variations in RNA levels in response to ionizing and ultraviolet radiation. Transcriptional responses in 24 genes predicted radiation toxicity in 9 of the patients, and significantly, no false positives were found in 43 controls. In addition, no single gene cluster predicted radiation toxicity; instead, several clusters with different responses in different patients were involved, suggesting that toxicity stems from several causes. Of the 5 patients who suffered radiation toxicity but had normal transcriptional responses, 2 were treated with unconventional radiation protocols that were subsequently determined to be highly toxic. These results may eventually lead to tests that will enable physicians to predict toxicity and tailor treatment for individual patients.
Arthur Kornberg, Nobel laureate, discovered the enzymes responsible for DNA replication, and Paul Berg (Nobel laureate), Dale Kaiser, David Hogness and Ron Davis were pioneers in the field of recombinant DNA technology. More recently, Ron Davis and coworkers made major contributions to the elucidation of the sequence of the human genome. Pat Brown invented the DNA microarray, which will transform molecular diagnosis and treatment of many human diseases, especially cancer. In addition, Pehr Harbury has invented a new combinatorial chemistry and selection approach that can be applied to generation of important new drugs.
