Few things about growing older are as inevitable and obvious as “going gray,” yet scientists have been unable to explain the precise cause of this usually unwelcome transformation. In a report posted today on the Web site of the journal Science, researchers from Dana-Farber Cancer Institute and Children’s Hospital Boston say they have found the cellular cause of graying hair while investigating the origins of malignant melanoma, the potentially deadly skin cancer.

New research by investigators at Duke University Medical Center has provided insight into a fundamental cellular control mechanism that governs tissue regeneration, stem cell renewal and cancer growth. In humans, malfunctions in the pathway have been implicated in skin and brain cancers, as well as certain developmental defects, according to the researchers. The team found that the protein beta-arrestin2, earlier linked to a variety of inhibitory functions, also plays a critical role in activating the so-called hedgehog (Hh) signaling pathway, which plays a central role in early development and normal cell proliferation. When left unchecked, uncontrolled cell growth spurred by the hedgehog pathway can lead to the development of cancerous tumors. The researchers report their findings in the Dec. 24, 2004, issue of Science. The work was funded by the National Institutes of Health.

When prostate cancer, one of the leading causes of cancer death among men, spreads in the body, it most often goes to the bone where it is particularly difficult to treat. Metastasis to the bone is implicated in over 70% of prostate cancer deaths. Prof. Zelig Eshhar, Head of the Immunology Department at the Weizmann Institute of Science, has now shown how a treatment that works on cancer in the prostate can be redirected to the bones.

Researchers at Dana-Farber Cancer Institute have compiled the first atlas showing the locations of crucial gene regulators, or switches that determine how different parts of the brain develop – and, in some cases, develop abnormally or malfunction. The scientists say the map will accelerate research on brain tumors and neurological diseases that result from mutations in these switch genes – called “transcription factors.” When these genes are altered, the genes they control can go awry, causing abnormalities in the development or function of nerves and related structures. Although the gene regulators were pinpointed using mouse brains, the map applies to the human brain as well.

Scientists at the University of Michigan's Comprehensive Cancer Center and the National Cancer Institute have identified genes that promote the growth and recurrence of skin cancer. Andrzej Dlugosz, M.D., a professor of dermatology in the U-M Medical School, and colleagues at the University of Michigan and the National Cancer Institute examined the functions of the Hedgehog (Hh) signaling pathway in basal cell carcinoma – the most common form of cancer – and uncovered a subset of tumor cells that were resistant to inhibition of the Hedgehog pathway. The new finding has important implications for the treatment of this widespread disease. Their report will be published in the Jan. 15 issue of Genes & Development, but is available now on the journal's Web site.

Scientists at St. Jude Children's Research Hospital have discovered that the shape of a protein on the surface of pneumonia bacteria helps these germs invade the human bloodstream. This finding, published Dec. 16 online by the EMBO Journal, could help scientists develop a vaccine that is significantly more effective at protecting children against the disease. The St. Jude researchers determined the shape of a large, paddle-like molecule that Streptococcus pneumoniae bacteria use to latch onto cells lining the throat and lungs. The protein, called CbpA, binds to a molecule on the cell called pIgR, which takes antibodies from the bloodstream on one side of the cell and transports them to the other side. There it releases the antibody at the lining of the throat and lungs. If a pneumococcus bacterium is hovering on the lining of the respiratory tract, this germ binds to pIgR and pushes this antibody shuttle back through the cell to the bloodstream. Once at the other side of the cell, the pneumococcus breaks free of pIgR and enters the blood, where it can multiply and infect the body.