A Powerful Pathway: Part One
What if you could make some genes better protect cells against environmental carcinogens and toxins? Toxicologists Thomas Kensler, John Groopman and colleagues began with this premise a quarter-century ago and soon concentrated on one cellular pathway, Keap1-Nrf2-ARE. The Keap1 protein is anchored onto the cell's cytoskeleton, where, like some mythic beast, it continually consumes another protein, Nrf2. But in certain circumstances, Keap1 releases Nrf2, which then heads straight to the cell's nucleus and to docking sites called AREs in the DNA sequences of different chromosomes. Nrf2's arrival causes genes containing ARE to produce carcinogen-fighting enzymes. Using this pathway, the team has sought to prevent liver cancer in parts of China where it is epidemic. They've found that new drugs and compounds in foods like broccoli prime this pathway. A clinical trial using tea made from broccoli sprouts has yielded encouraging results in protecting people against environmental carcinogens.
A Powerful Pathway: Part Two
In cell biology, a signaling cascade occurs when one protein activates another protein, which in turn triggers another, and so on to perform a task. Research works the same way. One scientist's discovery sparks another's mission. Thomas Kensler and colleagues have demonstrated Nrf2's promise in preventing liver cancer (previous story). Now pulmonary toxicologist Shyam Biswal has taken the Nrf2 ball and run with it. In 2001, Nrf2 was known to regulate the expression of less than a dozen genes. With new technology, Biswal discovered that Nrf2 regulates more than 500 genes—clearly demonstrating its broad detoxification powers. Biswal expects to show that Nrf2 plays a key role in defending the body against everything from infectious agents to allergic asthma, emphysema and Parkinson's disease. The discoveries have made the researchers optimistic: "We want to make humans as resistant as possible to challenges from environmental agents," says Kensler.
A Protein Early Warning System
Each year, millions of children die or suffer ill health and impaired development because their diets lack essential micronutrients like vitamin A, zinc, iron or iodine. But health workers do not have a practical way to identify such deficiencies. If a field-based test existed, they could quickly discover a community's nutritional needs and provide the required supplements. Enter a Bloomberg School team that includes nutritionist Keith West, toxicologist Jim Yager, biostatistician Ingo Ruczinski and molecular biologists Bob Cole (of Hopkins Medicine) and Peter Scholl. They think one solution may be to assess proteins in the bloodstream involved in the body's use of micronutrients. The team is using serum samples from pregnant women in Nepal to identify proteins that might signal several micronutrient deficiencies at the same time. The ultimate goal: Developing a method that can detect micronutrient deficiencies so they can be prevented before they lead to major public health problems.
