Marc Ostermeier: Flipping the Switch on Cancer

Marc Ostermeier in the lab
Marc Ostermeier and doctoral student Clay Wright work together in Ostermeier's lab. (Photo by Will Kirk)

 

Discover Magazine, "Top 100 Stories of 2011" Targeted cancer therapies are a kind of biological manhunt: they find and kill cancer cells while leaving healthy cells alone, thus lessening the unpleasant and often dangerous side effects of cancer treatment. A research team led by Marc Ostermeier is turning this mission inside out. They are developing a new way to cause cancer cells to kill themselves—from within. Their work, which appeared last year in Proceedings of the National Academy of Sciences, was cited in Discover Magazine’s “Top 100 Stories of 2011.”

Ostermeier, professor and vice chair of ChemBE, has created a protein “switch” that ignites a cell-killing drug in cells with high levels of a cancer biomarker known as HIF-1α. The switch is made up of two proteins: one that detects HIF-1α and another that activates the drug. Here’s how it works: An inactive form of the drug, called a “prodrug,” is administered to all cells, but only when the protein switch inside the cell comes into contact with the biomarker does it change the prodrug into an active, lethal weapon. “The switch senses, this is a cancer cell, and decides to convert the prodrug to a drug,” says Ostermeier. Ideally, the prodrug remains unactivated in healthy cells.

Ostermeier and his colleagues have tested the switch successfully in human cell cultures and are currently testing the switch in mice. Meanwhile, though the switch may already be of therapeutic benefit, they continue to try to perfect it. “It isn’t completely off when we want it be and isn’t completely on when we want it to be,” says Ostermeier. “And the better it does that, the more effective it’s going to be.”

- Kristi Birch

In a study published in PNAS, the Ostermeier Lab developed a protein “switch” that induces cell-death in cancer cells with high levels of HIF-1α.