"Tissue transplantation is fantastic but it would be so much better if we could instead raise organs from a patient's own cells," says lead investigator Raphael Kopan, Ph.D., associate professor of medicine and of molecular biology and pharmacology at Washington University School of Medicine in St. Louis. "Before we can actually trick cells into doing what we want them to do we really need to understand every detail about how the organ is put together."
Using an antibody that specifically identifies the active form of Notch, Kopan's group observed that the protein is extremely active in the kidney at an earlier stage than previously thought. So they teamed up with kidney development expert Jeffrey H. Miner, Ph.D., associate professor of medicine and of cell biology and physiology, to investigate further. First, though, they had to resolve a methodological conundrum: How do you study the effect of Notch in the kidney if animals without Notch die before the kidney begins to form?
The answer came from an entirely different field: Alzheimer's disease. In 2001, Kopan's team discovered that a group of potential Alzheimer's drugs that inhibit a protein complex called gamma-secretase also interfere with Notch. For clinical purposes, the drugs have since been refined to minimize their potentially dangerous effects on Notch. But drugs that severely inhibit this protein are perfect for studying its activity in laboratory animals.
"We took advantage of developments in different fields to allow us to do this analysis," says
Contact: Gila Z. Reckess
Washington University School of Medicine