Aaron Ciechanover, MD, DSc

About the Investigator:

Prof. Aaron Ciechanover is a Distinguished Research Professor in the Faculty of Medicine at the Technion – Israel Institute of Technology. He won the Nobel Prize in Chemistry in 2004 (along with Profs. Avram Hershko and the late Irwin Rose) for the discovery of the Ubiquitin System, the body’s method of removing damaged proteins. Based on their discovery, the anticancer drug Velcade® was developed and became the first in a class of drugs called proteasome inhibitors to be approved by the FDA for use in treating the blood cancers multiple myeloma and mantle cell lymphoma.

About the Research:

The ubiquitin system, discovered by Prof. Ciechanover and his colleagues, degrades damaged or unnecessary cellular proteins, recycling their building blocks—amino acids—to create new proteins. In rapidly dividing cancer cells, this system helps the cells survive nutrient shortages by breaking down less-essential proteins to provide amino acids for more crucial ones.

The Ciechanover lab devised a method to trick cancer cells by providing them with an excess of certain amino acids, mimicking a nutrient-rich environment. This essentially tells the cancer cells that they are not hungry, causing them to lock the ubiquitin system in the cell nucleus instead of the cytosol (the cell’s main compartment where most proteins are located). Experiments showed that enriching the environment of tumor models in mice with these amino acids caused the tumors to shrink significantly. Additionally, the lab found a link between drug resistance and the location of the ubiquitin system. In drug-resistant cells, the system is spread in the cytosol, whereas in drug-sensitive cells, it is locked in the nucleus. Adding the “tricky” amino acids moved the system into the nucleus of resistant cells, killing them and overcoming the resistance.

The main goal of this project is to understand the mechanisms behind these observations and to identify new cellular targets for future drug development.