Aaron Ciechanover, PhD, Distinguished Professor, RTICC Co-Director

Our group is part of the Rappaport Cancer Research Center, and we work in tight collaboration with many of its researchers. Our studies focus on the role of the ubiquitin system (that was discovered in our laboratory and culminated with the awarding of the 2004 Nobel Prize in Chemistry) in basic mechanisms of diseases, cancer and neurodegeneration in particular.

Our research is a nice and elegant example of how the answer to one question leads to the next, which is rather unexpected. Further, it is an example of how curiosity-driven basic research leads – by different groups – to its translation to efficient drugs to combat severe human diseases.

One area of studies in our laboratory is the mechanism by which the ubiquitin system activates NF-κB, a major transcription factor that is upregulated in many tumors and is thought to sustain, though not to initiate the malignant process. We are now studying the tumor suppressive mechanism, and it appears that it is the recruitment of the immune system which plays an important role in this process. We are developing small molecules that may mimic the process with the hope that their application can also lead to tumor suppression.

Another subject which has attracted our attention and in which we invest significant efforts is the fate of the ubiquitin system components themselves, whether and how the predator becomes a prey. Their level clearly affects their activity, which in turn affects the processes they control.

In an independent line of research we are studying the involvement of the ubiquitin system in neurodegenerative disorders – the hallmark of which is accumulation in the brain of abnormal/mutated and typically aggregated proteins. Out of several diseases, we decided to study Huntington’s disease where several good experimental tools – probes, cells, and animal models – are available.