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Exploring the role of UCHL1 in leukemia and lymphoma
Cellular proteins must occasionally be destroyed in order to maintain the proper functioning of the cell. This is especially true of cancer cells where the destruction of proteins that halt cell division is required for the continued expansion of the cancer. Specific protein removal is the task of the ubiquitin-proteasome pathway. Because of the importance of protein breakdown in cell division, much attention has turned towards gaining a better understanding of the way proteins are targeted for destruction and conversely how their fates are spared. Dr. Galardy’s lab has identified an enzyme in the ubiquitin-proteasome pathway that is highly expressed in most common forms of leukemia and lymphoma. This enzyme, called UCHL1, promotes the development of these cancers through mechanisms that are still unclear. More importantly, it is also unknown whether an inhibitor of UCHL1 could effectively prevent lymphoma from developing, or kill cancers that have already developed. In this proposal Dr. Galardy and his lab seek to answer these questions using novel mouse models so that they can establish the feasibility of targeting UCHL1 in these aggressive cancers.