A growing number of oncoproteins (proteins that promote tumor growth) and pro-metastatic proteins (proteins that promote the spread of tumor cells from the original tumor site/organ) have been extensively characterized. However, many of these cancer-promoting proteins have not themselves been targeted for development of new drugs. There is a need, therefore, for alternative therapeutic strategies directed toward cancer-promoting proteins. Much attention has been paid to a small protein called ubiquitin, which is found in almost all tissues and serves as a tag that helps signal to cells how to regulate other proteins. Enzymes called deubiquitinating enzymes, or DUBs, remove ubiquitin from proteins, thereby modifying function. The hypothesis in this research is that DUBs substantially regulate key cancer proteins and pathways, thereby promoting tumor cell growth and metastases. Although DUBs have not previously been considered as good candidates for drug development, Ma hypothesizes that some types of ubiquitins can be targeted to treat cancer. In humans there are 79 DUBs, providing a wealth of possible drug targets. Researchers are working to identify and target DUBs so as to inactivate some key oncoproteins or pro-metastatic proteins, either by destabilizing them or by changing their activity. Ma’s laboratory has already identified the first DUB that suppresses tumors by regulating the key anticancer protein, PTEN. In this study, Ma is screening a library of DUBs for those that regulate key oncoproteins and pro-metastatic proteins. In parallel, she will determine which DUBs promote tumorigenesis, metastasis, or therapy resistance. The identified cancer-promoting DUBs will be tested for their ability to serve as anticancer targets, paving the way for development of DUB inhibitors as new cancer drugs.