Many proteins are removed through a process termed ubiquitination; recent studies have used small molecules like molecular glues and PROTACs to target proteins that would not otherwise be removed. Drugs like lenalidomide have been used to treat diseases like multiple myeloma and myelodysplastic syndromes. Recently, more compounds have been developed to target a variety of cancer-causing proteins. Our group recently found that ubiquitination and protein removal play a critical role in gene expression. We are interested in studying the effects of ubiquitin and protein removal on specific proteins called transcription factors, that often drive cancers and other diseases. A better understanding of this process will uncover new vulnerabilities that can be used for cancer treatment.

Nuclear hormone receptors are a family of transcription factors that responds to small molecules like hormones. Aberrant hormone signaling drives a number of diseases, including breast and prostate cancers, two of the most common malignancies world-wide. We recently discovered that a general mechanism of hormone receptor degradation and are interested in expanding our knowledge of how hormone receptors are degraded to develop tools to treat diseases like breast and prostate cancer.

Hormones and hormone derivatives account for about 15% of all prescribed medications. While many are effective, drugs like corticosteroids have many unwanted side effects leading to issues ranging from weight gain to mood changes. Using the principles we have discovered above, we aim to screen for and design more effective hormone ligands to treat diseases like leukemia, lymphoma, and breast and prostate cancers.