# Jonathan Tsai Assistant Professor of Pathology ![Tsai](/sites/g/files/omnuum5321/files/styles/hwp_4_5__480x600/public/2025-06/Tsai%20Photo.jpg?itok=mZLehhjy) email laptop\_windows [Lab Website](https://tsailab.bwh.harvard.edu/) laptop\_windows [Publications](https://www.ncbi.nlm.nih.gov/myncbi/1vU9ycyDmxa5j/bibliography/public/) Brigham and Women's Hospital 221 Longwood Avenue, Room 401A Boston, MA 02115 The Tsai Laboratory studies transcription factor protein stability and developing new methods to target transcription factors for degradation to treat disease. Many proteins are removed through ubiquitination and proteasomal degradation; recent studies have used small molecules like molecular glues and PROTACs to target previously undruggable proteins for degradation. 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 broadly interested in studying the effects of ubiquitin and protein removal on transcription factors, and how that regulates gene expression. We have a specific interest in nuclear hormone receptors, a family of transcription factors that responds to small molecules like hormones, including the estrogen and androgen receptors. Aberrant hormone signaling drives a number of diseases, including breast and prostate cancers, two of the most common malignancies world-wide. We recently discovered two pathways of hormone receptor degradation. The first is a general, conserved mechanism that is responsible for the native recycling of hormone receptors on chromatin. The second is a small molecule induced, alternate pathway that leads to increased antagonism and has been successfully used to treat metastatic breast cancer. We are interested in expanding our knowledge of how hormone receptors are degraded to develop tools to treat hormone driven diseases like breast and prostate cancer. Finally, 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 understand the structure-function relationships these hormone and hormone derivatives induce in their receptors, and screen for and design more effective and precise hormone ligands to treat diseases like leukemia, lymphoma, and breast and prostate cancers. - ## Program Affiliation [Biological Chemistry and Molecular Pharmacology](/bbs-faculty/biological-chemistry-and-molecular-pharmacology) - ## Discipline [Cell Biology](/discipline/cell-biology) [Genetics](/discipline/genetics) [Genomics](/discipline/genomics) [Molecular Biology](/discipline/molecular-biology) [Pharmacology](/discipline/pharmacology) [Synthetic & Systems Biology](/discipline/synthetic-systems-biology) - ## Organism [Human](/organism/human) [Mouse](/organism/mouse) - ## People [Faculty](/people/faculty) - ## Location [Brigham and Women's Hospital](/location/brigham-and-womens-hospital)