ASCI / Emerging-Generation Awards, 2023

Jonathan Michael Tsai, MD, PhD, as a physician-scientist, seeks to continue into an independent academic career with a clinical practice in molecular pathology and research focus understanding the relationship between protein degradation and transcriptional regulation. He began his training at the California Institute of Technology in Dr. David Baltimore’s laboratory where he completed his undergraduate thesis developing a high-throughput multiplexed assay to isolate T-cell receptor genes from single tetramer sorted T-cells. Dr.Tsai spent one year on a Fulbright fellowship at the Weizmann Institute of Science in Rehovot, Israel with Dr. Yosef Yarden, studying growth receptor signaling and cell migration. He completed his medical and graduate training at Stanford University in the Dr. Irving Weissman’s laboratory, where he identified the mesothelium as the cell-of-origin of peritoneal adhesions. As a Clinical Pathology resident and Molecular Genetics Pathology fellow at Brigham and Women’s Hospital, Dr. Tsai led the development of clinical diagnostic assays, particularly a targeted next-generation sequencing lymphoma panel with clinicians at Dana-Farber Cancer Institute. For his post-doctoral work, he joined Dr. Benjamin Ebert’s laboratory where he characterized the E3 ligase UBR5 as a general regulator of nuclear hormone receptor degradation, showed that UBR5 degrades its substrates on chromatin, and surprisingly acts as a transcriptional activator. Dr. Tsai is currently focused on how UBR5 and E3 ligases use protein degradation to activate transcription. As a physician-scientist, he aims to leverage functional genomics, biochemistry, and epigenetics to understand how this affects oncogenesis by studying patient specimens in Pathology archives. Dr. Tsai's vision is to redefine how we think about transcription factor biology, as additionally regulated by protein degradation, which may lead to the consideration of E3 ligases as new actionable cancer targets.