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Nicholas Brown, PhD for Pharmacology’s Seminar Series
September 26, 2023 @ 4:00 pm - 5:00 pm
For today’s pharmacology seminar we are pleased to host one of our own, Dr. Nick Brown, in recognition of his recent promotion to Associate Professor of Pharmacology, with tenure. The title of his presentation is “Mechanisms of polyubiquitination by the Anaphase-Promoting Complex/Cyclosome”
As a postdoctoral fellow with HHMI Investigator Brenda Schulman, Nick was the driver of a major project to investigate the master regulator of the cell cycle, a ubiquitin ligase known as the Anaphase-Promoting Complex (APC). He reconstituted the components of this 1.2 MDa enzyme, composed of 19 polypeptides, in a form suitable for structural studies by cryo-EM. By capturing the APC in the act of ubiquitinating and polyubiquitinating its substrate, the first for any RING E3 ubiquitin ligase, Nick has transformed our understanding of how this enzyme targets its substrates for degradation, and by extension how the cell progresses through anaphase. After being recruited to UNC in 2017, Nick and his lab have continued a remarkable level of productivity and innovation, establishing new roles for the APC in chromatin regulation (PLoS Biology 2020) and cell cycle transitions (Protein Science 2022). Recently, his group has pioneered new ways to monitor the structural transitions of the protein using mass photometry (Nature Communications 2020; Nature Structural and Molecular Biology 2020), as well as through time-resolved cryo-EM and machine-learning approaches. Further, he has expanded his research efforts to explore the mechanism of other enzymes in the ubiquitin system that are disrupted in cancer; these include the Myc regulator UBR5 (EMBO J 2023) and the virally-encoded ubiquitin ligase CRL4-DDB1-pUL145 (Journal of Virology 2022). These and other published studies have produced new structures and insights into how to target enzymes for therapeutics, using PROTACs. As is evident from his publication record, Nick is highly valued as a collaborator by UNC colleagues. He is known for his rigor, innovation, and application of highly developed tools to elucidate protein structure-function relationships. Just as importantly, Nick is generous with his time and effort in support of the department mission, to determine the molecular and cellular basis of human disease and to train the next generation of research scientists.
See you at 4 pm in Bioinformatics.