Clinical and Translational Science Network

Mammalian development relies on the precise execution of highly coordinated cell-fate decisions by stem cells, which can undergo self-renewal, reversibly exit into a quiescent state, or terminally commit to a cell differentiation program. To orchestrate these decisions, stem cells make frequent use of ubiquitylation, an essential post-translational modification that alters the stability, activity, localization, or interaction landscape of target proteins. My lab combines human genetics, pluripotent stem cell culture, proteomic, and biochemical approaches to determine the molecular underpinnings of ubiquitin-dependent cell-fate choices involved in neural crest and neuronal differentiation. I will present our latest findings on how variants in specific components of the ubiquitin conjugation and deconjugation machinery result in congenital disorders affecting central nervous system and craniofacial development and how we can leverage these mutations to uncover novel regulatory principles of early embryonic differentiation events.

Learning Objectives:

• Strategies to leverage human disease genetics to identify basic principles of cellular signaling during embryogenesis will be introduced using developmental disorders as example.
• Participants will learn about the essential post-translational modifier ubiquitin, the role of ubiquitylation in cellular signaling and in the development of the embryonic ectoderm, and how dysregulation of ubiquitylation causes neurodevelopmental and craniofacial diseases.