Year 2

We have successfully build several human embryonic stem cell lines to improve propagation of stem cells and to model disease. We have identified a tumor suppressor, the deubiquitinase Usp44, as a critical regulator of the stem cell state; the ubiquitin ligase KBTBD8 as an essential component of differentiation pathways leading to neural crest cell specification; and various candidate enzymes as regulators of hESC differentiation. Our results allow us to study molecular origins of severe developmental diseases, such as Treacher Collins Syndrome, forming the foundation for future efforts to isolate small molecule modulators of the disease state.