Linyi Gao (ZHANG LAB)

Genome Editing With CRISPR-Cas12a

The recently-characterized Cas12a (Cpf1) nuclease from type V microbial CRISPR-Cas systems offers new opportunities in genome editing beyond Cas9. However, the utility of Cas12a is limited by its requirement of a TTTV sequence motif in the DNA substrate. Here we use a structure-guided approach to alter the DNA-binding interface of Cas12a, introducing new base-specific interactions with non-canonical DNA sequence motifs. These modifications collectively expand the targeting range of Cas12a by three-fold and increase its utility for genome editing.

Nader Morshed (WHITE LAB)

Phosphotyrosine Signaling in Alzheimer’s Disease

Cellular signaling networks play an essential role in brain function and are commonly mediated by protein phosphorylation. Using mass spectrometry, we have quantified protein phosphorylation changes in various models of Alzheimer’s disease. Using computational analysis methods, we have identified signaling pathway changes associated with neuroinflammation and are working to explore their function in the context of Alzheimer’s disease.