Doctor of Medicine, Wayne State University School of Medicine (2016)
Bachelor of Science, University of Michigan (2012)
Brendan Visser, Postdoctoral Faculty Sponsor
A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies
2018; Epub ahead of print: 460–71
Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ-tubulin and ε-tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening.
View details for DOI 10.1038/s41588-018-0054-7
View details for PubMedCentralID PMC5862771