Identification of novel Wnt signaling regulators

Although the Wnt signaling pathway has been studied for many years, new Wnt regulators are constantly being discovered.  We utilize different screening approaches in order to identify novel components of the Wnt cascade, among them are a CRISPR/Cas9 library to silence genes that inhibit the signal and a differential functional library that activates the Wnt pathway. 

Carboxypeptidase E (CPE) is one of the new Wnt signaling regulators that were isolated and characterized.

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Carboxypeptidase E (CPE) and its substrate (NeuroPeptide Y) localize to lysosomes.

Our most recent genetic screen using a Human Genome-wide CRISPR- pooled Knock-out Library (GeCKO) identified several exiting new Wnt regulators that are currently being studied in our lab. The screen results were analyzed to determine up- and down-regulators of the Wnt cascade (A-B). The top scoring candidates were validated (C) and tested for their ability to affect Wnt activity (D).

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