CRISPR-based drug target discovery in cancer and autoimmunity
A major part of the different projects in the lab involves using CRISPR-based custom screens as a discovery platform to understand complex biological processes and to identify novel drug targets. To facilitate the design of these custom screens, we have developed a freely accessible web-based software called Green Listed. A review describing bioinformatics tools we use designing and analyzing hypothesis-driven CRISPR screens can be found in Iyer VS et al., 2020). Related CRISPR plasmids that we have deposited can be found at the non-profit repository Addgene.
Examples of how we work with CRISPR for discovery in vitro and in vivo is found in Shen Y et al., 2021, where we describe the Rapid CRISPR Competitive/RCC assay and the ImmunoCRISPR/iCR model system), as well as in Jiang L et al., 2021, Cancer Research, where we study the CRISPR DNA damage response).
Several projects in the lab also relate to our interest in signaling downstream of the IL-4 receptor (IL-4R). The basis for this interest was the unexpected finding that the expression of the IL-4R is essential for the activity of a drug (IVIG) used to treat patients with autoimmune disease and that the expression of this receptor is highly regulated during inflammation (Anthony RM et al., 2011, Nature, and Wermeling F et al., 2013, PNAS). More recently we published a study describing how IL-4 can affect neutrophils, and consequences of this in the autoimmune setting (Panda SK et al., 2020, PNAS).