Eric Goedken, PhD
Principal Research Scientist, AbbVie
Boston, MA

Students in Action seminar host: Jillian Johnson

New Target Identification in Drug Discovery: Small Molecule and CRISPR Phenotypic Screens in the IL-17 Pathway

The recent clinical success of IL-17A neutralizing biologics in psoriasis has underlined its importance as a target for drug discovery. While many studies have focused on the differentiation and trafficking of IL-17A producing T-helper 17 (Th17) cells to psoriatic tissue, less is known about IL-17A initiated signaling events in cells such as keratinocytes & fibroblasts that lead to the manifestation of psoriasis. As such, our interest was to discover potential signaling nodes downstream of IL-17A that contribute to disease pathogenesis. Using a combination of IL-17A and TNF to stimulate primary human epidermal keratinocytes we employed two different phenotypic screening approaches. An annotated library of small molecule compounds was screened by measuring reduced secretion of the pro-inflammatory chemokine interleukin-8 (IL-8). Subsequently, a library of protein kinases was screened in a pooled format utilizing CRISPR-Cas9 with IL-8 intracellular staining as the readout.

In my seminar, I will compare/contrast the findings from these two orthogonal methods and highlight a target with novel involvement in this pathway that we have identified in this manner.