The proteomic landscape of interferon signaling in primary T cells

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B243
Abstract ID: 4942

Presenting Author:
David E Gordon , Assistant Professor at Emory Univ. Sch. of Med.

Abstract:

Interferon signaling has a central role in host defense against pathogens and modulation of inflammation, and it also impacts angiogenesis, carcinogenesis, and response to cancer therapeutics. Despite the physiological importance of interferon, the diverse molecular pathways mediating interferon signaling remain poorly defined, complicating understanding and treatment of interferon-mediated pathology. To address this knowledge gap, we applied mass-spectrometry based proteomics to map the phosphorylation pathways downstream of type-I interferon treatment in primary human T cells. Through time-course analysis of our phosphoproteomic data, we observe profound and rapid changes across over 1,300 phosphosites, revealing a dramatic rewiring of the proteome caused by interferon treatment. Clustering analysis of our phosphoproteomic data highlights numerous immunity-associated proteins, many of which have not previously been associated with interferon signaling, co-clustering with canonical STAT phosphosites (e.g. STAT1-Y701, STAT3-Y705, and STAT4-Y693). This rich dataset highlights the complexity of interferon signaling, and forms the basis for a drastically improved understanding of interferon-regulated pathways. In follow up work, we are also applying experimental genetics paired with phosphoproteomic analysis, as well as proteome-wide interaction studies, to delineate the network architecture of type-I interferon signaling.