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Joseph Sarhan
Tufts University
PyroptosisInterferonProgrammed cell deathEffectorBiology
5Publications
3H-index
72Citations
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Publications 6
Newest
#1Joseph Sarhan (Tufts University)H-Index: 3
#2Anar Mikailov (Lahey Hospital & Medical Center)H-Index: 1
1 CitationsSource
#1Hayley I. Muendlein (Tufts University)H-Index: 3
#2Joseph Sarhan (Tufts University)H-Index: 3
Last. Soroush Tahmasebi (McGill University)H-Index: 8
view all 13 authors...
Summary Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are well known for their capacity to drive necroptosis via mixed-lineage kinase-like domain (MLKL). Recently, RIPK1/3 kinase activity has been shown to drive inflammation via activation of MAPK signaling. However, the regulatory mechanisms underlying this kinase-dependent cytokine production remain poorly understood. In the present study, we establish that the kinase activity of RIPK1/3 regulates cytokine translation in mouse an...
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#1Joseph Sarhan (Tufts University)H-Index: 3
#2Beiyun C. Liu (Tufts University)H-Index: 6
Last. Alexander PoltorakH-Index: 18
view all 11 authors...
Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found tha...
15 CitationsSource
#1Joseph Sarhan (Tufts University)H-Index: 3
#2Beiyun C. Liu (Tufts University)H-Index: 6
Last. Alexander Poltorak (Tufts University)H-Index: 18
view all 11 authors...
Cell death and inflammation are intimately linked during Yersinia infection. Pathogenic Yersinia inhibits the MAP kinase TGFβ-activated kinase 1 (TAK1) via the effector YopJ, thereby silencing cytokine expression while activating caspase-8–mediated cell death. Here, using Yersinia pseudotuberculosis in corroboration with costimulation of lipopolysaccharide and (5Z)-7-Oxozeaenol, a small-molecule inhibitor of TAK1, we show that caspase-8 activation during TAK1 inhibition results in cleavage of bo...
35 CitationsSource
#1Beiyun C. Liu (Tufts University)H-Index: 6
#2Joseph Sarhan (Tufts University)H-Index: 3
Last. Alexander Poltorak (Tufts University)H-Index: 18
view all 3 authors...
Most genetic ablations of interferon (IFN) signaling abolish both the experimentally induced IFN response and constitutive IFN, whose effects are well established in autoimmunity but understudied during infection. In host–pathogen interactions, most IFN-mediated responses are attributed to infection-driven IFN. However, IFNs confer their activity by regulating networks of interferon-stimulated genes (ISGs), a process that requires de novo transcription and translation of both IFN and downstream ...
3 CitationsSource
#1Beiyun C. Liu (Tufts University)H-Index: 6
#2Joseph Sarhan (Tufts University)H-Index: 3
Last. Alexander Poltorak (Tufts University)H-Index: 18
view all 9 authors...
Summary Legionella pneumophila elicits caspase-11-driven macrophage pyroptosis through guanylate-binding proteins (GBPs) encoded on chromosome 3. It has been proposed that microbe-driven IFN upregulates GBPs to facilitate pathogen vacuole rupture and bacteriolysis preceding caspase-11 activation. We show here that macrophage death occurred independently of microbial-induced IFN signaling and that GBPs are dispensable for pathogen vacuole rupture. Instead, the host-intrinsic IFN status sustained ...
19 CitationsSource
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