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Alexander Poltorak
Tufts University
Innate immune systemMolecular biologyImmunologyBiologyCell biology
43Publications
18H-index
8,312Citations
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Publications 44
Newest
#1Hayley I. Muendlein (Tufts University)H-Index: 3
#2David Jetton (Tufts University)
Last. Alexander Poltorak (Tufts University)H-Index: 18
view all 7 authors...
Cell death and inflammation are interdependent host responses to infection. During pyroptotic cell death, interleukin-1β (IL-1β) release occurs through caspase-1 and caspase-11–mediated gasdermin D pore formation. In vivo, responses to lipopolysaccharide (LPS) result in IL-1β secretion. In vitro, however, murine macrophages require a second “danger signal” for the inflammasome-driven maturation of IL-1β. Recent reports have shown caspase-8–mediated pyroptosis in LPS-activated macrophages but hav...
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#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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#1Daniil NikitinH-Index: 3
#2Andrew GarazhaH-Index: 10
Last. Anton BuzdinH-Index: 26
view all 10 authors...
In the article ‘Retroelement—Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution,’ a number of transcription factor binding sites (TFBS) mapped on all retroelement classes were incorrectly calculated as sum of TFBS numbers separately mapped on LINEs, SINEs and LTR retrotransposons/endogenous retroviruses (LR/ERVs) [...]
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#1Daniil NikitinH-Index: 3
#2Andrew GarazhaH-Index: 10
Last. Anton BuzdinH-Index: 26
view all 10 authors...
Background: Retroelements (REs) are transposable elements occupying ~40% of the human genome that can regulate genes by providing transcription factor binding sites (TFBS). RE-linked TFBS profile can serve as a marker of gene transcriptional regulation evolution. This approach allows for interrogating the regulatory evolution of organisms with RE-rich genomes. We aimed to characterize the evolution of transcriptional regulation for human genes and molecular pathways using RE-linked TFBS accumula...
5 CitationsSource
#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
#1Alexander Poltorak (Tufts University)H-Index: 18
#2Svetlana ApalkoH-Index: 1
Last. Sergei Sherbak (SPbU: Saint Petersburg State University)H-Index: 1
view all 3 authors...
Classical inbred mouse strains have historically been instrumental in mapping immunological traits. However, most of the classical strains originate from a relatively limited number of founder animals, largely within the Mus musculus domesticus subspecies. Therefore, their genetic diversity is ultimately limited. For this reason, it is not feasible to use these mice for exhaustive interrogation of immune signaling pathways. In order to investigate networks through forward genetic analysis, large...
1 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
#1Daniil Nikitin (EIMB: Engelhardt Institute of Molecular Biology)H-Index: 3
#2Dmitry Penzar (MSU: Moscow State University)H-Index: 3
Last. Anton BuzdinH-Index: 26
view all 9 authors...
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBS). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. Using ENCODE data, we identified ~2 million TFBS overlapping with putatively...
9 CitationsSource
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