scispace - formally typeset
Search or ask a question
Institution

St. Jude Children's Research Hospital

HealthcareMemphis, Tennessee, United States
About: St. Jude Children's Research Hospital is a healthcare organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Virus. The organization has 9344 authors who have published 19233 publications receiving 1233399 citations. The organization is also known as: St. Jude Children's Hospital & St. Jude Hospital.


Papers
More filters
Journal ArticleDOI
TL;DR: It is demonstrated that renal tubules do not undergo sensitization to necroptosis upon genetic ablation of either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does not protect freshly isolated tubules from hypoxic injury, and ferroptosis mediates postischemic and toxic renal necrosis.
Abstract: Receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is thought to be the pathophysiologically predominant pathway that leads to regulated necrosis of parenchymal cells in ischemia-reperfusion injury (IRI), and loss of either Fas-associated protein with death domain (FADD) or caspase-8 is known to sensitize tissues to undergo spontaneous necroptosis. Here, we demonstrate that renal tubules do not undergo sensitization to necroptosis upon genetic ablation of either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does not protect freshly isolated tubules from hypoxic injury. In contrast, iron-dependent ferroptosis directly causes synchronized necrosis of renal tubules, as demonstrated by intravital microscopy in models of IRI and oxalate crystal-induced acute kidney injury. To suppress ferroptosis in vivo, we generated a novel third-generation ferrostatin (termed 16-86), which we demonstrate to be more stable, to metabolism and plasma, and more potent, compared with the first-in-class compound ferrostatin-1 (Fer-1). Even in conditions with extraordinarily severe IRI, 16-86 exerts strong protection to an extent which has not previously allowed survival in any murine setting. In addition, 16-86 further potentiates the strong protective effect on IRI mediated by combination therapy with necrostatins and compounds that inhibit mitochondrial permeability transition. Renal tubules thus represent a tissue that is not sensitized to necroptosis by loss of FADD or caspase-8. Finally, ferroptosis mediates postischemic and toxic renal necrosis, which may be therapeutically targeted by ferrostatins and by combination therapy.

720 citations

Journal ArticleDOI
TL;DR: Data identify Arg1 as the essential suppressive mediator of alternatively activated macrophages (AAM) and demonstrate that Arg1-expressing macrophage function as suppressors rather than inducers of Th2-dependent inflammation and fibrosis.
Abstract: Macrophage-specific expression of Arginase-1 is commonly believed to promote inflammation, fibrosis, and wound healing by enhancing L-proline, polyamine, and Th2 cytokine production. Here, however, we show that macrophage-specific Arg1 functions as an inhibitor of inflammation and fibrosis following infection with the Th2-inducing pathogen Schistosoma mansoni. Although susceptibility to infection was not affected by the conditional deletion of Arg1 in macrophages, Arg1(-/flox);LysMcre mice died at an accelerated rate. The mortality was not due to acute Th1/NOS2-mediated hepatotoxicity or endotoxemia. Instead, granulomatous inflammation, liver fibrosis, and portal hypertension increased in infected Arg1(-/flox);LysMcre mice. Similar findings were obtained with Arg1(flox/flox);Tie2cre mice, which delete Arg1 in all macrophage populations. Production of Th2 cytokines increased in the infected Arg1(-/flox);LysMcre mice, and unlike alternatively activated wild-type macrophages, Arg1(-/flox);LysMcre macrophages failed to inhibit T cell proliferation in vitro, providing an underlying mechanism for the exacerbated Th2 pathology. The suppressive activity of Arg1-expressing macrophages was independent of IL-10 and TGF-beta1. However, when exogenous L-arginine was provided, T cell proliferation was restored, suggesting that Arg1-expressing macrophages deplete arginine, which is required to sustain CD4(+) T cell responses. These data identify Arg1 as the essential suppressive mediator of alternatively activated macrophages (AAM) and demonstrate that Arg1-expressing macrophages function as suppressors rather than inducers of Th2-dependent inflammation and fibrosis.

717 citations

Journal ArticleDOI
11 Nov 1993-Nature
TL;DR: A cell line is produced which lacks the protein tyrosine kinase JAK1 and is completely defective in interferon response, but implementation of this mutant with JAK2 restored the response, establishing the requirement for JAK 1 in both the interferons-& alpha;/&# 38; beta; and -& #38; gamma; signal transduction pathways.
Abstract: We have produced a cell line which lacks the protein tyrosine kinase JAK1 and is completely defective in interferon response. Complementation of this mutant with JAK1 restored the response, establishing the requirement for JAK1 in both the interferon-α/β and -γ signal transduction pathways. The reciprocal interdependence between JAK1 and Tyk2 activities in the interferon-α pathway, and between JAK1 and JAK2 in the interferon-γ pathway, may reflect a requirement for these kinases in the correct assembly of interferon receptor complexes.

710 citations

Journal ArticleDOI
TL;DR: The two products of the Ink4a-Arf locus, p16(Ink4a) and p19(Arf) (p14(ARF) in humans), are potent tumor suppressors that regulate the activities of the retinoblastoma protein and the p53 transcription factor as mentioned in this paper.

709 citations

Journal ArticleDOI
01 Jun 1998-Immunity
TL;DR: Virus-specific CD8+ effector T cells are enriched in the lungs of mice with primary influenza pneumonia, though later detection of memory T cells (mCTL) in the mediastinal lymph nodes (MLN) or spleen by peptide-based staining protocols is at the limits of flow cytometric analysis.

707 citations


Authors

Showing all 9410 results

NameH-indexPapersCitations
Richard A. Flavell2311328205119
David Baltimore203876162955
John C. Reed190891164382
Joan Massagué189408149951
Stuart H. Orkin186715112182
Douglas R. Green182661145944
Richard K. Wilson173463260000
Todd R. Golub164422201457
Robert G. Webster15884390776
Elaine R. Mardis156485226700
David Cella1561258106402
Rafi Ahmed14663393190
Ching-Hon Pui14580572146
Yoshihiro Kawaoka13988375087
Seth M. Steinberg13793680148
Network Information
Related Institutions (5)
Memorial Sloan Kettering Cancer Center
65.3K papers, 4.4M citations

96% related

National Institutes of Health
297.8K papers, 21.3M citations

96% related

Baylor College of Medicine
94.8K papers, 5M citations

95% related

University of Texas MD Anderson Cancer Center
92.5K papers, 4.7M citations

95% related

University of Texas Southwestern Medical Center
75.2K papers, 4.4M citations

95% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202333
2022108
20211,277
20201,136
2019965
2018877