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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
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Journal ArticleDOI
14 Jul 1994-Nature
TL;DR: A new Jak family kinase is described, and it is demonstrated that Jak-3, and to a lesser extent Jak-1, are tyrosine phosphorylated and Jak- 3 is activated in the responses to interleukin-2 and interLEukin–4 in T cells and myeloid cells.
Abstract: Many cytokines function through interaction with receptors of the cytokine receptor superfamily. Although lacking catalytic domains, cytokine receptors couple ligand binding to induction of protein tyrosine phosphorylation. Recent studies have shown that one or more of the Janus kinase family members (Jaks) associate with cytokine receptors and are tyrosine phosphorylated and activated following ligand binding. Here we describe a new Jak family kinase, Jak-3, and demonstrate that Jak-3, and to a lesser extent Jak-1, are tyrosine phosphorylated and Jak-3 is activated in the responses to interleukin-2 and interleukin-4 in T cells and myeloid cells. Jak-3 activation requires the serine-rich, membrane-proximal domain of the interleukin-2 receptor beta-chain, but does not require the acidic domain that is required for association and activation of Src family kinases.

591 citations

Journal ArticleDOI
TL;DR: A 'loophole' in the TLR pathway that is advantageous to intracellular pathogens is reported that favored host survival during T. gondii infection and decreased lung bacterial load during tuberculosis infection.
Abstract: Toll-like receptor (TLR) signaling in macrophages is required for antipathogen responses, including the biosynthesis of nitric oxide from arginine, and is essential for immunity to Mycobacterium tuberculosis, Toxoplasma gondii and other intracellular pathogens. Here we report a 'loophole' in the TLR pathway that is advantageous to these pathogens. Intracellular pathogens induced expression of the arginine hydrolytic enzyme arginase 1 (Arg1) in mouse macrophages through the TLR pathway. In contrast to diseases dominated by T helper type 2 responses in which Arg1 expression is greatly increased by interleukin 4 and 13 signaling through the transcription factor STAT6, TLR-mediated Arg1 induction was independent of the STAT6 pathway. Specific elimination of Arg1 in macrophages favored host survival during T. gondii infection and decreased lung bacterial load during tuberculosis infection.

587 citations

Journal ArticleDOI
TL;DR: It is demonstrated that enhanced gene transfer into mammalian target cells is due to direct binding of retroviral particles to sequences within the fibronectin molecule.
Abstract: Hematopoietic cells are important targets for genetic modification with retroviral vectors. Attempts at human gene therapy of stem cells have achieved limited success partly because of low gene transfer efficiency. Chymotryptic fragments of the extracellular matrix molecule fibronectin used during infection have been shown to increase transduction of human hematopoietic progenitor cells. Here, we demonstrate that this enhanced gene transfer into mammalian target cells is due to direct binding of retroviral particles to sequences within the fibronectin molecule. Transduction of mammalian cells, including murine long-term repopulating hematopoietic cells, is greatly enhanced when cells are adherent to chimeric fragments containing these retroviral binding sequences. In addition, colocalization of retrovirus and target cells on fibronectin peptides allows targeted transduction of specific cell types by exploiting unique ligand/receptor interactions.

587 citations

Journal ArticleDOI
TL;DR: The consequence of phagocytosis of dead cells is strongly affected by those components of the autophagy pathway involved in LAP, and the engagement of LAP upon uptake of apoptotic, necrotic, and RIPK3-dependent nec rotic cells by macrophages is described.
Abstract: The recognition and clearance of dead cells is a process that must occur efficiently to prevent an autoimmune or inflammatory response. Recently, a process was identified wherein the autophagy machinery is recruited to pathogen-containing phagosomes, termed MAPLC3A (LC3)-associated phagocytosis (LAP), which results in optimal degradation of the phagocytosed cargo. Here, we describe the engagement of LAP upon uptake of apoptotic, necrotic, and RIPK3-dependent necrotic cells by macrophages. This process is dependent on some members of the classical autophagy pathway, including Beclin1, ATG5, and ATG7. In contrast, ULK1, despite being required for autophagy, is dispensable for LAP induced by uptake of microbes or dead cells. LAP is required for efficient degradation of the engulfed corpse, and in the absence of LAP, engulfment of dead cells results in increased production of proinflammatory cytokines and decreased production of anti-inflammatory cytokines. LAP is triggered by engagement of the TIM4 receptor by either phosphatidylserine (PtdSer)-displaying dead cells or PtdSer-containing liposomes. Therefore, the consequence of phagocytosis of dead cells is strongly affected by those components of the autophagy pathway involved in LAP.

585 citations

Journal ArticleDOI
15 Oct 2015-Nature
TL;DR: Current efforts that focus on the processes required to appropriately act on pharmacogenomic variability in the clinic are moving away from discovery and towards implementation of an evidenced-based strategy for improving the use of medications, thereby providing a cornerstone for precision medicine.
Abstract: After decades of discovery, inherited variations have been identified in approximately 20 genes that affect about 80 medications and are actionable in the clinic. And some somatically acquired genetic variants direct the choice of 'targeted' anticancer drugs for individual patients. Current efforts that focus on the processes required to appropriately act on pharmacogenomic variability in the clinic are moving away from discovery and towards implementation of an evidenced-based strategy for improving the use of medications, thereby providing a cornerstone for precision medicine.

582 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
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202333
2022108
20211,277
20201,136
2019965
2018877