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Institution

University of Texas Southwestern Medical Center

HealthcareDallas, Texas, United States
About: University of Texas Southwestern Medical Center is a healthcare organization based out in Dallas, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 39107 authors who have published 75242 publications receiving 4497256 citations. The organization is also known as: UT Southwestern & UT Southwestern Medical School.


Papers
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Journal ArticleDOI
09 Jul 1999-Cell
TL;DR: The ocular phenotype in abcr knockout mice is characterized and data suggest that RmP functions as an outwardly directed flippase for N-retinylidene-PE, and ABCR-mediated retinal degeneration may result from "poisoning" of the RPE due to A2-E accumulation.

846 citations

Journal ArticleDOI
TL;DR: Among children with later‐onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group.
Abstract: Background Nusinersen is an antisense oligonucleotide drug that modulates pre–messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). Methods We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale–Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates impro...

846 citations

Journal ArticleDOI
TL;DR: It is shown that environmental stress and alterations in DNA repair genes associate with distinct mutation spectra, and multiple novel mutated genes in PDA are identified, with select genes harbouring prognostic significance.
Abstract: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and insights into both disease etiology and targeted intervention are needed. A total of 109 micro-dissected PDA cases were subjected to whole-exome sequencing. Microdissection enriches tumour cellularity and enhances mutation calling. Here we show that environmental stress and alterations in DNA repair genes associate with distinct mutation spectra. Copy number alterations target multiple tumour suppressive/oncogenic loci; however, amplification of MYC is uniquely associated with poor outcome and adenosquamous subtype. We identify multiple novel mutated genes in PDA, with select genes harbouring prognostic significance. RBM10 mutations associate with longer survival in spite of histological features of aggressive disease. KRAS mutations are observed in >90% of cases, but codon Q61 alleles are selectively associated with improved survival. Oncogenic BRAF mutations are mutually exclusive with KRAS and define sensitivity to vemurafenib in PDA models. High-frequency alterations in Wnt signalling, chromatin remodelling, Hedgehog signalling, DNA repair and cell cycle processes are observed. Together, these data delineate new genetic diversity of PDA and provide insights into prognostic determinants and therapeutic targets.

844 citations

Journal ArticleDOI
20 Sep 2013-Science
TL;DR: Cells from cGAS-deficient mice, including fibroblasts, macrophages, and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection, and were more susceptible to lethal infection with herpes simplex virus 1 than wild-type mice.
Abstract: Invasion of microbial DNA into the cytoplasm of animal cells triggers a cascade of host immune reactions that help clear the infection; however, self DNA in the cytoplasm can cause autoimmune diseases. Biochemical approaches led to the identification of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses. Here, we show that cells from cGAS-deficient (cGas(-/-)) mice, including fibroblasts, macrophages, and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection. cGas(-/-) mice were more susceptible to lethal infection with herpes simplex virus 1 (HSV1) than wild-type mice. We also show that cGAMP is an adjuvant that boosts antigen-specific T cell activation and antibody production in mice.

844 citations

Journal ArticleDOI
28 May 1999-Science
TL;DR: It is shown that by gestational day 11.5, mice lacking endoglin die from defective vascular development, however, in contrast to mice lacking TGF-beta, vasculogenesis was unaffected and suggest a pathogenic mechanism for HHT1.
Abstract: Endoglin is a transforming growth factor-beta (TGF-beta) binding protein expressed on the surface of endothelial cells. Loss-of-function mutations in the human endoglin gene ENG cause hereditary hemorrhagic telangiectasia (HHT1), a disease characterized by vascular malformations. Here it is shown that by gestational day 11.5, mice lacking endoglin die from defective vascular development. However, in contrast to mice lacking TGF-beta, vasculogenesis was unaffected. Loss of endoglin caused poor vascular smooth muscle development and arrested endothelial remodeling. These results demonstrate that endoglin is essential for angiogenesis and suggest a pathogenic mechanism for HHT1.

843 citations


Authors

Showing all 39410 results

NameH-indexPapersCitations
Eugene Braunwald2301711264576
Joseph L. Goldstein207556149527
Eric N. Olson206814144586
Craig B. Thompson195557173172
Thomas C. Südhof191653118007
Scott M. Grundy187841231821
Michael S. Brown185422123723
Eric Boerwinkle1831321170971
Jiaguo Yu178730113300
John J.V. McMurray1781389184502
Eric J. Nestler178748116947
John D. Minna169951106363
Yuh Nung Jan16246074818
Andrew P. McMahon16241590650
Elliott M. Antman161716179462
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023114
2022406
20215,247
20204,674
20194,094
20183,400