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Michael Karin

Bio: Michael Karin is an academic researcher from University of California, San Diego. The author has contributed to research in topics: IκB kinase & Signal transduction. The author has an hindex of 236, co-authored 704 publications receiving 226485 citations. Previous affiliations of Michael Karin include Sanford-Burnham Institute for Medical Research & University of California, Los Angeles.


Papers
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Patent
18 Jun 2007
TL;DR: In this paper, a method for activating Toll-like receptor 4 via cholesterol-dependent cytolysins isolated from a Gram-positive bacteria is presented, and methods for use of such composition in inhibiting binding and/or interaction of Toll-Like receptor 4 with endotoxin are provided.
Abstract: Methods for activating Toll-like receptor 4 via cholesterol-dependent cytolysins isolated from a Gram-positive bacteria are provided. In addition compositions containing an isolated cholesterol-dependent cytolysin or a fragment thereof or a mimetic of the cytolysin or fragment thereof and methods for use of such composition in inhibiting binding and/or interaction of Toll-like receptor 4 with endotoxin are provided. Methods for identifying modulators of Toll-like receptor 4 activation by a cholesterol-dependent cytolysin and use of such modulators in treatment of septicemia and/or septic shock are also provided.

2 citations

Patent
12 Oct 2005
TL;DR: In this paper, a method for identifying compounds and methods for using compounds which modulate interaction of lethal factor and anthrolysin O in the treatment and prevention of anthrax diseases are provided.
Abstract: Compounds, methods for identifying compounds and methods for using compounds which modulate interaction of lethal factor and anthrolysin O in the treatment and prevention of anthrax diseases are provided.

2 citations

Journal ArticleDOI
TL;DR: The data suggest that miR-135b is a key molecule whose activation is downstream of oncogenes and oncosuppressor genes frequently altered in CRC and represents the first in vivo study for the use of antimiRs in CRC treatment.
Abstract: 457 Background: MicroRNAs (miRs) are small non coding RNAs involved in cell homeostasis. miRs are deregulated in colorectal cancer (CRC). Our study aimed at identifying miRs with a driver role in carcinogenesis altered by similar mechanisms in both human and mouse CRC. Goal of the study was to use CRC mouse models for the pre-clinical development of anti-miRs as therapeutic drugs. Methods: Azoximetane (AOM)/Dextran-Sulfate (DSS) treated mice or CDX2-CRE/APC-/- mice were used to study inflammation-associated and sporadic APC-related CRC. Human Inflammatory Bowel Disease associated (n=30), and sporadic (n=90) CRC with their matched normal tissues were collected according to Good Clinical Practice recommendation and subjected to RNA extraction using Trizol. miR and gene expression profiling was assessed by nCounter technology (Nanostring Seattle). Anti-miR-135b and scrambled probes for in vivo studies were synthesized by Girindus. Results: miRs profiling from AOM/DSS and CDX2-CRE/APC-/- CRC. revealed that mi...

2 citations

Journal ArticleDOI
TL;DR: It is reported that conditional knockout of IKKβ in limb bud mesenchymal cells results in the upregulation of monocyte chemoattractant protein-5 (MCP-5) in the perichondrium, which in turn inhibits the growth of longitudinal bone by compromising chondrocyte hypertrophy and increasing the apoptosis of chONDrocytes within the growth plate.
Abstract: IκB kinase β (IKKβ) is a catalytic subunit of the IKK complex, which activates nuclear factor-κB (NF-κB). Although its role in osteoclastogenesis is well established, the role of IKKβ in bone formation is poorly understood. Here, we report that conditional knockout of Ikkβ in limb bud mesenchymal cells results in the upregulation of monocyte chemoattractant protein-5 (MCP-5) in the perichondrium, which in turn inhibits the growth of longitudinal bone by compromising chondrocyte hypertrophy and increasing the apoptosis of chondrocytes within the growth plate. Contrary to expectations, IKKβ in cells of chondrocyte or osteoblast lineage was dispensable for bone growth. On the other hand, ex vivo experiments confirmed the role of MCP-5 in the growth of longitudinal bone. Furthermore, an in vitro study demonstrated that the action of IKKβ on MCP-5 is cell autonomous. Collectively, our results provide evidence for a previously unrecognized role of IKKβ in the regulation of the growth plate that is mediated through stimulation-independent downregulation of MCP-5 in the perichondrium.

2 citations

Journal ArticleDOI
TL;DR: This article showed that Triclosan (TCS), a high-volume antimicrobial additive that has been detected in human breastmilk, can be efficiently transferred by lactation to newborn mice, causing significant fatty liver (FL) during the suckling period.
Abstract: Here we show that Triclosan (TCS), a high-volume antimicrobial additive that has been detected in human breastmilk, can be efficiently transferred by lactation to newborn mice, causing significant fatty liver (FL) during the suckling period. These findings are relevant since pediatric non-alcoholic fatty liver disease (NAFLD) is escalating in the United States, with a limited mechanistic understanding. Lactational delivery stimulated hepatosteatosis, triglyceride accumulation, endoplasmic reticulum (ER) stress, signs of inflammation, and liver fibrosis. De novo lipogenesis (DNL) induced by lactational TCS exposure is shown to be mediated in a PERK-eIF2α-ATF4-PPARα cascade. The administration of obeticholic acid (OCA), a potent FXR agonist, as well as activation of intestinal mucosal-regenerative gp130 signaling, led to reduced liver ATF4 expression, PPARα signaling, and DNL when neonates were exposed to TCS. It is yet to be investigated but mother to child transmission of TCS or similar toxicants may underlie the recent increases in pediatric NAFLD.

2 citations


Cited by
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Journal ArticleDOI
04 Mar 2011-Cell
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.

51,099 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.

12,240 citations

Journal ArticleDOI
24 Feb 2006-Cell
TL;DR: New insights into innate immunity are changing the way the way the authors think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.

10,685 citations

Journal ArticleDOI
TL;DR: The mechanisms of ROS generation and removal in plants during development and under biotic and abiotic stress conditions are described and the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast.
Abstract: Several reactive oxygen species (ROS) are continuously produced in plants as byproducts of aerobic metabolism. Depending on the nature of the ROS species, some are highly toxic and rapidly detoxified by various cellular enzymatic and nonenzymatic mechanisms. Whereas plants are surfeited with mechanisms to combat increased ROS levels during abiotic stress conditions, in other circumstances plants appear to purposefully generate ROS as signaling molecules to control various processes including pathogen defense, programmed cell death, and stomatal behavior. This review describes the mechanisms of ROS generation and removal in plants during development and under biotic and abiotic stress conditions. New insights into the complexity and roles that ROS play in plants have come from genetic analyses of ROS detoxifying and signaling mutants. Considering recent ROS-induced genome-wide expression analyses, the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast.

9,908 citations