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Bruce M. Spiegelman

Bio: Bruce M. Spiegelman is an academic researcher from Harvard University. The author has contributed to research in topics: Adipose tissue & Peroxisome proliferator-activated receptor. The author has an hindex of 179, co-authored 434 publications receiving 158009 citations. Previous affiliations of Bruce M. Spiegelman include University of California, San Francisco & Vassar College.


Papers
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Patent
13 Feb 2003
TL;DR: In this paper, the authors provide novel methods and compositions for modulating type I muscle formation through modulation of PGC-1α activity or expression, as well as methods for identifying compounds that modulate type I and/or type II muscle formation.
Abstract: The invention provides novel methods and compositions for modulating type I muscle formation through modulation of PGC-1α activity or expression. Also provided are methods for identifying compounds that modulate type I muscle formation through modulation of PGC-1α activity or expression. Further provided are methods for treating disorders associated with type I and/or type II muscle formation, as well as transgenic animals expressing PGC-1α in muscle.

24 citations

Journal ArticleDOI
TL;DR: This review examines recent advances in methods for studying transcriptional regulation, with special emphasis on metabolic science, and compares these methods for investigators trying to decide on the best approach for their particular physiological paradigm or model system.

23 citations

Journal ArticleDOI
TL;DR: The beautiful Thorskog Castle just north of Göteborg on the Swedish west coast was the venue for the 134th Nobel Symposium, entitled "The Adipocyte: A Multifunctional Cell."

23 citations

Journal ArticleDOI
TL;DR: The gene, gender, and tissue specificity in the requirement for c‐Fos points to diversity in adaptation mechanisms to stress.
Abstract: Recent studies indicated that c-Fos protein may be mediating stress-elicited transcriptional activation of genes involved in neurotransmitter biosynthesis. However, direct evidence for c-Fos mediating these changes in gene expression has been lacking. Mice with disrupted c-fos gene (+/− or −/− genotypes) were used to examine the effect of immobilization stress on a group of stress-responsive genes. In male adrenals, c-Fos was found not essential for stress-elicited activation of expression of tyrosine hydroxylase, dopamine β-hydroxylase (DBH), phenylethanolamine N-methyltransferase, or neuropeptide Y. In females, immobilization failed to induce adrenal DBH in the c-Fos-deficient mice. In brainstem, c-Fos was indispensable for elevation of DBH mRNA in both genders. The gene, gender, and tissue specificity in the requirement for c-Fos points to diversity in adaptation mechanisms to stress.

22 citations

Book ChapterDOI
TL;DR: The results of these studies indicate that either c-fos is not required for the induction tyrosine hydroxylase (TH) gene expression in AM or that alternative factors are involved, and these studies identify two major promoter elements, an AP1 site and a cyclic AMP/calcium regulatory element, each of which can independently activate TH transcription.
Abstract: Publisher Summary Effects of repeated stress are associated with alterations in gene expression. The effect of immobilization (IMMO) stress on the expression of the genes encoding some catecholamine biosynthetic enzymes, as well as GTPcyclohydrolase I (GTPCH), the rate-limiting enzyme in the tetrahydrobiopterin biosynthetic pathway, has been recognized. This has been studied in the adrenal medulla (AM), a major source of plasma epinephrine; the sympathetic ganglia (SG), a major source of plasma norepinephrine; and the locus ceruleus (LC), the major noradrenergic nucleus in the central nervous system that modulates the response of the hypothalamus and other brain areas to stress. All of these genes have been found to be activated by IMMO. However, there are important differences in the minimal time of IMMO required for the induction of these genes and in the factors mediating the stress response. For example, 5 min of single exposure to stress is found sufficient to elicit a maximal increase in adrenal phenylethanolamine-N-methytransferase (PNMT) mRNA levels. However, to achieve maximal effect on the other genes of interest, longer times were required. The results of these studies indicate that either c-fos is not required for the induction tyrosine hydroxylase (TH) gene expression in AM or that alternative factors are involved. Studies on TH gene expression in cultured cells have identified two major promoter elements, an AP1 site and a cyclic AMP/calcium regulatory element (CRE/CaRE), each of which can independently activate TH transcription.

22 citations


Cited by
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Journal ArticleDOI
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
Abstract: Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

34,830 citations

Journal ArticleDOI
TL;DR: The philosophy and design of the limma package is reviewed, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
Abstract: limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

22,147 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
06 Jun 2013-Cell
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.

9,980 citations

Journal ArticleDOI
TL;DR: Transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob) found that the expression of 1,304 transcripts correlated significantly with body mass.
Abstract: Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-alpha expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.

8,902 citations