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Founded in 1982, the Whitehead Institute for Biomedical Research is a non-profit research and teaching institution located in Cambridge, Massachusetts, USA.The Whitehead Institute was founded as a fiscally independent entity from Massachusetts Institute of Technology , and its 17 members hold faculty appointments in the MIT Department of Biology. The Institute is named for businessman and philanthropist Edwin C. "Jack" Whitehead, who selected David Baltimore as the Whitehead Institute's Founding Director. Baltimore chose Gerald Fink, Rudolf Jaenisch, Harvey Lodish, and Robert Weinberg as the Whitehead Institute's Founding Members.The institute is one of the world's leading centers for genomic research. Its Center for Genome Research was active in the Human Genome Project, and reportedly contributed one-third of the human genome sequence announced in June 2000.In June 2003, Eli and Edythe L. Broad pledged $100 million to build the Broad Institute, a joint venture of Whitehead, MIT, Harvard and local teaching hospitals. The new venture's mission is to expand tools for genomic medicine and apply them for the treatment of disease.Less than a decade after its founding, the Whitehead Institute was named the top research institution in the world in molecular biology and genetics, and over a recent 10-year period, papers published by Whitehead scientists had more impact in molecular biology and genetics than those from any of the 15 leading research universities and life science institutes in the United States. Four times since 2009, the Whitehead Institute has been ranked first as the Best Place to Work for Postdocs in USA by The Scientist magazine.Whitehead has a world-renowned faculty that includes the recipients of the 1997, 2010, and 2011 National Medal of Science ; nine members of the National Academy of science ; five Members of the Institute of Medicine ; and seven Fellows of the American Academy of Arts and science . Wikipedia.

Shin C.,Whitehead Institute For Biomedical Research
Molecular cell | Year: 2010

Most metazoan microRNA (miRNA) target sites have perfect pairing to the seed region, located near the miRNA 5' end. Although pairing to the 3' region sometimes supplements seed matches or compensates for mismatches, pairing to the central region has been known to function only at rare sites that impart Argonaute-catalyzed mRNA cleavage. Here, we present "centered sites," a class of miRNA target sites that lack both perfect seed pairing and 3'-compensatory pairing and instead have 11-12 contiguous Watson-Crick pairs to the center of the miRNA. Although centered sites can impart mRNA cleavage in vitro (in elevated Mg(2+)), in cells they repress protein output without consequential Argonaute-catalyzed cleavage. Our study also identified extensively paired sites that are cleavage substrates in cultured cells and human brain. This expanded repertoire of cleavage targets and the identification of the centered site type help explain why central regions of many miRNAs are evolutionarily conserved. Copyright (c) 2010 Elsevier Inc. All rights reserved. Source

Autophagy is an intracellular degradation pathway essential for cellular and energy homoeostasis. It functions in the clearance of misfolded proteins and damaged organelles, as well as recycling of cytosolic components during starvation to compensate for nutrient deprivation. This process is regulated by mTOR (mammalian target of rapamycin)-dependent and mTOR-independent pathways that are amenable to chemical perturbations. Several small molecules modulating autophagy have been identified that have potential therapeutic application in diverse human diseases, including neurodegeneration. Neurodegeneration- associated aggregation-prone proteins are predominantly degraded by autophagy and therefore stimulating this process with chemical inducers is beneficial in a wide range of transgenic disease models. Emerging evidence indicates that compromised autophagy contributes to the aetiology of various neurodegenerative diseases related to protein conformational disorders by causing the accumulation of mutant proteins and cellular toxicity. Combining the knowledge of autophagy dysfunction and the mechanism of drug action may thus be rational for designing targeted therapy. The present review describes the cellular signalling pathways regulating mammalian autophagy and highlights the potential therapeutic application of autophagy inducers in neurodegenerative disorders. ©2013 Biochemical Society. Source

Young R.A.,Whitehead Institute For Biomedical Research | Young R.A.,Massachusetts Institute of Technology
Cell | Year: 2011

Embryonic stem cells and induced pluripotent stem cells hold great promise for regenerative medicine. These cells can be propagated in culture in an undifferentiated state but can be induced to differentiate into specialized cell types. Moreover, these cells provide a powerful model system for studies of cellular identity and early mammalian development. Recent studies have provided insights into the transcriptional control of embryonic stem cell state, including the regulatory circuitry underlying pluripotency. These studies have, as a consequence, uncovered fundamental mechanisms that control mammalian gene expression, connect gene expression to chromosome structure, and contribute to human disease. © 2011 Elsevier Inc. Source

Hanahan D.,Ecole Polytechnique Federale de Lausanne | Hanahan D.,University of California at San Francisco | Weinberg R.A.,Whitehead Institute For Biomedical Research
Cell | Year: 2011

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list - reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. © 2011 Elsevier Inc. Source

Victora G.D.,Whitehead Institute For Biomedical Research | Nussenzweig M.C.,Rockefeller University | Nussenzweig M.C.,Howard Hughes Medical Institute
Annual Review of Immunology | Year: 2012

Germinal centers (GCs) were described more than 125 years ago as compartments within secondary lymphoid organs that contained mitotic cells. Since then, it has become clear that this structure is the site of B cell clonal expansion, somatic hypermutation, and affinity-based selection, the combination of which results in the production of high-affinity antibodies. Decades of anatomical and functional studies have led to an overall model of how the GC reaction and affinity-based selection operate. More recently, the introduction of intravital imaging into the GC field has opened the door to direct investigation of certain key dynamic features of this microanatomic structure, sparking renewed interest in the relationship between cell movement and affinity maturation. We review these and other recent advances in our understanding of GCs, focusing on cellular dynamics and on the mechanism of selection of high-affinity B cells. © 2012 by Annual Reviews. All rights reserved. Source

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