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.
Massachusetts Institute of Technology and Whitehead Institute For Biomedical Research | Date: 2016-09-23
Compositions and methods for modified dendrimer nanoparticle (MDNP) delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules to the cells of a subject have been developed. MDNPs efficiently drive proliferation of antigen-specific T cells against intracellular antigen, and potentiate antigen-specific antibody responses. MDNPs can be multiplexed to deliver two or more different repRNAs to modify expression kinetics of encoded antigens and to simultaneous deliver repRNAs and mRNAs including the same UTR elements that promote expression of encoded antigens.
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.
Erlich Y.,Whitehead Institute For Biomedical Research |
Narayanan A.,Princeton University
Nature Reviews Genetics | Year: 2014
We are entering an era of ubiquitous genetic information for research, clinical care and personal curiosity. Sharing these data sets is vital for progress in biomedical research. However, a growing concern is the ability to protect the genetic privacy of the data originators. Here, we present an overview of genetic privacy breaching strategies. We outline the principles of each technique, indicate the underlying assumptions, and assess their technological complexity and maturation. We then review potential mitigation methods for privacy-preserving dissemination of sensitive data and highlight different cases that are relevant to genetic applications. © 2014 Macmillan Publishers Limited. All rights reserved.
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.
McKinley K.L.,Whitehead Institute For Biomedical Research |
Cheeseman I.M.,Whitehead Institute For Biomedical Research
Cell | Year: 2014
To ensure the stable transmission of the genome during vertebrate cell division, the mitotic spindle must attach to a single locus on each chromosome, termed the centromere. The fundamental requirement for faithful centromere inheritance is the controlled deposition of the centromere-specifying histone, CENP-A. However, the regulatory mechanisms that ensure the precise control of CENP-A deposition have proven elusive. Here, we identify polo-like kinase 1 (Plk1) as a centromere-localized regulator required to initiate CENP-A deposition in human cells. We demonstrate that faithful CENP-A deposition requires integrated signals from Plk1 and cyclin-dependent kinase (CDK), with Plk1 promoting the localization of the key CENP-A deposition factor, the Mis18 complex, and CDK inhibiting Mis18 complex assembly. By bypassing these regulated steps, we uncoupled CENP-A deposition from cell-cycle progression, resulting in mitotic defects. Thus, CENP-A deposition is controlled by a two-step regulatory paradigm comprised of Plk1 and CDK that is crucial for genomic integrity. © 2014 Elsevier Inc.
Cheeseman I.M.,Whitehead Institute For Biomedical Research
Cold Spring Harbor Perspectives in Biology | Year: 2014
A critical requirement for mitosis is the distribution of genetic material to the two daughter cells. The central player in this process is the macromolecular kinetochore structure, which binds to both chromosomal DNA and spindle microtubule polymers to direct chromosome alignment and segregation. This review will discuss the key kinetochore activities required for mitotic chromosome segregation, including the recognition of a specific site on each chromosome, kinetochore assembly and the formation of kinetochore-microtubule connections, the generation of force to drive chromosome segregation, and the regulation of kinetochore function to ensure that chromosome segregation occurs with high fidelity. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.
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.
Gehring M.,Whitehead Institute For Biomedical Research
Annual Review of Genetics | Year: 2013
Imprinted gene expression-the biased expression of alleles dependent on their parent of origin-is an important type of epigenetic gene regulation in flowering plants and mammals. In plants, genes are imprinted primarily in the endosperm, the triploid placenta-like tissue that surrounds and nourishes the embryo during its development. Differential allelic expression is correlated with active DNA demethylation by DNA glycosylases and repressive targeting by the Polycomb group proteins. Imprinted gene expression is one consequence of a large-scale remodeling to the epigenome, primarily directed at transposable elements, that occurs in gametes and seeds. This remodeling could be important for maintaining the epigenome in the embryo as well as for establishing gene imprinting. © 2013 by Annual Reviews. All rights reserved.
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.
Weinberg R.A.,Whitehead Institute For Biomedical Research |
Weinberg R.A.,Massachusetts Institute of Technology
Cell | Year: 2014
Cell has celebrated the powers of reductionist molecular biology and its major successes for four decades. Those who have participated in cancer research during this period have witnessed wild fluctuations from times where endless inexplicable phenomenology reigned supreme to periods of reductionist triumphalism and, in recent years, to a move back to confronting the endless complexity of this disease. © 2014 Elsevier Inc.