Cambridge, MA, United States

Whitehead Institute For Biomedical Research

wi.mit.edu/
Cambridge, MA, United States

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.

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Patent
Whitehead Institute For Biomedical Research | Date: 2017-02-09

The invention provides compositions and methods of use in reprogramming somatic cells. Compositions and methods of the invention are of use, e.g., for generating or modulating (e.g., enhancing) generation of induced pluripotent stem cells by reprogramming somatic cells. The reprogrammed somatic cells are useful for a number of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a pluripotent state and/or enhances the speed and/or efficiency of reprogramming. Certain of the compositions and methods relate to modulating the Wnt pathway.


Patent
Whitehead Institute For Biomedical Research | Date: 2017-07-19

The present invention provides methods of identifying modulators of mTORC1 based upon their effect on GATOR2-Sestrin binding or Sestrin-leucine binding; and the use of such modulators to alter mTORC1 activity in a cell and to treat disease and conditions that are effected by mTORC1 activity.


Patent
Whitehead Institute For Biomedical Research | Date: 2017-07-19

Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human ApoE protein. In some embodiments the polypeptide comprises ApoE2. In some embodiments the polypeptide comprises ApoE3. In some embodiments the polypeptide comprises ApoE4. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress Apo-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimers disease. Also disclosed are methods of screening yeast cells to identify genetic suppressors or enhancers of ApoE-induced toxicity. Also disclosed are genetic suppressors or enhancers of ApoE-induced toxicity identified using the methods, and human homologs thereof. Also disclosed are methods of identifying compounds that modulate expression or activity of genetic modifiers of ApoE- induced toxicity.


Patent
Whitehead Institute For Biomedical Research | Date: 2017-04-19

Disclosed are yeast expression constructs encoding a polypeptide containing a signal sequence, a Gol gi -di recti ng pro sequence, and a human amyloid beta protein, and mammalian expression constructs encoding a polypeptide containing a selected signal sequence and a human amyloid beta protein. Also disclosed are methods of screening cells to identify compounds that prevent or suppress amyloid beta-induced toxicity and genetic suppressors or enhancers of amyloid beta-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimers disease.


Patent
Whitehead Institute For Biomedical Research | Date: 2017-03-08

The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of SLC38A9 (NCBI Gene ID: 153129), as well as to the use of such identified compounds in the modulation of mTORC1 and the treatment of diseases and conditions characterized by aberrant mTORC1 activity.


Pattabiraman D.R.,Whitehead Institute For Biomedical Research | Weinberg R.A.,Massachusetts Institute of Technology
Nature Reviews Drug Discovery | Year: 2014

Since their identification in 1994, cancer stem cells (CSCs) have been objects of intensive study. Their properties and mechanisms of formation have become a major focus of current cancer research, in part because of their enhanced ability to initiate and drive tumour growth and their intrinsic resistance to conventional therapeutics. The discovery that activation of the epithelial-to-mesenchymal transition (EMT) programme in carcinoma cells can give rise to cells with stem-like properties has provided one possible mechanism explaining how CSCs arise and presents a possible avenue for their therapeutic manipulation. Here we address recent developments in CSC research, focusing on carcinomas that are able to undergo EMT. We discuss the signalling pathways that create these cells, cell-intrinsic mechanisms that could be exploited for selective elimination or induction of their differentiation, and the role of the tumour microenvironment in sustaining them. Finally, we propose ways to use our current knowledge of the complex biology of CSCs to design novel therapies to eliminate them. © 2014 Macmillan Publishers Limited.


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.


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.


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.

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