Whitehead Institute for Biomedical Research

Albert Einstein College of Medicine

Other

Leland Stanford Junior University

Massachusetts Institute of Technology

Dana-farber-cancer Institute Inc.

The Beth Israel Hospital Association

Beth Israel Hospital

Whitehead Institute for Biomedical Research Dana-farber Cancer Institute, Inc.

Richard A Young

Anna Aldovini

Ronald W Davis

Barry R Bloom

William R Jacobs, Jr

Robert N Husson

David M Chao

Craig M Thompson

Anthony J Koleske

Rudolf Jaenisch

Alexander Marson

Peter B Rahl

Ruth Foreman

Bing Ren

Brett Chevalier

Tong Ihn Lee

John Wyrick

James Elliott Bradner

Herman N Eisen

David Baltimore

Jianzhu Chen

Michael A O'Donnell

Didier Trono

Mark B Feinberg

William C DeWolf

Itamar Simon

Qian Huang

Joan F L Richmond

Bryan K Cho

Rosemary B Duda

Abraham S Weintraub

Francois Robert

Brian J Abraham

Denes Hnisz

Jun Qi

Jason J Marineau

Michael Robert McKeown

Dmitry K Pokholok

Tan A Ince

Douglas B Young

David A Orlando

Ernest Fraenkel

Matthew G Guenther

David M Truong

Deborah Palliser

Brian Abraham

Alla A Sigova

Jurian Schuijers

Robert Francois

John C Manteiga

Charles H Li

Michael F Drzewiecki

Ellen L Gadbois

Frank C P Holstege

Deborah Pallister

David B Gordon

Christopher T Harbison

Tom Y Wang

Tony Lee

Charles Y Lin

Heather Hoke

Jakob Loven

Warren Whyte

Zi Peng Fan

Violaine Saint-Andre

James E Bradner

Michael R Mckeown

François Robert

Disclosed are methods of altering expression of a gene with a promoter region CTCF binding site. Also disclosed are compositions and methods useful for treating a disease or condition involving over-expression or under-expression of a gene with a promoter region CTCF binding site. Further disclosed are cells and non-human animals with modified a promoter region CTCF binding site, as well as methods for screening for compounds that can modify the expression of a gene with a promoter region CTCF binding site.

Regulation of transcription through CTCF loop anchors

The invention relates to methods of modulating the expression of one or more genes in a cell by modulating the multimerization of a transcription factor and/or modulating the formation of enhancer-promoter DNA loops, and thereby modulating the expression of the one or more genes. The invention also relates to treating diseases and conditions involving aberrant gene expression by modulating the multimerization of a transcription factor and/or modulating the formation of enhancer-promoter DNA loops. The invention also relates to methods for screening for compounds that modulate expression of one or more genes in a cell.

Methods of altering gene expression by perturbing transcription factor multimers that structure regulatory loops

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.

Wnt pathway stimulation in reprogramming somatic cells with nuclear reprogramming factors

Disclosed are methods for identifying the core regulatory circuitry or cell identity program of a cell or tissue, and related methods of diagnoses, screening, and treatment involving the core regulatory circuitry and/or cell identity programs identified using the methods.

Core transcriptional circuitry in human cells and methods of use thereof

The present invention relates in some aspects to super-enhancers and related compositions, methods, and agents that are useful for modulating expression of cell type-specific genes that are required for maintenance of cell identity (e.g., embryonic stem cell identity) or maintenance of a disease state (e.g., cancer).

Super-enhancers and methods of use thereof

Disclosed herein are methods and compositions useful for inhibiting interaction between a bromodomain protein and an immunoglobulin (Ig) regulatory element. The methods and compositions are particularly useful for downregulating expression of an oncogene translocated with an Ig locus, as well as for treating a cancer (e.g., hematological malignancy) characterized by increased expression of an oncogene which is translocated with an Ig locus. Also disclosed herein are methods and assays for identifying agents that interfere with binding of bromodomain proteins to Ig regulatory elements, as well as methods and assays for identifying inhibitors of bromodomain.

Method for identifying bromodomain inhibitors

The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors. 

Pyrrol-1-yl benzoic acid derivatives useful as myc inhibitors

In some aspects, the invention provides compositions and methods of use for treating a variety of diseases. In some aspect, the compositions and methods involve combined modulation of transcriptional modulators.

Combination methods for treatment of disease

WNT pathway stimulation in reprogramming somatic cells with nuclear reprogramming factors

The invention provides methods of targeting tumor stem cells that comprise inhibiting the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. The invention further provides methods for identifying tumor stem cells comprising detecting increased levels and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. Further provided are kits and articles of manufacture comprising inhibitors of the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. Methods for screening for inhibitors of the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7 are also provided.

Markers for and methods of targeting tumor stem cells

A medication container with a Fresnel lens formed on its surface is described. The Fresnel lens provides a magnified view of the medication content of the container so that a user such as a pharmacist or a patient can accurately determine the medication content without opening the container. In one embodiment, the medication container is generally cylindrical in shape and a Fresnel lens is formed on the bottom of the container. In other embodiments, the Fresnel lens is formed on the cap of a middle component located between the cap and the body of the container.

Medication container with Fresnel lens

The invention relates to the identification of biologically-active DNA-binding sites to which a protein of interest binds in a cell. The invention also relates to the identification of agents and conditions which alter the biologically-active DNA-binding sites to which a protein binds. One aspect of the invention also provides methods for identifying pathways that are regulated by transcriptional regulators and for modulating the activity of the pathways.

Biologically-active DNA-binding sites and related methods

The present invention relates to a method of identifying a region (one or more) of a genome of a cell to which a protein of interest binds. In the methods described herein, DNA binding protein of a cell is linked (e.g., covalently crosslinked) to genomic DNA of a cell. The genomic DNA to which the DNA binding protein is linked is removed and combined or contacted with DNA comprising a sequence complementary to genomic DNA of the cell under conditions in which hybridization between the identified genomic DNA and the sequence complementary to genomic DNA occurs. Region(s) of hybridization are region(s) of the genome of the cell to which the protein of binds. A method of identifying a set of genes where cell cycle regulator binding correlates with gene expression and of identifying genomic targets of cell cycle transcription activators in living cells is also encompassed.

Genome wide location and function of DNA binding proteins

Growing community of inventors

Weston, MA, United States of America

Richard A Young