Harvard College

Cornell University

Dana-farber-cancer Institute Inc.

Other

University System of Maryland

Genetics Institute, Inc.

Compagnie Gervais Danone

Repligen Corporation

Laurie H Glimcher

Gordon James Freeman

Lee M Nadler

Suzanne Ostrand-Rosenberg

I-Cheng Ho

Juan Rodrigo Cubillos-Ruiz

Susanne J Szabo

Sarah Bettigole

Martin R Hodge

Sivasubramanian Baskar

Dallas C Jones

John Douhan, Iii

Joseph P Vacca

Wendy Sarah Garrett

Marc Wein

Andreas M Reimold

Ann-Hwee Lee

Hong Zhou

Isabelle Chambaud

Eun Sook Hwang

Artem Khlebnikov

Patrick Veiga

Mohamed Oukka

Ann M Ranger

Juan Rodrigo Cubillos Ruiz

Antonios O Aliprantis

Han Dong

Mahesh Raundhal

Xi Chen

Fabio Martinon

Sivasubramanina Baskar

The present invention relates, in part, to methods for treating red blood cell disorders, such as an MDS and/or an anemia, by down-regulating IL-22 signaling.

Methods of treating anemia in myelodysplastic syndromes

The present invention is based, in part, on the identification of an IRE1α-XBP1-cMyc axis in NK cell immunity. The present invention provides compositions and methods for treating conditions that would benefit from modulating (e.g., upregulating or downregulating) an immune response using an agent that modulates the IRE1α-XBP1 pathway, or a composition comprising modified NK cells.

Use of IRE1α-XBP1 signaling pathway biomarkers for modulating immune responses

Described herein are IRE1&#x3b1; inhibitors, compositions containing such inhibitors, and methods of treatment that include administration of such compounds. Exemplary compounds are provided throughout the application.

Small molecule IRE1-&#x3b1; inhibitors

Described herein is a previously unknown function of XBP1 in triple-negative breast cancer (TNBC). It is shown that XBP1 is preferentially spliced and activated in TNBC, and that deletion of XBP1 significantly blocks triple negative breast tumor growth. Strikingly, XBP1 is required for the self-renewal of breast tumor initiating cells (TICs). Genome-wide mapping of the XBP1 transcriptional regulatory network identified a fundamental role for XBP1 in regulating the response to hypoxia via the transcription factor hypoxia-inducible factor 1&#x3b1; (HIF1&#x3b1;). Importantly, activation of this pathway appears to carry prognostic implications, as expression of the XBP1-dependent signature is associated with shorter survival times in human TNBC.

Modulation of breast cancer growth by modulation of XBP1 activity

Described herein is a previously unknown function of XBP1 in controlling anti-tumor immunity. It is shown that inhibiting XBP1 in tumor-associated dendritic cells inhibits tumor growth and induces protective anti-tumor immune responses.

Compounds for inducing anti-tumor immunity and methods thereof

The invention provides, e.g., compositions and methods for increasing activation of immune cells.

Methods for increasing immune responses using agents that directly bind to and activate IRE-1

This invention is based, at least in part, on the discovery that Shn2 and Shn3 play an important role in skeletal remodeling and skeletal patterning. Accordingly, the present invention provides methods for identifying medulators of Shn2 activity and methods for modulating bone formation and mineralization and Shn2-associated disorders using agents that modulate Shn2 expression and/or activity, in addition to methods for modulating Shn2 and Shn3.

Methods for modulating skeletal remodeling and patterning by modulating SHN2 activity, SHN3 activity, or SHN2 and SHN3 activity in combination

The invention provides methods and compositions for modulating the expression, processing, post-translational modification, stability and/or activity of XBP-1 protein, or a protein in a signal transduction pathway involving XBP-I to treat dyslipidemias and steatosis disorders. The present invention also pertains to methods for identifying compounds that modulate the expression, processing, post-translational modification, and/or activity of XBP-I protein or a molecule in a signal transduction pathway involving XBP-1.

Methods for modulating de novo hepatic lipogenesis by modulating XBP-1 activity

The present invention relates to a method for the prevention, treatment and reduction of gastro-intestinal inflammation in a subject by administering a specificbacteria, in particular a fermented dairy product comprising said specificbacteria for the prevention, treatment and reduction of gastro-intestinal inflammation, in particular for the prevention and treatment of inflammatory bowel disease (IBD), ulcerative colitis (UC) and/or Crohn's Disease (CD) and for the prevention and treatment of Irritable Bowel Syndrome (IBS).

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The instant invention is based, at least in part, on the discovery that T-bet maintains host commensal relationships in the gastrointestinal tract. Accordingly, this invention provides methods of treating and/or preventing ulcerative colitis, and/or colon cancer, and/or preventing colonization of a subject's gastrointestinal tract with commensal bacteria that promote ulcerative colitis as well as methods of identifying agents that treat and prevent the same.

Compositions and methods for the treatment and prevention of ulcerative colitis and colon cancer and screening methods to identify same

The present invention is based, at least in part, on the identification of molecules involved in the differentiation and/or activity of osteoblasts and osteoclasts. Accordingly, the present invention provides methods of identifying modulators of bone formation, mineralization, and/or osteoclastogenesis and methods for treating disorders that would benefit from modulation of bone formation, mineralization, and/or osteoclastogenesis using agents identified as described herein.

Molecules involved in regulation of osteoblast activity and osteoclast activity, and methods of use thereof

The instant invention is based, at least in part, on the discovery that T-bet controls ThI cell recruitment to sites of inflammation. This invention pertains to, inter alia, methods of identifying agents that modulate the effects of T-bet on the recruitment of T cells to sites of inflammation by modulating P-selectin-mediated T cell rolling and/or stable adherence of a T cell to a vascular endothelial cell, as well as methods of use therefore.

Modulation of T cell recruitment

Growing community of inventors

West Newton, MA, United States of America

Laurie H Glimcher