University of South Florida

The State University of New York

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Syracuse University

William Garrow Kerr

Caroline Desponts

John D Chisholm

Lia Elena Perez

Sandra Fernandes Denney

Joseph Wahle

Jia-Wang Wang

Frank A Middleton

John Ninos

Matthew Gumbleton

Joseph M McKinley

Sonia Iyer

Sandra Fernandes

The present disclosure provides compositions that inhibit the SH2-containing inositol 5′phosphatase (SHIP) as well as methods using such composition for use in treating or ameliorating the effects of a medical condition in a subject. For examples, compositions including the general formula as disclosed herein are suitable for use herein.

Selective ship inhibitors for treating disease

The present invention relates to SHIP inhibitor compounds and methods for using these compounds. In particular, the present invention discloses the following methods: (i) a method of treating graft versus host disease in a subject; (ii) a method of inhibiting a SHIP1 protein in a cell; (iii) a method of selectively inhibiting a SHIP1 protein in a cell; (iv) a method for treating or preventing graft-versus-host disease (GVHD) in a recipient of an organ or tissue transplant; (v) a method of modulating SHIP activity in a cell expressing SHIP1 or SHIP2; (vi) a method of ex vivo or in vitro treatment of transplants; (vii) a method of inhibiting tumor growth and metastasis in a subject; (viii) a method of treating a hematologic malignancy in a subject; (ix) a method of inducing apoptosis of multiple myeloma cells; (x) a method of treating multiple myeloma in a subject; (xi) a method of inhibiting the proliferation of a human breast cancer cell; and (xii) a method of treating breast cancer in a subject.

Ship inhibitors and uses thereof

The present invention relates to methods and kits for detecting a fusion mRNA transcript or polypeptide encoded by the fusion mRNA transcript. The method includes obtaining a biological sample from a subject and providing one or more reagents capable of binding a fusion mRNA transcript or polypeptide encoded by the fusion mRNA transcript, wherein the fusion mRNA transcript or polypeptide encoded by the fusion mRNA transcript comprises the 3' end of ex on 25 of INPP5D fused to the 5&#x2032; end of ex on 2 of ATG16L1 or the polypeptide encoded by the 3&#x2032; end of ex on 25 of INPP5D fused to the 5&#x2032; end of ex on 2 of ATG16L1, respectively.

Methods and kits for detecting a fusion messenger RNA transcript or a polypeptide encoded by the fusion messenger RNA transcript

The present disclosure provides compositions that inhibit the SH2-containing inositol 5'-phosphatase (SHIP), as well as methods using such compositions for use in treating or ameliorating the effects of a medical condition in a subject.

Tryptamine-based ship inhibitors for the treatment of cancer

The present invention relates to the use of SHIP1 inhibitors and pan-SHIP1/2 inhibitors in various methods, including, without limitation, a method of inhibiting SHIP to induce broad activation of natural killer (NK) cells to treat various diseases.

Ship inhibition to induce activation of natural killer cells

A method of treating or preventing an immune disorder, such as graft versus host disease, in a subject. The method includes the administering a SHIP1 inhibitor, such as 3&#x3b1;-aminocholestane, to a subject in need of treatment. Thus, SHIP1 inhibitors taught herein represent a novel class of small molecules that have the potential to enhance allogeneic transplantation, boost innate immunity and improve the treatment of hematologic malignancies.

Method of modulating ship activity

The subject invention pertains to a method of detecting colon disorders including inflammatory bowel disease, such as Crohn's disease and ulcerative colitis, based on underexpression of Lipopolysaccharide Responsive Beige-like Anchor (LRBA). Advantageously, the invention may be used to test for inflammatory bowel disease using a blood sample from a subject before a more invasive test for colon disorders is employed. The invention also pertains to methods of treating a colon disorder in a subject in which the colon disorder is detected.

Methods of detecting and treating colon disorders

The present invention provides a method of mediating hypo-activation of NK cells. Methods of the present invention comprise administering to a subject an effective amount of broad acting phosphotase inhibitor, such as sodium orthovanadate, SHP specific inhibitor. In one embodiment, the SHP specific inhibitor is NSC119910.

Method of activating NK cells

Inhibition of dendritic cell function in solid organ grafts or allogeneic bone marrow transplants prior to or during engraftment by blocking SH2-containing inositol phosphatase (SHIP) expression or function is taught as a method of abrogating immune rejection and thereby increasing the efficacy of engraftment of an allogeneic bone marrow transplant or solid organ allograft or xenograft. Also disclosed is a transgenic mouse having the genotype SHIPwhich exhibits enhanced survival following mismatched allogeneic marrow grafts.

Reduction of graft-versus-host disease by modulation of SHIP activity

The invention concerns a method for increasing megakaryocyte and megakaryocyte progenitor numbers in vitro or in vivo by suppressing SH2-containing inositol-5-phosphatase (SHIP) function in megakaryocytes or megakaryocyte progenitors expressing the SHIP gene. SHIP function can be suppressed by administering an interfering RNA, or other SHIP inhibitor, to the megakaryocytes or megakaryocyte progenitors in vitro or in vivo.

SHIP-deficiency to increase megakaryocyte progenitor production

A method of increasing megakaryocytes and platelet numbers in a patient comprising the step of inhibiting SHIP expression, including SHIP's enzymatic activity and signaling functions, whereby normal blood clotting is induced.

Control of NK cell function and survival by modulation of SHIP activity

The present invention relates to a novel LPS-responsive and Beige-like Anchor gene (lrba), variants of the lrba gene, fragments of the lrba gene, and polypeptides encoded thereby. The subject invention also pertains to lrba interfering RNA, and uses thereof. In another aspect, the present invention also includes methods of inhibiting tumor growth in a patient by suppressing lrba function.

Growing community of inventors

Syracuse, NY, United States of America

William Garrow Kerr