The Johns Hopkins University

Leland Stanford Junior University

University of Washington

Other

Baylor College of Medicine

Children's Hospital & Research Center Oakland

Philip Arden Beachy

Jeffrey A Porter

James K Chen

Michael K Cooper

Randall Todd Moon

Anssi Jussi Nikolai Taipale

Ming-Jer Tsai

Venkatesh Krishnan

Sophia Yang Tsai

Chien-Huan Chen

Anssi J Taipale

Jayakumar Rajadas

Jun O Liu

Ervin H Epstein, Jr

Jean Tang

Jeffery Porter

Edda Spiekerkoetter

Marlene Rabinovitch

Jefferey A Porter

Jynho Kim

Ronald K Mann

David Solow-Cordero

Jussi Taipale

Kunyoo Shin

James Kim

Jun Liu

Methods for treating cancer by activation of the Bmp pathway are disclosed. In particular, the invention relates to methods of treating cancer using agents that activate BMP signaling, e.g., FK506 (tacrolimus), to treat a subject for cancer.

Methods for treating cancer by activation of BMP signaling

A method of reducing pulmonary arterial hypertension in a mammal that employs FK506 is provided. In certain embodiments, the method comprises administering FK506 to a mammal having pulmonary arterial hypertension associated with defective MBPR2 signaling at a dosage sufficient to reduce blood pressure in the pulmonary artery of the mammal.

Use of FK506 for the treatment of pulmonary arterial hypertension

The present invention makes available, inter alia, methods and reagents for modulating smoothened-dependent pathway activation. In certain embodiments, the subject methods can be used to counteract the phenotypic effects of unwanted activation of a hedgehog pathway, such as resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function mutations.

Regulators of the hedgehog pathway, compositions and uses related thereto

The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein or aberrant activation of a hedgehog signal transduction pathway, e.g., which involve the use of a steroidal alkaloid or other small molecule.

Inhibitors of hedgehog signaling pathways, compositions and uses related thereto

Methods of transdermally delivering a therapeutic amount of a triazole-triazolone compound are provided, e.g. for the prevention or treatment of basal cell carcinoma (BCC) in a subject. A therapeutic level of a triazole-triazolone compound such as itraconazole is delivered transdermally to a subject. Also provided are topical triazole-triazolone compositions that find use in practicing the subject methods.

Topical itraconazole formulations and uses thereof

Compounds, compositions, kits and methods for modulating hedgehog pathway activity, and treating conditions related to abnormal or aberrant hedgehog pathway activity, are disclosed.

Hedgehog pathway antagonists to treat disease

The present invention provides two novel polypeptides, referred to as the 'N' and 'C' fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G'CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.

Method of detection using antibodies that specifically bind hedgehog-derived polypeptides

The present invention makes available assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein or aberrant activation of a hedgehog signal transduction pathway, e.g., which involve the use of a steroidal alkaloid or other small molecule.

The present invention sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described. In one aspect of the invention, the method provides a means for affecting cholesterol biosynthesis or transport in a cell comprising contacting a cell with an effective amount of a compound that affects hedgehog, thereby affecting cholesterol biosynthesis or transport. The effect may be inhibition or stimulation of cholesterol biosynthesis or transport.

Cholesterol and hedgehog signaling

Antibodies that specifically bind hedgehog-derived polypeptides

Aromatic compounds for treating various diseases and pathologies are disclosed. The methods use of such compounds are also provided. Accordingly, the present invention makes available methods and compositions for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function.

Hedgehog pathway antagonists

Elevated Hedgehog (Hh) pathway activity, including ligand stimulated Hh pathway activity, was detected in hematopoietic malignancy cells, and determined to be associated with growth and proliferation of the malignancy cells. Accordingly, methods are provided for treating a hematopoietic cell malignancy associated with elevated Hh pathway activity by reducing or inhibiting the Hh pathway activity. Also provided are methods of determining the responsiveness of a hematopoietic cell malignancy to treatment with an Hh pathway antagonist.

Compounds for hedgehog pathway blockade in proliferative disorders, including hematopoietic malignancies

The present invention provides transcription factors associated with the hedgehog signaling pathway that are regulated by dephosphorylation by phosphatases. Hedgehog response elements (HRE) that interact with the dephosphorylated transcription factors are also provided as well as methods for identifying compounds that are phosphatase inhibitors. Methods of treating tumors in a subject by modulating the phosphorylation of the transcription factor are also included.

Growing community of inventors

Stanford, CA, United States of America

Philip Arden Beachy