The Johns Hopkins University

Curis, Inc.

University of Washington

Other

Biogen Idec, Inc.

Jeffrey A Porter

Philip Arden Beachy

Michael K Cooper

Randall Todd Moon

Stephen Colin Price

Edward Andrew Boyd

Lee L Rubin

Oivin M Guicherit

Anthony David Baxter

R Blake Pepinsky

Ellen A Garber

Frederick Robbins Taylor

Kevin P Williams

Dingyi Wen

Darren P Baker

Alphonse Galdes

Russell Colyn Petter

Paul H Weinreb

John Harry Alexander Stibbard

Kathryn Strauch

Chenhui Zeng

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 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

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

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 GCF 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.

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&#x2193;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.

Hedgehog-derived polypeptides

Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.

Hydrophobically-modified protein compositions and methods

Inhibitors of hedgehog signal pathways, compositions and uses related thereto

The present invention makes available methods and reagents for inducing activation of a hedgehog pathway in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as a small molecule, in a sufficient amount to achieve a therapeutic result. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Agonists of hedgehog signaling pathways and uses related thereto

A compound represented in general formula (X) and (XI):

Small organic molecule regulators of cell proliferation

The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. and In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Hydrophobically-modified hedgehog protein compositions and methods

The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein comprising contacting a cell sensitive to the hedgehog protein with a steroidal alkaloid, or other small molecule, in a sufficient amount to reduce the sensitivity of the cell to the hedgehog protein.

Growing community of inventors

Belmont, MA, United States of America

Jeffrey A Porter