Tufts University

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Duke University

The University of North Carolina at Chapel Hill

Musc Foundation for Research Development

Bryan P Toole

Suniti Misra

Shibnath Ghatak

Jian Liu

Stavros Garantziotis

John W Hollingsworth

Brent Cochran

Aliki Grammatikakis

Nicholas Grammatikakis

Shib D Banerjee

Described herein is the finding that hyaluronan antagonists that inhibit hyaluronan signaling are capable of inhibiting airway inflammation and airway hyperresponsiveness (AHR). The present disclosure provides a method of preventing or reducing AHR in a subject suffering from or at risk for AHR by administering a hyaluronan antagonist. Also provided is a method of treating an airway disease or disorder in a subject by administering a hyaluronan antagonist. Hyaluronan antagonists include, for example, heparosan and hyaluronan oligosaccharides (oHAs). In some embodiments, the hyaluronan antagonist is administered locally to the airway, such as with an inhaler or nebulizer.

Uses of antagonists of hyaluronan signaling

Pharmaceutical compositions and methods for sensitizing multi-drug resistant cancer or radiation resistant cancer cells to chemotherapeutic agents are provided. Compositions include ligands of hyaluronan receptors, including glycosaminoglycans such as hyaluronan oligomers and derivatives of these oligomers, hyaluronan binding proteins, antibodies specific for hyaluronan receptors, hyaluronan mimetics, inhibitors of hyaluronan synthesis, and stimulators of hyaluronan degradation.

Methods and compositions for inhibition of multi-drug resistance by hyaluronan oligomers

Disclosed are substantially pure nucleic acid sequences encoding vertebrate cdc37. The protein encoded by this nucleic acid is characterized by the ability to bind specifically to mammalian proteins selected from the group consisting of cdk4, cyclin D, cdk2, Rb, hsp90, hsp60, hsp70, Raf-1, MEK-1, SAPK, MAPK, ERK1, P13-K and the src family of tyrosine kinases. In addition, the protein is further characterized by the ability to bind glycosaminoglycan. Also disclosed are diagnostic and therapeutic applications based on the isolation of the nucleic acid sequences.

Nucleic acid encoding vertebrate cdc37

Hyaluronan-binding protein (HABP) is expressed on the cell surface during tumor cell and endothelial cell migration and during capillary-like tubule formation. Monoclonal antibodies and hyaluronan oligosaccharides are described which specifically recognize HABP and can be used to (1) inhibit tumor growth by preventing tumor vascularization, (2) inhibit tumor cell migration and (3) image tumors.

Oligosaccharides reactive with hyaluronan-binding protein and their

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Mt. Pleasant, SC, United States of America

Bryan P Toole