Bristol-Myers Squibb Compnay

Leah Ann Garulacan

Gregory Opiteck

John N Feder

Chandra S Ramanathan

Gena S Whitney

Murray McKinnon

Frederic Moulin

Stephen K Durham

Stanley Hefta

Ji Gao

Stephen M Storm

Jun-Hsiang Lin

Donna Dambach

The present invention describes a G-protein coupled receptor (GPCR) family member newly identified as being modified, e.g., phosphorylated, and associated with tyrosine phosphorylated activation complexes, following exposure of cells to smoke from tobacco burning substances, namely, cigarette smoke. This GPCR protein is RAI-3, which was first found to be phosphorylated in cells treated with cigarette smoke and to be associated with other proteins activated in cigarette smoke treated cells by virtue of the present invention. Because cigarette smoke is considered to be a major causative factor of chronic obstructive pulmonary disease (COPD) and disorders and conditions related thereto, the RAI-3 protein is newly provided as a cellular drug target for screening, discovering, and identifying modulators for the treatment and/or prevention of COPD and its related disorders and conditions, such as emphysema and chronic bronchitis. In accordance with the present invention RAI-3 modulators, e.g., agonists and antagonists, can be used as therapeutics in the treatment of COPD and numerous other diseases and disorders that are associated with regulation of NF-&#x3ba;B and/or its associated or interacting signaling molecules. This invention further provides SNPs of RAI-3, e.g., for determining COPD association in individuals.

Methods of diagnosing tumors using the G-protein coupled receptor (GPCR), RAI-3

The present invention relates to biomarker polypeptides, polynucleotides, and antibodies that have utility in predicting in vitro and/or in vivo hepatotoxicity of various drugs, compounds, or other therapeutic agents (i.e., test substances). Also related are screens, kits, microarrays, and cell culture systems that employ the polypeptides, polynucleotides, and/or antibodies of the invention. The reagents and methods of the invention are useful for predicting hepatotoxic effects resulting from treatment with one or more test substances, and can be utilized before, after, or concurrently with pre-clinical, clinical, and/or post-clinical testing. In this way, the reagents and methods of the invention can be used to identify test substances or combinations of test substances that cause hepatic injury, including idiosyncratic hepatotoxicity, and thereby prevent medical complications (e.g., liver failure) resulting from such injury.

Identification of biomarkers for liver toxicity

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King of Prussia, PA, United States of America

Leah Ann Garulacan