Barry M Henderson

US Patent:

20060234242, Oct 19, 2006

Filed:

Apr 7, 2004

Appl. No.:

10/552642

Inventors:

Richard Cheatham - Durham NC, US
Barry Henderson - Hillsborough NC, US
William Phelps - Durham NC, US

Assignee:

Ribonomics, Inc. - Durham NC

International Classification:

C12Q 1/68

US Classification:

435006000

Abstract:

The identification and evaluation of mRNA and protein targets associated with RNA binding proteins or mRNP complexes is described. In particular, the invention provides methods for identifying RNA binding proteins associated with physiological pathways that participate in glucose and lipid metabolism and mRNAs that exhibit coordinated gene regulation across those M pathways. Candidate targets are provided that are useful for the diagnosis or treatment of diseases related to diseases, such as disease related to aberrant glucose and lipid metabolism, such as, for example, obesity, diabetes, and hypoglycemia.

US Patent:

20060275816, Dec 7, 2006

Filed:

Jun 5, 2006

Appl. No.:

11/446864

Inventors:

Barry Henderson - Hillsborough NC, US
Richard Cheatham - Durham NC, US

Assignee:

Ribonomics, Inc. - Durham NC

International Classification:

C12Q 1/68

US Classification:

435006000

Abstract:

The invention combines a microarray and cell-based screening strategy that enables rapid identification of possible mechanisms underpinning the pharmacology and toxicology of drug candidates. The methods of the invention identified unique properties relating to apoptosis and the anti-inflammatory response elicited by several peroxisome proliferator activated receptor gamma (PPARγ) ligands. The methods illustrate, for example, that PPARγ ligands that are safe and effective drugs (e.g., Actos, Avandia) either do not induce apoptosis or only modestly induce apoptosis. Conversely, PPARγ ligands that have failed clinical development (e.g., Ciglitazone; Day, C., Diabet. Med., 16: 179-192 (1999)) or that have been withdrawn from the market (e.g., Troglitazone (Rezulin)) due to hepatotoxicity are potent inducers of apoptosis. The methods of the invention also illustrate that suppression of gene expression and protein expression for several pro-inflammatory factors by some PPARγ ligands occurs as a consequence of apoptotic induction (i.e., apoptosis produces an anti-inflammatory response). The invention also provides biomarkers for cellular pathways and methods for stratifying patient groups according to their biomarker expression as well as biomarkers that discriminate safe and effective drugs from compounds that have acute toxicities. These biomarkers provide novel insights into the mechanism of action and toxicity for test compounds, including cell death, anti-inflammatory activity, hepatotoxicity, and carcinogenicity. The methods are highly scalable and have broad application from discovery to the clinic, including compound prioritization, predictive pharmacology and toxicology; mechanism of action studies; and prognostic and diagnostic biomarker discovery.