Marshall University Research Corporation

The University of Toledo

Zijian Xie

Joseph I Shapiro

Moumita Banerjee

Sandrine V Pierre

Nader G Abraham

Jiang Tian

Xiaoyu Cui

Jiang Liu

Komal Sodhi

Jiayan Wang

Juan Sanabria

Methods for treating non-alcoholic steatohepatitis and/or hepatocellular carcinoma include administering a polypeptide antagonist of a Na/K ATPase/Src receptor complex to a subject in need thereof. Methods and assays for diagnosis or prognosis of non-alcoholic steatohepatitis and/or hepatocellular carcinoma in a subject are also provided and include the steps of providing a biological sample from the subject, determining an expression level or activity in the sample of at least one biomarker selected from Caveolin-1, Survivin, and SMAC; and comparing the expression level or activity of the at least one biomarker in the sample, if present, to a control expression level or activity of the at least one biomarker. Prophylaxis or treatment of the non-alcoholic steatohepatitis and/or hepatocellular carcinoma in a subject can then be initiated based on the expression level or activity of Caveolin-1, Survivin, and SMAC in the sample.

Methods for treatment and diagnosis of non-alcoholic steatohepatitis and/or hepatocellular carcinoma

Methods for treating uremic cardiomyopathy are provided and include the step of administering a polypeptide antagonist of a Na/K ATPase/Src receptor complex to a subject in need thereof. The polypeptide anatagonist can further include a cell penetrating polypeptide. Methods of treating anemia, including anemia-associated with chronic kidney disease, are also provided.

Compositions and methods for treatment of uremic cardiomyopathy

Methods for diagnosis or prognosis of a cancer in a subject are provided and include the steps of: obtaining a biological sample from a subject; determining an amount of a phosphorylation at a Y260 residue in a Na/K ATPase present in the biological sample; and comparing the amount of the phosphorylation in the sample to a control level to thereby diagnose the cancer. Methods for detecting a metabolic switch from oxidative phosphorylation to aerobic glycolysis are also provided in which a biological sample including one or more cells is obtained and an amount of a phosphorylation at a Y260 residue in a Na/K ATPase is determined in the one or more cells.

Methods for detecting Na/K-ATPase-mediated Src signaling for diagnosis and prognosis of cancer

Methods for treating obesity are provided and include administering a polypeptide antagonist of a Na/K ATPase/Src receptor complex to a subject in need thereof. Methods for reducing adiposity and adipogenesis are also provided and make use of a polypeptide antagonist of a Na/K ATPase/Src receptor complex to a subject.

Methods for treating obesity

Methods treating pulmonary hypertension, including pulmonary arterial hypertension, are provided, and include administering a polypeptide antagonist of a Na/K ATPase/Src receptor complex to a subject in need thereof. Administration of the polypeptide antagonist reduces pulmonary artery acceleration time, reduces an amount of right ventricular hypertrophy, reduces right ventricular wall thickness, reduces an amount of pulmonary vessel wall thickness, reduces an amount of plexiform lesions in a lung of the subject, reduces an amount of collagen deposition in a pulmonary blood vessel, reduces an amount of collagen deposition in a pulmonary blood vessel media or adventitia, and/or reduces an amount of right ventricular fibrosis. Methods of reducing pulmonary vessel wall thickness are also provided and include the administration of the polypeptide antagonist of a Na/K ATPase/Src receptor complex.

Compositions and methods for treating pulmonary hypertension

Methods for treating retinopathy are provided and include administering an effective amount of a polypeptide antagovist of a Na/K ATPase/Src receptor complex to a subject. The retinopathy can include diabetic retinopathy. Methods of decreasing angiogenesis in a retinal vasculature are also provided and include the step of administering, such as by intravitreous injection, a polypeptide antagonist of a Na/K ATPase/Src receptor complex to a subject in need thereof.

Compositions and methods for treating retinopathy

Non-naturally occurring peptides are provided that act as a Src SH2 domain antagonist of cardiotonic steroids. Pharmaceutical compositions comprising the peptides are also provided along with vectors encoding the peptides. Methods of treating a Src-associated disease and reducing Src activity in a cell are further provided and include administering or contacting a cell with an effective amount of the peptide.

Cardiotonic steroid antagonists and related methods

This process relates to a pharmaceutical composition of an Na&#x2014;K-ATPase ligand which will stimulate Na/K-ATPase signaling in a pharmaceutically acceptable vehicle. In one embodiment, the composition may be used to treat a skin disorder. In another embodiment, the composition may be used to inhibit cardiac fibrosis.

Na/K-ATPase ligand

A method for regulating Src and its downstream signaling pathway which includes binding between Src and Na+/K+-ATPase is disclosed. The Na+/K+-ATPase/Src complex is a functional receptor for cardiotonic steroids such as ouabain. Also disclosed are Src inhibitors or activators which include either Na+/K+-ATPase or Src that interfere with the interaction between the Na/K-ATPase and Src, act via a different mechanism from ATP analogues, and is pathway (Na+/K+-ATPase) specific.

Growing community of inventors

Huntington, WV, United States of America

Zijian Xie