Abstract: In some aspects, the disclosure provides methods of modulating the level of proteasome inhibitor resistance of a cell, the methods comprising manipulating the level of expression or activity of a subunit of the 19S proteasome in the cell. In some aspects, cells in which the level of a 19S subunit is modulated, e.g., reduced, are provided. In some aspects, methods of identifying agents that reduce proteasome inhibitor resistance are provided. In some aspects, methods of classifying cancers according to predicted proteasome inhibitor resistance are provided. In some aspects, methods of killing or inhibiting proliferation of cancer cells, e.g., proteasome inhibitor resistant cancer cells, are provided. In some aspects, methods of treating cancer, e.g., proteasome inhibitor resistant cancer, are provided.

Abstract: A method for treating neurodegenerative disease in a subject in need thereof by administering to the subject an effective amount of a Nedd4 activator as described herein.

Abstract: Disclosed are methods, systems, cells and compositions directed to modeling a physiologic or pathologic process in an animal using a set of yeast genes analogous to a set of animal genes and augmenting the physiologic or pathologic process in the animal with predicted gene interactions based on the interactions between the set of yeast genes. Also disclosed are methods of screening for and using therapeutics for neurodegenerative proteinopathies.

Abstract: It has been established that exposure to cytotoxic doses of HSP90 inhibitor is broadly immunosuppressive, whereas continuous exposure to low-dosages of the same inhibitor exerts anti-tumor activity. The anti-tumor activity is mediated by the host immune system. Compositions and methods for continuous, low-dose exposure to HSP90 inhibitors in combination with one or more immunostimulatory agents for the treatment of cancer are described. Typically, the HSP90 inhibitor is administered in an amount that is between 1% and 20% of the clinically-determined maximum tolerate dose. The immunostimulatory agent can be administered simultaneously with the HSP90 inhibitor, or at some time before or after the HSP90 inhibitor. Compositions including a sub-toxic dose of HSP90 inhibitor in combination with an immunostimulatory agent in an amount effective to treat cancer are also provided.

Abstract: In some aspects, the disclosure provides methods of modulating the level of proteasome inhibitor resistance of a cell, the methods comprising manipulating the level of expression or activity of a subunit of the 19S proteasome in the cell. In some aspects, cells in which the level of a 19S subunit is modulated, e.g., reduced, are provided. In some aspects, methods of identifying agents that reduce proteasome inhibitor resistance are provided. In some aspects, methods of classifying cancers according to predicted proteasome inhibitor resistance are provided. In some aspects, methods of killing or inhibiting proliferation of cancer cells, e.g., proteasome inhibitor resistant cancer cells, are provided. In some aspects, methods of treating cancer, e.g., proteasome inhibitor resistant cancer, are provided.

Abstract: In some aspects, the disclosure provides methods of modulating the level of proteasome inhibitor resistance of a cell, the methods comprising manipulating the level of expression or activity of a subunit of the 19S proteasome in the cell. In some aspects, cells in which the level of a 19S subunit is modulated, e.g., reduced, are provided. In some aspects, methods of identifying agents that reduce proteasome inhibitor resistance are provided. In some aspects, methods of classifying cancers according to predicted proteasome inhibitor resistance are provided. In some aspects, methods of killing or inhibiting proliferation of cancer cells, e.g., proteasome inhibitor resistant cancer cells, are provided. In some aspects, methods of treating cancer, e.g., proteasome inhibitor resistant cancer, are provided.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: In some aspects, the invention provides methods of identifying, detecting, and/or measuring protein-protein interactions. In some aspects, the invention provides methods of identifying and/or characterizing modulators of protein-protein interactions. In some aspects, the invention provides methods of identifying and/or characterizing modulators of protein activity, wherein the methods are based at least in part on measuring interaction between a chaperone and client protein. In some aspects, the invention provides methods for identifying and/or characterizing compounds and/or for assessing compound specificity, wherein the methods are based at least in part on measuring interaction between a chaperone and client protein. In some embodiments, a client protein is a kinase. In some embodiments, a compound is a kinase inhibitor. In some aspects, the invention provides methods of profiling kinase inhibitor specificity.

Abstract: In some aspects, the invention relates to Heat Shock Protein-1 (HSF1) gene and HSF1 gene products. In some aspects, the invention provides methods of tumor diagnosis, prognosis, treatment-specific prediction, or treatment selection, the methods comprising assessing the level of HSF1 expression or HSF1 activation in a sample obtained from the tumor. In some aspects, the invention relates to the discovery that increased HSF1 expression and increased HSF1 activation correlate with poor outcome in cancer, e.g., breast cancer.

Abstract: In some aspects, the invention relates to Heat Shock Protein-1 (HSF1) gene and HSF1 gene products in tumor stroma. In some aspects, the invention provides methods of tumor prognosis, treatment-specific prediction, or treatment selection, the methods comprising measuring the level of HSF1 expression or HSF1 activation in a sample obtained from the tumor that comprises tumor-associated stromal cells. In some aspects, the invention relates to the discovery that increased HSF1 expression and increased HSF1 activation in tumor-associated stromal cells correlate with poor outcome in cancer. In some embodiments, the methods comprise measuring HSF1 expression or activation specifically in tumor-associated stromal cells. In some embodiments, the methods comprise measuring HSF1 expression or activation specifically in tumor-associated stromal cells and specifically in cancer cells. In some embodiments HSF1 expression or activation is measured using an antibody that specifically binds to HSF1.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: In some aspects, the invention relates to Heat Shock Protein-1 (HSF1) gene and HSF1 gene products. In some aspects, the invention provides methods of tumor diagnosis, prognosis, treatment-specific prediction, or treatment selection, the methods comprising assessing the level of HSF1 expression or HSF1 activation in a sample obtained from the tumor. In some aspects, the invention relates to the discovery that increased HSF1 expression and increased HSF1 activation correlate with poor outcome in cancer, e.g., breast cancer. In some aspects, the invention relates to the HSF1 cancer program genes, HSF1 cancer signature set genes, subsets thereof, and uses in tumor diagnosis, prognosis, treatment-specific prediction, treatment selection, or drug discovery, among others.

Abstract: In some aspects, the invention provides methods of identifying, detecting, and/or measuring protein-protein interactions. In some aspects, the invention provides methods of identifying and/or characterizing modulators of protein-protein interactions. In some aspects, the invention provides methods of identifying and/or characterizing modulators of protein activity, wherein the methods are based at least in part on measuring interaction between a chaperone and client protein. In some aspects, the invention provides methods for identifying and/or characterizing compounds and/or for assessing compound specificity, wherein the methods are based at least in part on measuring interaction between a chaperone and client protein. In some embodiments, a client protein is a kinase. In some embodiments, a compound is a kinase inhibitor. In some aspects, the invention provides methods of profiling kinase inhibitor specificity.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: In some aspects, the invention relates to Heat Shock Protein-1 (HSF1) gene and HSF1 gene products. In some aspects, the invention provides methods of tumor diagnosis, prognosis, treatment-specific prediction, or treatment selection, the methods comprising assessing the level of HSF1 expression or HSF1 activation in a sample obtained from the tumor. In some aspects, the invention relates to the discovery that increased HSF1 expression and increased HSF1 activation correlate with poor outcome in cancer, e.g., breast cancer.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: The present invention generally relates to engineered bacteriophages which express amyloid peptides for the modulation (e.g. increase or decrease) of protein aggregates and amyloid formation. In some embodiments, the engineered bacteriophages express anti-amyloid peptides for inhibiting protein aggregation and amyloid formation, which can be useful in the treatment and prevention of and bacterial infections and biofilms. In some embodiments, the engineered bacteriophages express amyloid peptides for promoting amyloid formation, which are useful for increasing amyloid formation such as promoting bacterial biofilms. Other aspects relate to methods to inhibit bacteria biofilms, and methods for the treatment of amyloid related disorders, e.g., Alzheimer's disease using an anti-amyloid peptide engineered bacteriophages. Other aspects of the invention relate to engineered bacteriophages to express the amyloid peptides on the bacteriophage surface and/or secrete the amyloid peptides, e.g.

Abstract: Using arrays of peptides derived from E. coli CsgB, peptides that seed formation of curli fibers are identified. The arrays, peptides, methods for identification thereof, and compositions and methods relating thereto, are provided.

Abstract: The present invention provides a yeast cell based system for determining factors that control the folding of amyloid proteins of diverse origins. Further the present invention provides methods of using such a system to screen for reagents that affect amyloid formation, a process that is integral to several devastating human disease including Creutzfeld-Jacob disease (CJD), fatal familial insomnia (FFI), Gertsmann-Straussler-Scheinker (GSS) syndrome, and kuru. The system of the present invention provides a rapid screening system to quickly and cheaply identify reagents that affect the folding and aggregation properties of the target protein.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.