Abstract: Methods and compositions are provided for diagnosing ectopic pregnancy in a mammalian subject by detecting changes in expression of ISM2, ADAM12, PST1, PSG7, PST11, PSG9, PSG2 and other genes identified therein, including combinations thereof. A selected gene, gene transcript or protein/peptide expression product, or profiles or signatures formed by combinations of same, detected in a biological fluid of a subject, enables comparison of the corresponding genes, proteins or profiles from that of a reference or control having a normal intrauterine pregnancy. Detection of characteristic changes in the gene profile or protein expression signature of the subject is correlated with a diagnosis of ectopic pregnancy. Various compositions for use in such diagnosis include PCR primer-probe sets or ligands, labeled or immobilized, which are capable of detecting the changes in expression or translation of these targets.

Abstract: In an effort to discover therapies for treating HSP70 related diseases, a previously unidentified hydrophobic pocket was found in the C-terminal domain of DnaK and of human HSP70. A novel chemical scaffold was also discovered for identifying compounds that treat diseases related to this hydrophobic pocket. The compounds have the structure of the formula (I), wherein L, M, and R1-R5 are defined herein and are, therefore, in these therapies, optionally with other pharmaceutical agents such as genotoxic agents. Accordingly these compounds are useful in inhibiting HSP70 or DnaK, reducing HSP70 in mitochondria of a cancer cell, treating malignant neoplastic disease, or inhibiting or reducing bacterial growth. These compounds also resulted in novel methods of screening for a HSP70 inhibitor or DnaK inhibitor by using the three-dimensional structure of the hydrophobic pocket in DnaK or HSP70.

Abstract: The present invention provides a small molecule treatment of diseases/conditions caused by a virus carrying a viral oncoprotein. In one embodiment, the virus which carries the viral oncoprotein is HPV. The small molecule useful herein includes thiadiazolin-3,5-dione compounds having an optionally substituted aryl group bound to one nitrogen atom of said thiadiazolin-3,5-dione compound. The small molecules may also be administered with a compound which inhibits binding of HPV E6 to p53. In one embodiment, the thiadiazolin-3,5-dione compound has formula (I), or a pharmaceutically acceptable salt, prodrug, solvate, or metabolite thereof, wherein R1 and R2 are defined herein.

Abstract: A immunogenic composition is provided for use in methods for treating or preventing the development of a cancer, comprising a nucleic acid sequence encoding a cancer antigen and a nucleic acid sequence encoding fibroblast activation protein (FAP). In one embodiment, the composition comprises a vector comprising a first expression cassette comprising a nucleic acid sequence encoding an antigen of a, operatively linked to an expression control sequence that directs the expression of the antigen in a mammalian host cell. The composition further contains a vector comprising a second expression cassette comprising a nucleic acid sequence encoding fibroblast activation protein (FAP) operatively linked to an expression control sequence directing the expression of FAP in a mammalian host cell. In one embodiment, the cancer is one in which tumor progression depends on the fibroblasts expressing fibroblast activation protein (FAP).

Abstract: The present invention embraces compounds that modulate the activity of Epstein-Barr Nuclear Antigen 1 (EBNA1) protein and use thereof in methods for treating latent Epstein-Barr virus infection.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention relates to targeting the stromal cell population in a tumor microenvironment. For example, in one embodiment, the invention provides a composition that is targeted to fibroblast activation protein (FAP). The invention includes a chimeric antigen receptor (CAR) which comprises an anti-FAP domain, a transmembrane domain, and a CD3zeta signaling domain.

Abstract: The present invention embraces compounds that modulate the activity of Epstein-Barr Nuclear Antigen 1 (BBNA1) protein and use thereof in methods for treating latent Epstein-Barr virus infection. R7 is a substituted or unsubstituted phenyl, pyridyl, or pyrimidinyl group. A pharmaceutical composition comprising a compound of the invention in admixture with a pharmaceutically acceptable carrier is also provide as are methods for modulating the activity of Epstein-Barr Nuclear Antigen 1 (EBNA1) protein and treating a latent EpsteinBarr virus infection with a composition of the present invention.

Abstract: The present invention embraces methods for identifying compounds that modulate the activity of telomerase. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the TRBD, “thumb,” “finger,” and/or “palm” domain; or FP-pocket, PT-pocket or Th-pocket of telomerase and testing the compound for its ability to modulate the activity of telomerase. Compounds selected for interacting with the T-pocket or Fingers-Palm pocket of telomerase are also provided.

Abstract: The present invention embraces methods for identifying compounds that modulate the activity of telomerase. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the TRBD, “thumb,” “finger,” and/or “palm” domain; or FP-pocket, PT-pocket or Th-pocket of telomerase and testing the compound for its ability to modulate the activity of telomerase. Compounds selected for interacting with the T-pocket or Fingers-Palm pocket of telomerase are also provided.

Abstract: The present invention relates to a method for identifying compounds that modulate the activity of p300/CBP. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified lysine-CoA inhibitor binding site, L1 loop, electronegative pocket, or electronegative groove of the HAT domain of p300/CBP and testing the compound for its ability to modulate the activity of p300/CBP. Compositions and methods for preventing or treating diseases or disorders associated with p300/CBP are also provided as is a method for producing a semi-synthetic HAT domain.

Abstract: Methods and compositions are provided for diagnosing or detecting a condition, e.g., lung disease in a mammalian subject by use of a micro-RNA expression level or an expression level profile of multiple miRNA in the peripheral blood mononuclear cells (PBMC) of the subject which is characteristic of COPD or NSCLC. Detection of changes in expression in specific miRNA biomarkers from that of a reference sample or miRNA expression profile are correlated with non-small cell lung cancer (NSCLC) and/or COPD and permit differentiation among healthy subjects, subjects with COPD and subjects with adenocarcinoma or squamous cell carcinoma.

Abstract: Isolated human multipotent adult stem cell and isolated populations of cells that include human multipotent adult stem cells are disclosed. Human hair-follicle derived multipotent adult stem cells and methods of preparing isolated populations of cells that include human multipotent adult stem cells are disclosed. Isolated human hair-follicle derived multipotent adult stem cell that can differentiate in culture into a neuronal cell, a glial cell, a melanocyte cell, a muscle cell, an osteocyte, a chondrocyte, and a lymphocyte. Isolated human hair-follicle derived multipotent adult stem cell that can grow in cell culture in spheres are disclosed.

Abstract: Chimeric protein constructs including a herpesvirus glycoprotein D (gD) and a heterologous polypeptide that interact with herpes virus entry mediator (HVEM) and enhance and enhance an immune response against the heterologous polypeptide and methods for their use are provided.

Abstract: This disclosure provides universal influenza vaccines which can provide extended protection for several years, provide improved protection to circulating influenza strains that were not predicted accurately for annual vaccine manufacturing, and provide protection against newly emerging strains of influenza virus which carry the potential for establishing global pandemics.

Abstract: A immunogenic composition is provided for use in methods for treating or preventing the development of a cancer, comprising a nucleic acid sequence encoding a cancer antigen and a nucleic acid sequence encoding fibroblast activation protein (FAP). In one embodiment, the composition comprises a vector comprising a first expression cassette comprising a nucleic acid sequence encoding an antigen of a, operatively linked to an expression control sequence that directs the expression of the antigen in a mammalian host cell. The composition further contains a vector comprising a second expression cassette comprising a nucleic acid sequence encoding fibroblast activation protein (FAP) operatively linked to an expression control sequence directing the expression of FAP in a mammalian host cell. In one embodiment, the cancer is one in which tumor progression depends on the fibroblasts expressing fibroblast activation protein (FAP).

Abstract: A method for inhibiting tumor cell migration or metastasis of a cancer in a mammalian subject comprises one or more of the steps of administering to a subject a therapeutically effective amount of a composition comprising a molecule that: suppresses focal adhesion kinase (FAK) activity or phosphorylation; suppresses ULK1 kinase activity; suppresses activation or signaling of the mTORC1 (Ser757) pathway; activates AMPK; activates FIP200; or activates LKB1, in a cancer cell. Still another method of inhibiting tumor cell migration involves inhibiting phosphorylation of ULK1 on Ser757 in subjects with lung cancer. Suppressing activation or signaling of the mTORC1 (Ser757) pathway in subjects is in one aspect useful in treating lung cancer.

Abstract: Methods and compositions are provided for diagnosing ovarian cancer in a mammalian subject, preferably in a serum or plasma sample of a human subject. The methods and compositions enable the detection or measurement in the sample or from a protein level profile generated from the sample, the protein level of one or more specified biomarkers. Comparing the protein level(s) of the biomarker(s) in the subject's sample or from protein abundance profile of multiple biomarkers, with the level of the same biomarker(s) or profile in a reference standard, permits the determination of a diagnosis of ovarian cancer, or the identification of a risk of developing ovarian cancer, or enables the monitoring of the status of progression or remission of ovarian cancer in the subject followed during a therapeutic protocol.

Abstract: A high-throughput method for identifying a compound or biomolecule that modulates cell senescence involves simultaneously measuring in a cell population exposed to the test compound or biomolecule, the expression of a senescence marker and cell number, wherein each well contains a single test compound; and determining from said simultaneous measurements whether the test compound increases or decreases cell senescence. In various embodiments, the method is useful is identifying compounds that delay the aging process of normal healthy cells, or identifying a compound useful as a tumor suppressor or identifying a compound useful in the treatment of cancer.

Abstract: Methods and compositions are provided for diagnosing colorectal cancer in a mammalian subject, preferably in a serum or plasma sample of a human subject. The methods and compositions enable the detection or measurement in the sample or from a protein level profile generated from the sample, the protein level of one or more specified biomarkers. Comparing the protein level(s) of the biomarker(s) in the subject's sample or from protein abundance profile of multiple biomarkers, with the level of the same biomarker(s) or profile in a reference standard, permits the determination of a diagnosis of colorectal cancer, or the identification of a risk of developing colorectal cancer, or enables the monitoring of the status of progression or remission of colorectal cancer in the subject followed during a therapeutic protocol.

Abstract: The present invention is a method for identifying agents which modulate microRNA activity. The invention involves contacting a cell harboring a microRNA and a microRNA binding sequence, which is operably linked to a nucleic acid molecule encoding a reporter protein, with a test agent and determining whether the test agent increases or decreases the expression of the reporter protein thereby identifying a microRNA modulator. Antagonists identified by this screening assay are provided, as are methods for using the same to inhibit microRNA activity and prevent or treat disease.