Abstract: The invention includes compositions and methods of generating a chimpanzee-derived adenovirus AdC6 or AdC7 vector vaccine comprising a deletion of E1, a deletion of E3 ORF3, ORF4, ORF5, ORF6, and ORF7 and a sequence encoding HIV protein gp140, gp160 or Gag, methods of treating and/or preventing or immunizing against HIV and methods of inducing an effector T cell, memory T cell and B cell immune response in a mammal administered the composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a mammal as well as a protein expression system.

Abstract: Methods and compositions are described for enhancing tissue regeneration or wound repair in a mammalian subject comprising a composition comprising (a) a proline hydroxylase inhibitor component or molecule that increases or upregulates HIF1a and (b) a carrier component comprising a hydrogel.

Abstract: In an effort to discover therapies for treating diseases caused by EBV, a novel screening assay for identifying compounds that reactivate EBV latent infection and a family of small molecules based on a tetrahydrocarboline backbone were discovered. Specifically, the compounds have the structure of the formula (I), wherein R1-R11 are defined herein and activate/reactivate EBV in a variety of cell types in a patient and are, therefore, useful in preventing or treating EBV-positive cancer, optionally with an anti-viral agent. In screening these compounds, novel compositions, EBV-positive cell lines, and methods are provided.

Abstract: In some embodiments, therapeutic treatments for a disease such as a cancer are disclosed, including pharmaceutical compositions and methods of using pharmaceutical compositions for treating the cancer wherein the cancer cells overexpress arginine methyltransferase CARM1. In some embodiments, the therapeutic treatments disclosed include methods comprising the step of administering a therapeutically effective dose of an enhancer of zeste homolog 2 (EZH2) inhibitor to a subject, including a human subject, wherein the cancer cells of the subject overexpress arginine methyltransferase CARM1. In some embodiments, the EZH2 inhibitors are administered in conjunction with platinum-based antineoplastic drugs.

Abstract: A nucleic acid sequence is provided that encodes a chimeric protein comprising a ligand that comprises a naturally occurring or modified follicle stimulating hormone sequence, e.g., an FSHp sequence, or fragment thereof, which ligand binds to human follicle stimulating hormone (FSH) receptor, linked to either (a) a nucleic acid sequence that encodes an extracellular hinge domain, a transmembrane domain, a co-stimulatory signaling region, and a signaling endodomain; or (b) a nucleic acid sequence that encodes a ligand that binds to NKG2D. The vector containing the nucleic acid sequence, the chimeric proteins so encoded, and modified T cells expressing the chimeric protein, as well as method of using these compositions for the treatment of FSHR-expressing cancers or tumor cells are also provided.

Abstract: A method of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided.

Abstract: Compositions and methods described herein include somatic cells that are competent for reprogramming and malignant transformation and are characterized by a reduction of the levels of Sp100 in the cells, cells having markers of pluripotent stem cells, and methods for preparing same. Methods for reversably regulating aging or reprogramming to pluripotency in a somatic cell involve modulating the expression of Sp100 therein. Methods and compositions for retarding the growth of or suppressing unwanted cell proliferation involve expressing, inducing expression of, or upregulating, Sp100 in a targeted cell that is undergoing unrestricted proliferation or replication or increasing exposure to Sp100 in the environment or microenvironment of the targeted cell. Also disclosed are methods for treating a proliferative disease or condition by increasing expression or levels of Sp100 in the targeted cell or its environment.

Abstract: An isoform-level gene panel is disclosed that can accurately classify a glioblastoma subtype from a tumor sample. Such an isoform level gene panel comprises the 121 to 214 target isoforms identified in Table 1. Also disclosed are reagents for quantitatively detecting the expression or activity of the target isoforms of Table 1 in a patient sample. For example, such ligands can be PCR primer and probes sets. This isoform-level gene panel and reagents for detection of the isoforms are useful in an isoform-level assay for diagnosis of the molecular subtype of a glioblastoma in a patient. The assay employs algorithms and a novel computer program that performs the functions of FIG. 8. In one aspect, the assay is a high-throughput format.

Abstract: A method of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided.

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: Methods and compositions are provided for diagnosing ectopic pregnancy in a mammalian subject by detecting changes in expression of the selected genes, gene fragments or transcripts or expression products, or changes in the expression levels of one or more of proteins or peptide fragments, identified in Table 2 and FIGS. 8 and 9 herein. A selected gene, gene transcript or protein/peptide expression product, or profiles or signatures formed by combinations of same, detected in a biological fluid, preferably sera, 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.

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: A diagnostic reagent or device comprises at least one ligand capable of specifically complexing with, binding to, or quantitatively detecting or identifying the biomarker chloride intracellular channel protein 4 (CLIC4) or an isoform, pro-form, modified molecular form including posttranslational modification, or unique peptide fragment or nucleic acid fragment thereof. An alternative diagnostic reagent or device comprises ligand or ligands capable of specifically complexing with, binding to, or quantitatively detecting or identifying multiple tropomyosin biomarkers. Optionally, such reagent or device includes a signaling molecule and/or a substrate on which the ligand is immobilized. Other reagents and methods of diagnosing ovarian cancer include use of CLIC4 ligands and/or multiple tropomyosin ligands with an additional ovarian cancer biomarker. For example, CLIC4 combined with one or more of CLIC1 and/or one or multiple members of the tropomyosin family, e.g.

Abstract: Compositions, e.g., therapeutic agents, and methods are provided for modulating gene and protein expression of Forkhead Box protein 1 (Foxp1). The therapeutic agents include short nucleic acid molecules that modulate gene and protein expression of Forkhead Box protein 1 (Foxp1) expression, viral vectors containing such molecules, T cells transduced with these viruses for adoptive therapies, and any small molecules that bind to and inactivate Foxp1. These compounds and methods have applications in cancer therapy either alone or in combination with other therapies that stimulate the endogenous immune system in the environment of the cancer, e.g., tumor.

Abstract: The invention provides EBNA1 inhibitors, and pharmaceutical compositions comprising the same, that are useful for the treatment of diseases caused by EBNA1 activity such as, but not limited to, cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and/or rheumatoid arthritis. The compounds and compositions of the invention are further useful for the treatment of diseases caused by latent Epstein-Barr Virus (EBV) infection. The compounds and compositions of the invention are further useful for the treatment of diseases caused by lytic EBV infection.

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 of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided.

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: Methods and compositions are described for enhancing tissue regeneration or wound repair in a mammalian subject comprising a composition comprising (a) a proline hydroxylase inhibitor component or molecule that increases or upregulates HIF1a and (b) a carrier component comprising a hydrogel.

Abstract: This disclosure provides replication-incompetent adenoviral vectors useful in vaccine development and gene therapy. The disclosed vectors comprise a selective deletion of E3 and are particularly useful for preparation of vaccines development and for gene therapy using toxic transgene products that result in vector instability that occurs when the entire E3 domain is deleted.