Abstract: Presented are methods of assessing the teratogenicity of agents by measuring the degradation of SALL4, and related compounds with reduced teratogenicity. Provided herein is a method for assessing the teratogenicity of an agent comprising: contacting an agent with SALL4; and measuring levels of SALL4, wherein the agent is teratogenic if SALL4 levels are substantially reduced in the presence of the agent relative to in the absence of the agent.

Abstract: The present invention provides methods for screening and diagnosing prostate cancer based on a correlation between cancer cell growth, cancer lethality or recurrence and the expression level of ZFP36 or NEDD9 and PTEN in conjunction with ZFP36. The disclosure also provides methods for screening and diagnosing prostate cancer based on a correlation between cancer lethality and the genotype of rs1910301 SNP. Also provided are methods for treating prostate cancer comprising providing a treatment or monitoring based on the expression level of ZFP36, the expression level of NEDD9, and the expression level of ZFP36 in conjunction with PTEN levels or the genotype of rs1910301 SNP.

Abstract: Described herein are compositions and methods of using single-cell RNA-sequencing to identify treatment resistance in patients with ovarian cancer. Also, described herein are compositions and methods for treatment targeting resistance in patients with ovarian cancer.

Abstract: Provided herein are STING and SPARCS genes as biomarkers for determining an effective therapy for treating cancer. Further provided are methods for treating cancer using said biomarkers.

Abstract: The present invention provides compositions and methods for the treatment or prevention of a neurological disease or disorder of the central nervous system (e.g., a storage disorder, lysosomal storage disorder, neurodegenerative disease, etc.) by reconstitution of brain myeloid cell and microglia upon transplantation of hematopoietic cells enriched in microglia reconstitution potential. The invention also provides compositions and methods for ablating and reconstituting microglia.

Abstract: The present invention provides compositions and methods for treating cancers with reduced or absent CDH1 using a RHOA dominant negative polypeptide or biologically active fragment thereof, and/or a nucleic acid encoding a RHOA dominant negative polypeptide or biologically active fragment thereof.

Abstract: Provided herein are nanoparticles which enhance the immunogenicity of antigens for use in Beta coronavirus (e.g., MERS-CoV, SARS-CoV-1, or SARS-CoV-2) vaccines, as well as immunogenic compositions comprising the antigen nanoparticles and additional adjuvants for further enhancing immunogenicity.

Abstract: The disclosure relates to cell-permeable stabilized peptide modules and methods of use for e.g., cellular delivery of cargoes.

Abstract: Structurally stabilized, e.g., stapled, peptides with the ability to translocate through microbial cell membranes to the interior of microbial cells and exert a biological activity there are provided, as are methods of designing, making and using such peptides.

Abstract: Methods for predicting risk of developing colorectal cancer, for treating colorectal cancer, and reducing risk of developing colorectal cancer.

Abstract: The application relates to a compound having Formula X: which modulates the activity of HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, plays a role.

Abstract: The present invention relates to methods, compositions and kits for treatment of ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to the use of novel classes of compounds, i.e. inhibitors of RSK (p90S6K); inhibitors of p70S6K; and inhibitors of rps6, to treat ribosomal disorders and ribosomopathies. In some embodiments, the invention relates to the use of specific Chk2 inhibitors and to the use of specific phenothiazine derivatives to treat ribosomal disorders and ribosomopathies, e.g. DBA.

Abstract: The present disclosure provides compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK) (e.g., Janus kinase 2 (JAK2)) and/or cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 11 (CDK11)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: Provided herein are bifunctional compounds that bind tau protein and/or promote targeted ubiquitination for the degradation of tau protein. In particular, provided are compounds that can bind tau protein, a protein whose aggregation is implicated in a variety of neurodegenerative disease (e.g., tauopathies), and can promote its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon), which can ubiquitinate tau protein, marking it for proteasomal degradation. Also provided are radiolabeled forms of the bifunctional compounds, pharmaceutical compositions comprising the bifunctional compounds, methods of detecting and/or diagnosing neurological disorders, methods of detecting and/or diagnosing pathological aggregation of tau protein (e.g., in the central nervous system), methods of treating and/or preventing neurological disorders, and methods of promoting the degradation of tau protein by E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.

Abstract: The present application relates to compounds comprising an ester, a thioester, or a hydrazide moiety and methods of synthesizing these compounds. The present application also relates to pharmaceutical compositions containing the compounds and methods of treating cell proliferative disorders mediated by the Hedgehog (Hh) signaling pathway, such as cancer, by administering the compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: An isolated nucleic acid molecule encoding a mutant MEK1 protein having MEK1 activity is disclosed. The mutant MEK1 protein comprises an amino acid substitution at position 121 of wild-type MEK1 shown in SEQ ID NO: 2. The amino acid substitution confers resistance to one or more RAF or MEK inhibitors on a cell expressing the mutant MEK1 protein.

Abstract: Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

Abstract: The present invention provides novel compounds of Formulae (I?) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g.

Abstract: DCAF15 is a substrate recognition (adaptor) protein of E3 ubiquitin ligase. Disclosed herein are compounds that recruit ubiquitin ligase CRL4DCAF15, to a target RNA recognition motif (RRM), causing its degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

Abstract: The present invention relates to methods for identifying, assessing, preventing, and treating cancer (e.g., head, neck, and/or lung cancers in humans). A variety of PD-L1 isoform biomarkers are provided, wherein alterations in the copy number of one or more of the biomarkers and/or alterations in the amount, structure, and/or activity of one or more of the biomarkers is associated with cancer status and indicates amenability to treatment or prevention by modulating PD-1 and/or PD-L1 levels.