Abstract: Methods and compositions are provided for the treatment of Alzheimer's Disease (AD) by administering to a patient a therapeutically effective amount of an agent that inhibits signaling mediated by a bone morphogenetic protein type 1A receptor (BMPR-1A) or bone morphogenetic protein type 2 receptor (BMPR-2). Also provided are methods and compositions to increase the rate of neural stem cell self-renewal.

Abstract: Provided herein is A compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein the various substituents are described herein.

Abstract: The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Abstract: The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Abstract: Methods and compositions are provided for the treatment of Alzheimer's Disease (AD) by administering to a patient a therapeutically effective amount of an agent that inhibits signaling mediated by a bone morphogenetic protein type 1A receptor (BMPR-1A) or bone morphogenetic protein type 2 receptor (BMPR-2). Also provided are methods and compositions to increase the rate of neural stem cell self-renewal.

Abstract: The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Abstract: This disclosure provides data showing that LEFTY inhibits differentiation-promoting pathways such as BMP7/pSMAD5 in breast cancer cell lines, over and above its known role of inhibiting Nodal/pSMAD2. LEFTY competes with BMP7 to bind to its cell surface receptor BMPR2, leading to inhibition of pSMAD5. The LEFTY-BMPR2 interaction is dominant over BMP-BMPR2 in tumorigenic cells, resulting in diminished pSMAD status, whereas in non-tumorigenic cells, there is minimal LEFTY-BMPR2 interaction, increased BMP7-BMPR2 association, and elevated pSMAD. Compositions and methods for inducing or inhibiting expression and/or the activity of LEFTY and BMP proteins are described, which can be used in diagnosis and therapy of cancer and other conditions, and to promote proliferation of stem cells.

Abstract: Processes to infer stemness, cell lineage, and/or differentiation status are provided. In some instances, single cell RNA sequencing is used to infer a cell's stemness, cell lineage, and/or differentiation status. In some instances, a collection of cells is ordered based on each cell's differentiation status.

Abstract: Reagents and methods for epigenetic profiling using targeted chromatin ligation are disclosed. The method utilizes oligonucleotide adapters complexed with antibodies specific for DNA-binding proteins of interest and proximity ligation to tag fragmented chromatin with the adapters. Chromatin fragments having ligated adapters are amplified and sequenced with primers that hybridize to the adapters. This method can be used in epigenetic profiling, for example, for mapping histone modification patterns as well as transcriptional regulatory sites.

Abstract: A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Abstract: The present invention provides a biomarker, namely CDX2, and surrogate CDX2 biomarkers, the expression level of which is useful in predicting response of cancer patients to therapy with an EGFR inhibitor.

Abstract: Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.

Abstract: Methods and compositions are provided for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal. Aspects of the methods include inhibiting H2A deubiquitinating enzyme activity in cells, e.g. by administering an effective amount of an H2A deubiquitinating enzyme antagonist. Also provided are screens to identify therapeutics for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal.

Abstract: A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Abstract: The present invention relates to compositions and methods for characterizing, regulating, diagnosing, and treating cancer. For example, the present invention provides compositions and methods for inhibiting tumorigenesis of certain classes of cancer cells, including breast cancer cells and preventing metastasis. The present invention also provides systems and methods for identifying compounds that regulate tumorigenesis.

Abstract: A small percentage of cells within an established tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Abstract: Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.

Abstract: Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.

Abstract: Methods and compositions are provided for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal. Aspects of the methods include inhibiting H2A deubiquitinating enzyme activity in cells, e.g. by administering an effective amount of an H2A deubiquitinating enzyme antagonist. Also provided are screens to identify therapeutics for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal.

Abstract: The invention provides methods for treating cancer via administering to a patient having a solid tumor a therapeutically effective amount of an antibody against Delta-like ligand 4(Dll4) or other Notch pathway components. The solid tumor may comprise solid tumor stem cells.