Abstract: Described herein are methods for genetically modifying expanded hematopoietic cells comprising obtaining a quantity of hematopoietic cells, culturing the quantity of hematopoietic cells in the presence of at least one histone deacetylase inhibitor (HDACi) and at least one growth factor to expand the hematopoietic cells, and contacting the expanded hematopoietic cells with a nucleic acid sequence, wherein the nucleic acid sequence modifies the quantity of expanded hematopoietic cells. Further described herein are compositions comprising the genetically modified hematopoietic cells produced by these methods.

Abstract: Disclosed herein are methods for solubilizing and isolating nuclear proteins from cells.

Abstract: Provided herein are compounds useful as inhibitors of CBX. Also described are pharmaceutical compositions and medical uses of these compounds.

Abstract: Described herein are methods and compositions which lead to the efficient ex vivo expansion of hematopoietic cells, such as hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells HSPCs. Using combinations of small molecule drugs and cytokines/growth factors/grown factors targeting epigenetic status in cells, significant improvements in the expansion of cells was observed, including cells isolated from human cord blood or peripheral mobilized stem/progenitor cells. Multiple genes implicated in HSPC function were unperturbed, and efficiency of genomic editing using lentivirus was greatly enhanced following treatment. These novel approaches could be used therapeutically in a variety of hematopoietic transplantation settings, in addition to benefiting gene therapy techniques.

Abstract: The present invention relates to compound that bind Histone H3-lysine79 (H3K79) methyl transferase (DOTIL). The disclosed compounds are useful as for assessing the activity of DOTIL and for identifying inhibitors of DOTIL. Described herein are probes useful for both assessing the activity of DOTIL and identifying inhibitors of DOTIL. These probes can be used in various assays, including Amplified Luminescent Proximity Homogeneous Assays (“ALPHA” assays), Differential Scanning Fluorimetry (DFS) Assay, and Fluorescence Polarization (FP) assays used for high-throughput screening (HTS) for small molecule drug discovery. The compounds can also be used as a pull down agent for target identification.

Abstract: Provided herein are inhibitors of DOT1L of formula (I) useful for treating diseases or disorders associated with DOT1L: in which R1 is defined in the specification. An exemplary DOT1L inhibitor provided herein exhibits a biological half-life of 12.6 h. Methods for treating diseases associated with DOT1L are also provided.

Abstract: The present invention relates to compound that bind Histone H3-lysine79 (H3K79) methyl transferase (DOTIL). The disclosed compounds are useful as for assessing the activity of DOTIL and for identifying inhibitors of DOTIL. Described herein are probes useful for both assessing the activity of DOTIL and identifying inhibitors of DOTIL. These probes can be used in various assays, including Amplified Luminescent Proximity Homogeneous Assays (“ALPHA” assays), Differential Scanning Fluorimetry (DFS) Assay, and Fluorescence Polarization (FP) assays used for high-throughput screening (HTS) for small molecule drug discovery. The compounds can also be used as a pull down agent for target identification.

Abstract: Provided herein are inhibitors of DOT1L useful for treating diseases or disorders associated with DOT1L. An exemplary DOT1L inhibitor provided herein exhibits a biological half-life of 12.6 h. Methods for treating diseases associated with DOT1L are also provided.