Disclosed herein is a method for treating a solid tumor in a subject that involves assaying a sample from the subject for expression of two or more Histone deacetylases (HDACs); determining a response score from the expression of the two or more HDACs, wherein the response score predicts whether the subject will respond to combination immunotherapy and HDAC inhibitor therapy; and administering to the subject a therapeutically effective amount of a combination of immunotherapy and an HDAC inhibitor.

The present disclosure provides a model of human fibrolamellar hepatocellular carcinoma (FL-HCC) cells maintained as a transplantable tumor line in a host and a method to establish a transplantable human FL-HCC tumor line. Methods of ex vivo cultures of the FL-HCC are provided. Methods of diagnosing and treating FL-HCC tumors are also provided.

The present invention provides agents and compositions for modulating expression (e.g., enhanced or reduced expression) of a secreted frizzled related protein 1 (SFRP1) gene by targeting an SFRP1 expression control region and methods of use thereof for treating an SFRP1 associated disorder, e.g., hair loss.

The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription.

The present disclosure provides, in some embodiments, methods for treating a neurodegenerative disease in a subject using a histone deacetylase 2 (HDAC2)/Sp3 inhibitor, which may be a peptide inhibitor comprising the carboxyl-terminus of HDAC2, and related compositions.

The invention is based on a finding that silencing HDAC4gene sensitizes cancer cells for apoptosis-inducing activity of certain small molecule chemotherapeutic agents. Thus, the invention is directed to a respective combination therapy, sensitization method and pharmaceutical compositions.

The present invention relates to Abhydrolase containing domain 5 (ABHDS) and N-terminal fragments of HDAC4 (HDAC4-NT) and variants of the aforementioned peptides for the treatment and prevention of heart failure. The present invention further provides vectors for the cardiomyocyte-specific expression of said peptides and a test system comprising ABHDS for the identification of novel compounds which are useful for the treatment of heart failure.

The instant invention provides workflows for the design and characterization of mechanism-based sirtuin modulating compounds, including new or improved sirtuin activating compounds. Workflows for the design of mechanism-based sirtuin activating compounds are provided, based on conditions that must be satisfied by activators if they are to exploit the common catalytic mechanism of all sirtuin enzymes and hence increase catalytic efficiency for any sirtuin and any substrate.

Provided is a compound that comprises the structure:

##STR00001## where SIG is a signaling molecule and R.sup.3 is a formyl, a succinyl, a methyl succinyl, or a myristoyl. Also provided is a kit is provided that comprises the above compound, with instructions for determining the presence of the enzyme. Additionally, a method is provided for determining whether a sample has an enzyme that removes a succinyl, a methyl succinyl, a formyl, or a myristoyl moiety from an -amino of a lysine. Also provided is a method of determining whether a molecule inhibits an enzyme that removes a succinyl, a methyl succinyl, a formyl, or a myristoyl moiety from an -amino of a lysine.

Engineered CRISPR-Cas9 nucleases with improved specificity and their use in genomic engineering, epigenomic engineering, genome targeting, and genome editing.