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Mapping the Genetic Architecture of Gene Expression in Human Liver
TLDR
This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases.
CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability.
TLDR
Using tumor cell lines and primary patient samples representing multiple B-cell malignancies, it is demonstrated that constitutive phosphatidylinositol-3-kinase pathway activation is p110δ-dependent, providing a rationale for the ongoing clinical evaluation of CAL-101.
Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia.
TLDR
The clinical utility of inhibiting the PI3Kδ pathway with idelalisib is demonstrated and the findings support the further development of idELalisib in patients with CLL.
Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines.
TLDR
Researchers studied the gene expression profiles of T24 bladder and MDA breast carcinoma cells treated with three HDAC inhibitors to understand the genomic effects of HDAC inhibition on gene transcription, which may be responsible for antitumor effects.
Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: A resource for investigations into drug disposition
TLDR
A comprehensive data set of xenobiotic transporter gene expression profiles in humans and the pre-clinical species mouse, rat, beagle dog and cynomolgus monkey is generated.
Drug-induced phospholipidosis: issues and future directions
TLDR
There is an abundance of data providing an understanding of potential mechanisms for the induction of phospholipidosis; however, the process is likely to be complex and may differ from one drug to another and the functional consequences of the presence of this condition on cellular or tissue function are not well understood.
Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver.
TLDR
Most P450s were positively correlated among themselves and were highly correlated with known regulators as well as thousands of other genes enriched for pathways relevant to the metabolism of drugs, fatty acids, amino acids, and steroids.
Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma.
TLDR
iNHL evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma, idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL.
Activators of the rat pregnane X receptor differentially modulate hepatic and intestinal gene expression.
TLDR
Results suggest that ligand-mediated activation of PXR and induction of hepatic, rather than small intestinal, drug metabolism genes would contribute to the increased metabolism of orally administered pharmaceuticals.
Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile
TLDR
Determination of the inhibitory potential of anti-immunoglobulin M–induced CD69 expression in human peripheral blood mononuclear cells and whole blood demonstrated that acalabrutinib is a potent functional BTK inhibitor.
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