Proof of drug-target engagement in physiologically-relevant contexts is a key pillar of successful therapeutic target validation. We developed two orthogonal technologies, the cellular thermal shift assay (CETSA) and a covalent chemical probe reporter approach (harnessing sulfonyl fluoride tyrosine labeling and subsequent click chemistry) to measure the occupancy of the mRNA-decapping scavenger...

DNA damage and repair is a fundamental process that plays an important role in cancer treatment. Base excision repair (BER) is a major repair pathway that often leads to drug resistance in DNA-targeted cancer chemotherapy. In order to measure BER, we have developed a near infrared (NIR) fluorescent probe. This probe binds to a key intermediate, termed apurinic/apyrimidinic (AP) site, in the BER...

In this paper, a new live-cell permeable, fluorescent light-up probe comprised of a hydrophilic caspase-specific Asp-Glu-Val-Asp (DEVD) peptide and a hydrophobic tetraphenylethene pyridinium unit has been developed for in vivo cell apoptosis imaging and drug screening. The probe shows a specific light-up response to activated caspase-3/7 with a high signal-to-background ratio. The significant f...

Acetylation is a well-characterized histone modification, which plays important roles in controlling epigenetic gene expression, and its malfunction is tightly associated with cancer. By taking advantage of the specific binding of BRD4 to acetylated lysine residues, we developed a FRET-based probe for visualizing histone H3 acetylation in living cells. BRD4, a protein known to be involved in ac...

Growing concerns about the spread of multidrug-resistant tuberculosis (MDR-TB) and the emergence of extensively drug-resistant TB have triggered substantial interest in the development and application of rapid tests for the detection of drug-resistant TB. Molecular assays to detect gene mutations that signal drug resistance are widely recognized as being most suited for rapid diagnosis. Among m...

Hepatocellular and cholestatic forms of drug-induced liver injury (DILI) are major reasons for late-stage termination of small-molecule drug discovery research projects. Biochemical serum markers are limited in their ability to sensitively and specifically detect both of these common DILI forms in preclinical models, and tissue-specific approaches to assessing this are labor intensive, requirin...

A number of chronic brain diseases are increasingly being treated by the implantation of electrically active probes into specific brain regions. Our goal is to develop more tissue compatible miniaturized probes improving probe function and controlling any adverse effects of probe implantation [1]. Optimization of tissue compatibility requires locally delivered drug therapy that can be altered a...

susceptibility-weighted imaging (swi) has continued to develop into a powerful clinical tool to visualize venous structures and iron in the brain and to study diverse pathologic conditions. it is a new art which evaluates and exploits the properties of blood, iron and other tissues. it is a magnitude or filtered phase images or combination of both, obtained with high-resolution 3d fully velocit...