ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. It has been found that in cells expressing functional ABCG2, ABCB1, or ABCC1 transporters, cellular PG fluorescence is strongly reduced. The invention relates to methods and uses of fluorescein derivative ester compounds of formula Ia which are analogs of PG for assessing ABC transporter activity of ABC multidrug transporters. The present accumulation assay is a novel tool for the parallel determination of the function of the multidrug transporters, in particular ABCG2, ABCB1, and ABCC1. The assay is applicable for diagnostic purposes and also allows the selection, separation and culturing of selected cell populations expressing such transporters.

A method of detecting integrated stress response activity in living cells comprising inducing UL148-marker expression, scanning the cells to determine if the UL148 is punctate or diffuse, and ranking the level of ISR activity based on how punctate the UL148 is in the cell. The marker may be a fluorescent marker. The fluorescent marker may be Green fluorescent protein. The cell may be an epithelial cell. The cells may be ARPE-19 epithelial cells carrying a doxycycline inducible gene expression cassette encoding UL148-GFP and treating the cells for 18 hours with 100 ng/mL doxycycline hyclate to induce UL148-GFP expression. The cells may have an inducible gene expression cassette encoding UL148-marker expression. The UL148-marker expression may be induced by the cell being treated with an antibiotic. The method may include adding marker to the cells. The cells may be mutated to express UL148-marker upon inducement. A kit to conduct the method.

A method of modulating protein exocytosis is provided. The method comprising contacting a cell with an agent that modulates the ubiquitin pathway in the Golgi, thereby modulating protein secretion.

In various aspects the invention provides methods of predicting sensitivity of a cancer cell to a therapeutic agent by contacting a test cell population BH3 domain peptide; measuring the amount of BH3 domain peptide induced mitochondrial outer membrane permeabilization in the test cell population; and comparing the amount of BH3 domain peptide induced mitochondrial outer membrane permeabilization in the test cell population to a control cell population that has not been contacted with the therapeutic agent. An increase in mitochondrial membrane permeabilization in the test cell population compared to the control cell population indicates the cell is sensitive to the therapeutic agent.

The present invention provides for compositions and methods for treating, ameliorating or preventing a lysosomal storage disease by administering to a patient suffering front a lysosomal storage disease a P97 conjugated with an enzyme which is capable of transportation into the lysosomes of cells on either sides of the blood brain barrier.

Provided herein are conjugate molecules containing a substrate for a nucleoside transport pathway linked to an active agent, wherein the conjugate can be transported into a cell or into the nucleus of a cell via a cellular nucleoside transport pathway. Further provided are methods of delivering a conjugate molecule to a target cell expressing a nucleoside transport pathway, wherein the conjugate contains a substrate for the nucleoside transport pathway linked to an active agent. Also provided are methods for screening for conjugates that are transported by nucleoside transport pathways. Further provided are methods of treating a patient having a disease or disorder affecting tissues expressing nucleoside transport pathways, in which a conjugate containing an agent effective in treating the disorder is administered to the patient. Also provided are methods of treating a patient having an autoimmune disorder involving administering to the patient a compound that inhibits a nucleoside transport pathway.

A novel vial for holding a segment of epithelial tissue is provided. The vial is easy to assemble and allows horizontal alignment of the tissue sample. A device comprising the vial, to methods for generating the device, and to a multitude of said devices which allow medium throughput measurements of absorption, transport and/or secretion across an epithelial tissue are also provided.

The present invention provides for compositions and methods for treating, ameliorating or preventing a lysosomal storage disease by administering to a patient suffering from a lysosomal storage disease a P97 conjugated with an enzyme which is capable of transportation into the lysosomes of cells on either side of the blood brain barrier.

The present invention relates to modulators of ATP-Binding Cassette (ABC) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Bioluminescence resonance energy transfer (BRET) biosensors for assessing the intracellular localization, internalization and trafficking into cellular compartments of proteins such as receptors, and other biomolecules such as second messengers, are disclosed. These biosensors, which are dependent on the concentration/density of the BRET donor and acceptor in cellular compartments rather that specific protein-protein interactions, use a Renilla GFP/Luc BRET pair, which allows the robust and reproducible monitoring of protein trafficking/localization, with a sensitivity compatible with high-throughput screening (HTS). The use of these biosensors for various applications, including assessing/monitoring protein endocytosis, recycling and intracellular trafficking, receptor maturation/rescue by pharmacological chaperones, various endocytosis/exocytosis processes, activation/inhibition, as well as biomolecule concentration/density in different cellular compartments, is also disclosed.