Methods and compositions for drug discovery, analysis and treatment of a proliferative disorder characterized by abnormal cells in a mammalian subject are provided according to aspects of the present invention which include administering a pharmaceutically effective amount of a combination of: a cytotoxic agent, a SET agonist and a SET ribosome antagonist. Methods and compositions according aspect of the present invention incorporate agents effective to regulate and/or affect selective translation in a cell characterized by abnormal proliferation, such as a cancer cell, thereby promoting death of the cell.

A 4D-perfused tumoroid-on-a-chip platform used in personalized cancer treatment. The platform includes a plate with a plurality of bottomless wells that resides atop a microfluidic channel layer, which in turn resides atop a surface acoustic wave (SAW) based sensor layer that is capable of measuring potential pH values of fluids disposed within the platform. The microfluidic channel layer includes a plurality of bioreactors, with each bioreactor including an inlet well, a culture well, and an outlet well. The inlet well, culture well, and outlet well form a closed system via fluid conduits spanning from the inlet well to the culture well, as well as from the culture well to the outlet well. Due to the fluid flow from the plate to the chip, and from the inlet well to the outlet well on the chip through the culture well, target cell (tumoroid) growth is promoted within the culture well.

Described herein are thienopyrimidine compounds of Formula (I), and pharmaceutically acceptable salts, and pharmaceutical compositions thereof. Also provided are methods and kits involving the thienopyrimidine compounds or compositions for treating or preventing proliferative diseases such as cancers (e.g., brain tumors such as DIPGs) in a subject. The invention further provides an embryonic stem cell-based tumor cell model, which can be used for drug screening and disease target identification.

From a cell population containing cardiomyocytes, the cardiomyocytes are extracted using a marker(s) specific to cardiomyocytes, that is, at least one marker selected from CORIN, NCAM1, CRYAB, HBEGF, DMD, ATPIF1, CAV2, ITGAV, DCBLD2, CLIC4, BMPR2, CTSB, TMEM123, USP14, and MIR761.

The present invention relates to a transduced cancer cell line stably expressing a leukemia tumor antigen, wherein the cancer cell line is cervical cancer cells, breast cancer cells, ovarian cancer cells, pancreatic cancer cells, lung cancer cells, or glioblastoma cells. The transduced adherent cell line of the present invention is useful for many pre-clinical applications such as real time cytotoxicity assay or to test the effects of CAR-T cells that target the tumor antigen. The present invention is exemplified by Hela cell line stably expressing CD19.

Disclosed are improved compositions and methods for decreasing blood glucagon levels. As disclosed herein, L-glutamine is a selective stimulator of α-cell proliferation generated when glucagon signaling is interrupted. Therefore, disclosed is a method for treating a subject with hyperglucagonemia, e.g., a subject with diabetes, that involves administering to the subject a composition comprising an L-glutamine inhibitor in an amount effective to decrease blood glucagon levels.

The present disclosure provides multicellular culture models for the study of neuroinflammation, such as to identify novel targets, biomarkers, and therapeutic agents for the diagnosis, prognosis, and treatment of neurodegenerative diseases. Further provided herein are assays for studying neuroinflammation using the present cell culture models.

Compositions and methods disclosed concern an isogenic population of in vitro human embryonic stem cells comprising a disease form of the Huntingtin gene (HTT) at the endogenous HTT gene locus in the genome of the cell; wherein the disease form of the HTT gene comprises a polyQ repeat of at least 40 glutamines at the N-terminus of the Huntingtin protein (HTT). The cell lines of the disclosure comprise genetically-defined alterations made in the endogenous HTT gene that recapitulate Huntington's Disease in humans. Furthermore, the cell lines have isogenic controls that share a similar genetic background. Differentiating cell lines committed to a neuronal fate and fully differentiated cell lines are also provided and they also display phenotypic abnormalities associated with the length of the polyQ repeat of the HTT gene. These cell lines are used as screening tools in drug discovery and development to identify substances that fully or partially revert these phenotype abnormalities.

Described herein are particular infection model systems, methods of studying infection, and method of screening compounds in various model systems. Particularly, SARS-CoV-2 is studied in these organ and infection models.

Provided herein are compositions and methods describing the generation and use of in vitro pro-organs using microparticle scaffolds.