Abstract: The present invention provides methods for the treatment of cancers by administration of inhibitors of the PI3K-AKT-mTORCl pathway (or components downstream of this pathway such as SREBP and SCD1) and agents that induce ferroptosis to subjects in need thereof. The present invention also provides various related compositions and related methods.

Abstract: The present disclosure provides, among other things, methods and compositions for diagnosing and treating stress-induced injuries, hypoxia in particular. The present invention is based, in part, on the novel discovery that a metabolite, L-2-hydroxyglutarate, and certain enzymes and substrates regulating its metabolism, mediate stress-induced cellular mechanisms. In some embodiments, provided methods and compositions are used to diagnose and treat diseases with hypoxia-induced injuries. In some embodiments, provided methods and compositions are used to modulate cell pluripotency or differentiation in vivo or in vitro.

Abstract: The present disclosure provides highly efficient, non-invasive, and reversible methods for selectively enriching pluripotent cells (e.g., human pluripotent cells and mouse pluripotent cells) in a cell population using a glutamine-deficient medium. The presently disclosed methods have the advantageous of efficiently enriching pluripotent cells in a heterogenous cell population without altering the biological properties of any individual cells.

Abstract: Disclosed herein are compositions, systems, and methods for modulating proliferation, differentiation and pluripotency of cells.

Abstract: The present invention provides biomarkers for sensitive, specific, accurate and quantitative diagnosis and assessment of chronic hypoxia. In particular, the present invention provides 2-hydroxyglutarate as a biomarker that is differentially produced in chronic hypoxia. Furthermore, embodiments of the invention are able to differentiate between chronic and acute hypoxia. Assays for levels of 2-hydroxyglutarate may be used alone or in conjunction with additional biomarkers of hypoxia to increase the precision of analysis. In particular embodiments of the invention, the level of 2-hydroxyglutarate and at least one second biomarker may be assayed to generate a hypoxic profile that can be compared to a reference or control profile, thereby diagnosing a subject as normoxic, chronically hypoxic, or acutely hypoxic.

Abstract: Methods and compositions for treating cancer and other disorders associated with undesired cellular proliferation are provided comprising administering to a subject in need thereof an amino acid mixture, wherein the amino acid mixture comprises glycine, optionally comprising at least a 2:1 molar ratio of glycine to serine.

Abstract: Disclosed herein are compositions, systems, and methods for modulating proliferation, differentiation and pluripotency of cells.

Abstract: Disclosed herein are compositions and methods for detecting and treating cancer. In some embodiments, the cancer is characterized by activation of Ras.

Abstract: Methods and compositions for treating cancer and other disorders associated with undesired cellular proliferation are provided comprising administering to a subject in need thereof an amino acid mixture, wherein the amino acid mixture comprises glycine, optionally comprising at least a 2:1 molar ratio of glycine to serine.

Abstract: The present invention provides methods for the induction and monitoring of T cell exhaustion in vitro. The methods are effective for both human and non-human T cells, and for both antigen-specific and polyclonal T cells. The present invention also provides methods to screen for and/or evaluate pharmacologic agents that can either induce or reverse T cell exhaustion. The present invention also provides certain agents that can reverse T cell exhaustion.

Abstract: The present disclosure provides, among other things, methods and compositions for diagnosing and treating stress-induced injuries, hypoxia in particular. The present invention is based, in part, on the novel discovery that a metabolite, L-2-hydroxyglutarate, and certain enzymes and substrates regulating its metabolism, mediate stress-induced cellular mechanisms. In some embodiments, provided methods and compositions are used to diagnose and treat diseases with hypoxia-induced injuries. In some embodiments, provided methods and compositions are used to modulate cell pluripotency or differentiation in vivo or in vitro.

Abstract: The present disclosure provides, among other things, methods and compositions for diagnosing and treating stress-induced injuries, hypoxia in particular. The present invention is based, in part, on the novel discovery that a metabolite, L-2-hydroxyglutarate, and certain enzymes and substrates regulating its metabolism, mediate stress-induced cellular mechanisms. In some embodiments, provided methods and compositions are used to diagnose and treat diseases with hypoxia-induced injuries. In some embodiments, provided methods and compositions are used to modulate cell pluripotency or differentiation in vivo or in vitro.

Abstract: Methods and compositions for treating cancer and other disorders associated with undesired cellular proliferation are provided comprising administering to a subject in need thereof an amino acid mixture, wherein the amino acid mixture comprises glycine, optionally comprising at least a 2:1 molar ratio of glycine to serine.

Abstract: Disclosed herein are compositions and methods for detecting and treating cancer. In some embodiments, the cancer is characterized by activation of Ras.

Abstract: Methods of treating an individual who has been identified as having glycolysis dependent cancer are disclosed. The methods comprise the step of: administering to suc an individual a combination of an anti-cancer composition that renders the cancer incapable of glycolysis and an autophagy inhibitor. Pharmaceutical compositions and kits comprising that renders the cancer incapable of glycolysis and an autophagy inhibit are also disclosed. Methods of treating an individual who has a disease characterized b cell degeneration and cell death due to autophagy are disclosed. The methods comprise administering to the individual a permeable form of a metabolic substrate that can be oxidized in the tricarboxylic acid cycle to produce NADH. Methods for identifying an autophagy inhibitor comprising performing a test assay using an apopto sis-resistant cell are disclosed.

Abstract: The present disclosure provides, among other things, methods and compositions for diagnosing and treating stress-induced injuries, hypoxia in particular. The present invention is based, in part, on the novel discovery that a metabolite, L-2-hydroxyglutarate, and certain enzymes and substrates regulating its metabolism, mediate stress-induced cellular mechanisms. In some embodiments, provided methods and compositions are used to diagnose and treat diseases with hypoxia-induced injuries. In some embodiments, provided methods and compositions are used to modulate cell pluripotency or differentiation in vivo or in vitro.

Abstract: Disclosed herein are compositions, systems, and methods for modulating proliferation, differentiation and pluripotency of cells.

Abstract: Methods and compositions for treating cancer and other disorders associated with undesired cellular proliferation are provided comprising administering to a subject in need thereof an amino acid mixture, wherein the amino acid mixture comprises glycine, optionally comprising at least a 2:1 molar ratio of glycine to serine.

Abstract: The present invention provides biomarkers for sensitive, specific, accurate and quantitative diagnosis and assessment of chronic hypoxia. In particular, the present invention provides 2-hydroxyglutarate as a biomarker that is differentially produced in chronic hypoxia. Furthermore, embodiments of the invention are able to differentiate between chronic and acute hypoxia. Assays for levels of 2-hydroxyglutarate may be used alone or in conjunction with additional biomarkers of hypoxia to increase the precision of analysis. In particular embodiments of the invention, the level of 2-hydroxyglutarate and at least one second biomarker may be assayed to generate a hypoxic profile that can be compared to a reference or control profile, thereby diagnosing a subject as normoxic, chronically hypoxic, or acutely hypoxic.

Abstract: Methods of treating individuals identified as having cancer using ATP citrate lyase inhibitor and/or tricarboxylate transporter inhibitor are disclosed. Methods of inducing apoptosis in cancer cells using an ATP citrate lyase inhibitor and/or tri-carboxylate transporter inhibitor are disclosed. of treating an individual who has cancer comprising the steps of identifying the cancer as having a high rate of aerobic glycolysis, and administering an ATP citrate lyase inhibitor and/or tricarboxylate transporter inhibitor are disclosed. Methods of treating individuals who have cancer using compounds that inhibit the expression of ATP citrate lyase or tricarboxylate transporter are disclosed. Methods of identifying a compound with anticancer activity are disclosed.