Abstract: Compositions comprising (i) lactate oxidase (LOX) and Catalase (CAT), preferably in a 1:1 molar ratio; or (ii) a fusion polypeptide comprising both LOX and CAT, e.g., LOXCAT, and methods of use thereof for reducing blood lactate levels, increasing blood pyruvate levels, and/or decreasing blood lactate/pyruvate ratio in a subject.

Abstract: Methods for the treatment of disorders associated with mitochondrial dysfunction, including rare, inborn errors of metabolism caused by genetic mutations; neurodegenerative disease; diabetes; and aging and age-associated decline. Generally, the methods include administering a therapeutically effective amount of one or more treatments that (i) induce hemoglobin “left-shifting” and/or (ii) induce anemia, as described herein, to a subject who is in need of, or who has been determined to be in need of, such treatment.

Abstract: Methods of promoting hypoxia or the hypoxia response for the treatment or prevention of mitochondrial dysfunction and oxidative stress disorders are described. Methods for screening for targets of mitochondrial dysfunction and oxidative stress disorders are also described.

Abstract: Methods of promoting hypoxia or the hypoxia response for the treatment or prevention of mitochondrial dysfunction and oxidative stress disorders are described. Methods for screening for targets of mitochondrial dysfunction and oxidative stress disorders are also described.

Abstract: Compositions comprising (i) lactate oxidase (LOX) and Catalase (CAT), preferably in a 1:1 molar ratio; or (ii) a fusion polypeptide comprising both LOX and CAT, e.g., LOXCAT, and methods of use thereof for reducing blood lactate levels, increasing blood pyruvate levels, and/or decreasing blood lactate/pyruvate ratio in a subject.

Abstract: Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

Abstract: Methods of promoting hypoxia or the hypoxia response for the treatment or prevention of mitochondrial dysfunction and oxidative stress disorders are described. Methods for screening for targets of mitochondrial dysfunction and oxidative stress disorders are also described.

Abstract: Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

Abstract: Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

Abstract: Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

Abstract: Methods of treatment, diagnosis, and determining prognosis of subjects with cancer, generally comprising determining levels of glycine metabolism or a mitochondrial 1-carbon (1-C) pathway enzyme, e.g., SHMT2, MTHFD1L, or MTHFD2, and optionally administering an antifolate or an agent that inhibits a mitochondrial 1-carbon (1-C) pathway enzyme, e.g., SHMT2 or MTHFD2.

Abstract: Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

Abstract: The present invention generally relates to fluidic droplets, and techniques for screening or sorting such fluidic droplets. In some embodiments, the fluidic droplets may contain cells (e.g., hybridoma cells) that can secrete various species, such as antibodies, for example. In one aspect, a plurality of fluidic droplets containing cells is screened to determine proteins, antibodies, polypeptides, peptides, nucleic acids, or the like. For example, cells able to secrete species such as antibodies may be selected according to certain embodiments of the invention. Examples of such cells include, for instance, immortal cells such as hybridomas, or non-immortal cells such as B-cells. For instance, blood cells may be encapsulated within a plurality of fluidic droplets, and the cells able to produce antibodies may be determined. In some cases, expression or secretion levels may be determined using signaling entities, for example, determinable microparticles present within the fluidic droplet.

Abstract: The invention, in some aspects, relates to methods for characterizing glucose-related metabolic disorders. In some aspects, the invention relates to methods and kits useful for diagnosing, classifying, profiling, and treating glucose-related metabolic disorders. In some aspects, the invention relates to methods useful for diagnosing, classifying, profiling, and treating diabetes.

Abstract: The present invention generally relates to fluidic droplets, and techniques for screening or sorting such fluidic droplets. In some embodiments, the fluidic droplets may contain cells (e.g., hybridoma cells) that can secrete various species, such as antibodies, for example. In one aspect, a plurality of fluidic droplets containing cells is screened to determine proteins, antibodies, polypeptides, peptides, nucleic acids, or the like. For example, cells able to secrete species such as antibodies may be selected according to certain embodiments of the invention. Examples of such cells include, for instance, immortal cells such as hybridomas, or non-immortal cells such as B-cells. For instance, blood cells may be encapsulated within a plurality of fluidic droplets, and the cells able to produce antibodies may be determined. In some cases, expression or secretion levels may be determined using signaling entities, for example, determinable microparticles present within the fluidic droplet.