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During lung infection, bloodstream neutrophils (PMNs) responding to infection travel to the airspace lumen. Although successful arrival of microbicidal PMNs to the airspace is essential for host defense against inhaled pathogens, excessive accumulation of PMNs in the lung contributes to the pathogenesis of several prevalent lung disorders, including acute lung injury, bronchiectasis, and COPD. Unfortunately, there is no treatment for controlling PMN accumulation in the lung.

This technology includes the development and use of small molecule activators of pyruvate kinase (PK) for the treatment of inherited nonspherocytic hemolytic anemia, including PK deficiency. PK deficiency is caused by an inherited deficiency in an enzyme that reduces the lifespan of red blood cells. More than 150 unique mutations have been identified in the PK gene that lead to decreased activity in this essential enzyme in the glycolytic pathway. The prematurely lysed red blood cells can lead to jaundice, splenomegaly, and a hemolytic anemia.

This technology includes the synthesis and use of novel PI3K and HDAC dual inhibitors for the treatment of several cancers. Phosphatidylinositol 3-kinase (PI3K) is activated in many human cancers, and inhibition of these kinases is an established cancer treatment. Histone deacetylases (HDACs) are key regulators of the cell cycle that function through regulating expression of tumor suppressors (p21 and p27), c-Myc and cyclin D1. HDAC inhibition is an emerging therapeutic approach for the treatment of several cancers.

This technology includes the identification and use of a combination therapy consisting of human recombinant N-acetylgalactosamine-6-sulfate sulfatase (hrGALNS) and the pharmacological chaperone compounds Ezetimibe and Pranlukast for the treatment of Mucopolysaccharidosis Type IVA (MPS IVA). MPS IVA is a rare disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Currently, hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are available for patients with MPS IVA.

This technology includes the use of the combination of the compounds Chroman-1 and Emricasan to achieve virtually 100% cell survival during human pluripotent stem cell passaging, cryopreservation/thawing, and differentiation in 2D and 3D cultures. Human pluripotent stem cells, including ESCs and iPSCs, are highly sensitive cells and undergo apoptosis during these routine procedures. A screening approach was used to identify the combination of the two compounds in this invention.

This technology includes the use of the small molecule metarrestin (ML246) for the treatment of several types of pancreatic cancer. A subcellular structure called the perinucleolar compartment (PNC) is frequently found in metastatic tumors and cancer stem cells. Reduction of PNC prevalence followed by medicinal chemistry was used to identify metarrestin as a compound that reduces PNC prevalence without significantly impacting cell viability. In vitro and in vivo animal work have demonstrated desirable pharmacokinetic properties as well as a reduction in metastatic burden and extended survival.

This technology includes the identification and use of small molecules to rescue cells undergoing ferroptosis, a type of programmed cell death. These small molecules can be used as treatments in situations where epithelial cells are being damaged, including respiratory disorders, brain injury (including traumatic brain injury), renal injury, radiation-induced injury, and neurodegenerative disorders. Ferroptosis is a type of programmed cell death that is triggered by an increased presence of oxidants.

This invention relates to two devices that reliably, sensitively, and accurately measures force during handgrip contraction and subsequent relaxation. A delayed relaxation after a sustained and forceful handgrip is a cardinal symptom of myotonic dystrophies (DM). This delayed relaxation, handgrip myotonia, may be a therapeutic response biomarker in clinical trials.

This technology includes the combination therapy of tyrosine kinase inhibitors (TKIs) and tigecycline as a potential new treatment for acute myeloid leukemia (AML). The existing treatments available for AML are not adequate; for patients older than 60, the prognosis is poor, with a two-year survival probability of less than 10%. Tigecycline is a glycylcycline antibiotic that induces cell death via inhibition of mitochondrial protein synthesis.

This technology includes methods for screening compounds and compositions useful for inhibiting or reducing platelet deposition, adhesion, and/or aggregation. The present invention further relates to methods of treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, abrupt closure following angioplasty or stent placement, thrombosis induced by peripheral vascular surgery, peripheral vascular disease or thrombotic disorders resulting from atrial fibrillation or inflammation.