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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 a robust and highly efficient protocol that differentiates induced pluripotent stem cells (iPSCs) exclusively into nociceptors (also called sensory neurons) under chemically defined conditions. The use of hPSCs, including hESCs and iPSCs, holds great promise for disease modeling, drug discovery, and cell therapy. However, efficient and highly reproducible protocols have not been developed for most cell types that are relevant and urgently needed for translational applications.

This technology includes a robust and highly efficient protocol that differentiates human pluripotent stem cells (hPSCs) exclusively into nociceptors (also called sensory neurons) under chemically defined conditions. The use of hPSCs, including hESCs and iPSCs, holds great promise for drug screening, disease modeling, toxicology, and regenerative medicine. However, efficient and highly reproducible protocols have not been developed for most cell types that are relevant and urgently needed for translational applications.

This technology includes a method for creating functional, brain region-specific neural spheroids that can be used for disease modeling and therapeutic testing of compounds for neurological diseases. The developed protocol uses somatic cells, including iPSC-derived neurons, as well as astrocytes using means such as 96- or 384-well ultra-low attachment round-bottom plates. Spheroids have been generated using this method that model brain regions such as the ventral tegmental area and prefrontal cortex, which are implicated in Parkinson’s and Alzheimer’s disease.

This technology includes the use of autophagy upregulators such as ML246/metarrestin to counteract the tolerance that can build up through the therapeutic use of cannabinoids. Long-term administration of cannabinoids rapidly introduces tolerance and physical dependence, limiting its medical use and may lead to addiction and withdrawal symptoms. Cannabinoids mediate their effect by binding to and activating the cannabinoid receptor 1 (CNR1/CB1). Chronic exposure leads to CNR1 being targeted for degradation through a process of autophagy.

There is an acute deficit in chemical synthesis with respect to benchtop tools that are specifically designed to address the capability and efficiency of certain key aspects of chemical synthesis, namely reaction preparation, product isolation, and solvent removal. Chemical research currently relies upon a variety of devices that function in a manner that is disconnected, as well as difficult to integrate and automate; collectively, these device challenges hinder the efficient isolation and purification of desired chemical synthesis products.

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 includes the generation and use of two polyclonal antibodies that specifically recognizes the phosphorylation site pThr707 of Neuroligin 4 and pThr739 of Neuroligin 1. A peptide of the site around the phosphorylation site was generated and injected into rabbits to create an immune response. Serum was collected from the rabbits that was then affinity purified. The specificity of the resulting polyclonal antibodies was then determined using biochemical techniques.

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 invention is a novel statistical method for automatically detecting lesions in cross-sectional brain magnetic resonance imaging (MRI) studies. OASIS uses multimodal MRI from one image acquisition session and produces voxel-level probability maps of the brain that quantifies the likelihood that each voxel is part of a lesion. Binary lesion segmentations are created from these probability maps using a validated population-level threshold. In this application, fluid attenuated inversion recovery (FLAIR), proton density (PD), T2-weighted, and Tl-weighted volumes were used.