Bioactive Recombinant Human Oncostatin M for NMR-Based Screening in Drug Discovery

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM from E. coli for biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded 1H, 15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of 15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 μM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening

Embodied Discourses of Literacy in the Lives of Two Preservice Teachers

This study examines the emerging teacher literacy identities of Ian and A.J., two preservice teachers in a graduate teacher education program in the United States. Using a poststructural feminisms theoretical framework, the study illustrates the embodiment of literacy pedagogy discourses in relation to the literacy courses’ discourse of comprehensive literacy and the literacy biographical discourses of Ian and A.J. The results of this study indicate the need to deconstruct how the discourse of comprehensive literacy limits how we, as literacy teacher educators, position, hear and respond to our preservice teachers and suggests the need for differentiation in our teacher education literacy courses

Effect of Anthracycline and anti-PD-1 Antibody Combination Therapy on Murine Carcinoma

Cancer is the second leading cause of death in the United States, accounting for over 500,000 deaths per year. Doxorubicin (DOX) is one of the main chemotherapeutic drugs used to treat many forms of cancer, but its inherent cardiotoxicity can have devastating side-effects. GPX-150 and GPX-160 are DOX analogs that are similar to their widely used counterpart, but with a structure known to be much less cardiotoxic. In vitro data testing these analogs against a variety of cancer cell lines has shown promising results, with GPX 160 proving to be as cytotoxic as Doxorubicin. We are currently testing the ability of these drugs to block growth of CT-26 colon carcinoma tumors in Balb/c mice when given alone or in combination with an anti-PD-1 antibody therapeutic. In this way, we hope to show the synergistic effects of using chemotherapy and immunotherapy in the same treatment. By comparing tumor volumes and overall health between treatment groups over a 56 day trial, valuable information will be obtained on the efficacy of these chemotherapeutic drugs, and there synergistic implications with anti-PD-1 antibodies

Scientific foundations for an IUCN Red List of ecosystems

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