Microtubule Integrity Regulates Budding Yeast Ram Pathway Gene Expression

During mitosis, cells must spatiotemporally regulate gene expression programs to ensure accurate cellular division. Failures to properly regulate mitotic progression result in aneuploidy, a hallmark of cancer. Entry and exit from mitosis is largely controlled by waves of cyclin-dependent kinase (CDK) activity coupled to targeted protein degradation. The correct timing of CDK-based mitotic regulation is coordinated with the structure and…
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In Situ Tools for Chromatin Structural Epigenomics

Technological progress over the past 15 years has fueled an explosion in genome-wide chromatin profiling tools that take advantage of low-cost short-read sequencing technologies to map particular chromatin features. Here we survey the recent development of epigenomic tools that provide precise positions of chromatin proteins genome-wide in intact cells or nuclei. Some profiling tools are based on tethering Micrococcal Nuclease…
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Aptamer-Based Traceless Multiplexed Cell Isolation Systems

In both biomedical research and clinical cell therapy manufacturing, there is a need for cell isolation systems that recover purified cells in the absence of any selection agent. Reported traceless cell isolation methods using engineered antigen-binding fragments or aptamers have been limited to processing a single cell type at a time. There remains an unmet need for cell isolation processes…
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Herpes simplex virus (HSV) naturally infects skin and mucosal surfaces, causing lifelong recurrent disease worldwide, with no cure or vaccine. Biomimetic human tissue and organ platforms provide attractive alternatives over animal models to recapitulate human diseases. Combining prevascularization and microfluidic approaches, we present a vascularized, three-dimensional skin-on-chip that mimics human skin architecture and is competent to immune-cell and drug perfusion.…
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As one of the leading causes of global mortality, cancer has prompted extensive research and development to advance efficacious drug discovery, sustained drug delivery and improved sensitivity in diagnosis. Towards these applications, nanofibers synthesized by electrospinning have exhibited great clinical potential as a biomimetic tumor microenvironment model for drug screening, a controllable platform for localized, prolonged drug release for cancer…
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PIK3CA-related overgrowth spectrum (PROS) conditions of the head and neck are treatment challenges. Traditionally, these conditions require multiple invasive interventions, with incomplete malformation removal, disfigurement, and possible dysfunction. Use of the PI3K inhibitor alpelisib, previously shown to be effective in PROS, has not been reported in PIK3CA-associated head and neck lymphatic malformations (HNLMs) or facial infiltrating lipomatosis (FIL). We describe prospective…
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Preferentially Expressed Antigen in Melanoma (PRAME) , a cancer testes antigen provides an ideal target for immunotherapy in AML. We have shown expression of PRAME in a significant subset of childhood and adult AML and lack of expression in normal hematopoiesis. Although an intracellular antigen, we developed a novel approach to target PRAME using a CAR construct encoding a targeting…
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Functional implication of stromal heterogeneity in the prostate remains incompletely understood. Using lineage tracing and light-sheet imaging, we show that some fibroblast cells at the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective ablation of prostatic stromal cells, rapidly induces prostate epithelial turnover and dedifferentiation that are…
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TP53 mutation is the most frequent genetic event in head and neck squamous cell carcinoma (HNSCC), found in over 80% of patients with HPV-negative disease. As mutations in the TP53 gene are associated with worse outcomes in HNSCC, novel therapeutic approaches are needed for patients with TP53 mutated tumors. The National Cancer Institute (NCI) sponsored a Clinical Trials Planning Meeting…
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Upregulated PD-1 Signaling Antagonizes Glomerular Health in Aged Kidneys and Disease

With an aging population, kidney health becomes an important medical and socioeconomic factor. Kidney aging mechanisms are not well understood. We previously showed that podocytes isolated from aged mice exhibit increased expression of programmed cell death protein 1 (PD-1) surface receptor and its 2 ligands (PD-L1 and PD-L2). PDCD1 transcript increased with age in microdissected human glomeruli, which correlated with lower…
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