Bladder Cancer Patient-Derived Organoids and Avatars for Personalized Cancer Discovery

Prediction of treatment response has attracted growing attention in cancer research to improve clinical outcomes via individualized treatment regimens. Patient-derived organoids and xenografts are novel preclinical model systems that recapitulate the genetic and phenotypic features of parental tumors for this purpose. Organoid culture has been successfully established in multiple cancers and used for assessment of drug and immunotherapy responses. Patient-derived…
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The authors report a new high-affinity aptamer that binds to the transferrin receptor, also called CD71. Aptamers are oligonucleotides that fold into tertiary structures and can bind with high affinity to targets such as proteins. CD71 is overexpressed in rapidly growing cells, including many malignant cells. They show that the aptamer can be used to remove circulating malignant cells in the blood, improving the safety of cell therapy manufacturing practices.  They also collaborate with a team of biochemists from City College of New York to understand how the aptamer binds to CD71.
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Breath of Fresh Air: Towards Unraveling the Molecular Underpinnings of Sleep Apnea

Obstructive sleep apnea (OSA) is an important risk factor for multiple diseases (1). 425 million adults aged 30 – 69 are estimated to have severe OSA, including 65 million in the most affected country China (2). Positive airway pressure, the primary treatment for OSA, has relatively low adherence (3), emphasizing a continued need for more personalized treatments. OSA and related…
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In rodent models of type 2 diabetes (T2D), central administration of fibroblast growth factor 1 (FGF1) normalizes elevated blood glucose levels in a manner that is sustained for weeks or months. Increased activity of NPY/AgRP neurons in the hypothalamic arcuate nucleus (ARC) is implicated in the pathogenesis of hyperglycemia in these animals, and the ARC is a key brain area…
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An In Vivo Model of Human Macrophages in Metastatic Melanoma

Despite recent therapeutic progress, advanced melanoma remains lethal for many patients. The composition of the immune tumor microenvironment (TME) has decisive impacts on therapy response and disease outcome, and high-dimensional analyses of patient samples reveal the heterogeneity of the immune TME. Macrophages infiltrate TMEs and generally associate with tumor progression, but the underlying mechanisms are incompletely understood. Because experimental systems…
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Read the Publication This week we profile a recent publication in Blood Advances from the laboratory of Dr. Carol Miao (pictured, front row, left) at UW, Seattle Children’s, and Fred Hutch. Can you provide a brief overview of your lab’s current research focus? My lab focuses on investigating potentially clinically translatable approaches for hemophilia treatment. The goal is to develop…
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Pancreatic ductal adenocarcinoma (PDAC) typically presents as metastatic disease at diagnosis and remains refractory to treatment. Next generation sequencing efforts have described the genomic landscape, classified molecular subtypes, and confirmed frequent alterations in major driver genes, with coexistent alterations in KRAS and TP53 correlating with the highest metastatic burden and poorest outcomes. However, translating this information to guide therapy remains…
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The authors' work contributes to a growing research body on mucosal tissue regulatory T cells (Tregs), demonstrating that the previously uncharacterized genitourinary tract (GU)-localized Treg population is phenotypically and functionally distinct from canonical counterparts and may perform location-specific duties. As they are localized in a barrier tissue where pathogens may enter the body, GU tract (and other mucosa-localized) Tregs have large implications for the design of vaccines for sexually transmitted infections: mucosal vaccines aim to elicit robust anti-STI responses in local immune cells, so it is important to consider how Tregs may influence vaccine-induced immune responses.
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The authors found that TOLLIP, a gene associated with TB susceptibility, influences dendritic cell maturation, cytokine responses to M. tuberculosis ligands, and T cell activation in human cohorts. Using mice lacking the TOLLIP gene, they found that lung-resident dendritic cells also develop deiminished maturation during M. tuberculosis infection irrespective of bacterial burden or lung microenvirontment. Further, these mice develop diminished M. tuberculosis-specific T cell responses after infection, which is a critical component of an effective immune response to TB. Moreover, mice lacking TOLLIP did not induce T cell responses to the current vaccine against TB, Bacille Calmette-Guerin. These data suggest that TOLLIP alters dendritic cell activity in ways that impaire adaptive immune responses to TB in both mice and humans, and that understanding how this protein works may provide insight into improved vaccines and treatments.
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The microRNAs are non-coding RNAs which post-transcriptionally regulate the expression of many eukaryotic genes, and whose dysregulation is a driver of human disease. Here we report the discovery of a very slow (0.1 s−1) conformational rearrangement at the Dicer cleavage site of pre-miR-21, which regulates the relative concentration of readily- and inefficiently-processed RNA structural states. We show that this dynamic switch is affected by…
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