Danielle Carter

Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma

Jason Yongsheng Chan,et al, The Journal of Clinical Investigation, 2020.
To molecularly characterize the rare and aggressive tumors known as angiosarcomas, Chan et al utilized a combination of transcriptomic immuno-oncology profiling with multiplex immunohistochemistry and immunofluorescence. HALO image analysis software was used for the quantification of PD-L1, CD68, CD8, FOXP3, CD15, and ERG. From these studies, three phenotypes of patients were identified according to etiology, anatomical origin, signaling pathways, and the tumor inflammation signature. These distinct biological phenotypes provide opportunity for future studies to improve prognosis and treatment of a rare and deadly disease.

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PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding

Alexander Jaisl, et al, Neuron, 2020
To advance the molecular understanding of obesity, Jais and colleagues set out to identify neuronal populations in mice that respond to being fed a calorie dense, highly palatable food. They identified prepronociceptin (PNOC)-expressing neurons in the hypothalamus that are activated upon acute high fat diet feeding and promote overconsumption. In this publication, HALO image analysis software was used for quantification of transgene expression in mouse neuronal tissue. Future studies on PNOC-expressing neurons may advance prevention and treatment of obesity and associated metabolic diseases.

PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding Read More »

An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer

Paula Voabil,et al, Nature Medicine, 2021.
Dr. Paula Voabil and colleagues used a patient derived tumor fragment platform to investigate immune responses immediately following PD-1 blockade. The Tissue Classifier Add-on and the Multiplex IHC module of HALO® were used in this publication to quantify immune biomarkers in the tumor and stroma, contributing to their conclusion that the ability of tumors to respond to PD-1 blockage correlates with the ability of intratumoral immune cells to be reactivated by the blockade.

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Transmission of tauopathy strains is independent of their isoform composition

Alexander Jaisl, et al, Neuron, 2020.
To advance the molecular understanding of obesity, Jais and colleagues set out to identify neuronal populations in mice that respond to being fed a calorie dense, highly palatable food. They identified prepronociceptin (PNOC)-expressing neurons in the hypothalamus that are activated upon acute high fat diet feeding and promote overconsumption. In this publication, HALO image analysis software was used for quantification of transgene expression in mouse neuronal tissue. Future studies on PNOC-expressing neurons may advance prevention and treatment of obesity and associated metabolic diseases.

Transmission of tauopathy strains is independent of their isoform composition Read More »

Mechanical regulation of glycolysis via cytoskeleton architecture

Jin Suk Park,et al, Nature, 2020.
Park and colleagues explored the question of how regulation of glycolysis responds to structural changes in tissue architecture and chose lung cells and tissue for their studies due to the regular mechanical stress experienced during respiration. In vitro studies demonstrated downregulation of glycolysis following a change in substrate via the degradation of the platelet isoform of the phosphofructokinase (PFKP) enzyme. In vitro studies also showed that oncogenic transformation changed the ability of PFKP expression to change in response to mechanical stress. The researchers corroborated this result with in vivo work by performing immunohistochemical assays on control and malignant tissue cores from bronchi of lung cancer patients. The HALO Tissue Classifier Add-on was used to classify epithelium, stroma, and tumor within the tissue cores and the Cytonuclear IHC module was used to quantify cytoplasmic PFKP staining in bronchial epithelium.

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Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions

Jules Russick, et al, Journal for ImmunoTherapy of Cancer, 2020.
Natural killer (NK) cells are known to have cytotoxic effector functions in tumor immunosurveillance. More recently, evidence of a second potentially inhibitory or regulatory role have emerged. Here, Russick et al compared expression patterns of NK cells inside tumors to nontumoral NK cells to understand their inhibitory functions in the context of the non-small cell lung carcinoma (NSCLC) tumor microenvironment (TME). These studies identified a novel and specific gene signature of NK cells dysregulation in NSCLC that suggests that the TME may induce suppressive NK cells. HALO image analysis software was leveraged to quantify CD8 expression of formalin fixed paraffin embedded NSCLC sections with CD8 immunohistochemistry and a hematoxylin counterstain. While the presence of CD8 was previously known to be associated with good clinical outcomes, Russick and colleagues uncovered a more complex relationship where patients with low CD8+ T cells and high NK cell density had good outcomes, and those with high CD8+ T cells and high NK cell density had poor outcomes.

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Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival

Sandeep K Singhal, et al, Communications Biology, 2021.
Singhal and colleagues apply quantitative automated image analysis to investigate the role of a transcriptional regulator, Kaiso, in a diverse cohort of breast cancer tumors. Specifically, they utilized the Highplex FL Module with the Tissue Microarray Module of HALO to characterize the tumor microenvironment in breast cancer TMA cores, including pan-cytokeratin, PD-L1, CD8, and CD68. They found that cytoplasmic Kaiso is associated with an immune-suppressed tumor microenvironment and found novel connections between Kaiso and autophagy-related proteins LC3A/B that are associated with breast cancer subtype and survival. The mechanism(s) by which Kaiso promotes tumor progression will require future investigation.

Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival Read More »

Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein

Chris McKinnon, et al, Acta Neuropathologica Communications, 2020.
In this study, McKinnon et al identify overexpression of α-synuclein leading to catalytic impairment of the 26S proteosome in defined regions of rat brains. Brain tissue was fixed following α-synuclein overexpression for immunofluorescence studies of dopaminergic neurons which were quantified by the HALO image analysis platform. Future research will focus on characterizing the relationship between proteasome impairment and neurodegeneration.

Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein Read More »

Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

Lisa H Tostanoski, et al, Nature Medicine, 2020.
In this study led by researchers at Harvard Medical School, they report the first demonstration of prevention of severe clinical disease in a hamster model of SARS-CoV-2 that were provided with a single immunization of the adenovirus serotype 26 (Ad26) vaccine. The Ad26 vaccine utilizes a stabilized spike protein of the SARS-CoV-2 and in the United States this vaccine is commonly known as the Johnson and Johnson vaccine. This study, published in print in November 2020 contributed to the scientific body of evidence in animal models that enabled clinical vaccine trials that in turn led to emergency use approvals in the United States, Canada, and other countries. Researchers leveraged the Multiplex IHC module of HALO for evaluation of the percentage of SAR-N protein positive cells and for Iba-1 quantification. The Area Quantification IHC module was used to determine the percentage of SARS-CoV-2 sense or anti-sense probe or Mx1 protein as a function of area. The Cytonuclear IHC module and Area Quantification IHC modules were used in detection of MPO+ or CD3+ cells expressed as a proportion of total alveolar tissue.

Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters Read More »

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