Danielle Guerrero

Approaches to Analyzing Skin Tissue using HALO and HALO AI

Area Quantification, Events, HALO, HALO AI, HALO Modules, Highplex FL, News, Past Webinars, Spatial Analysis, Webinars / , , , , ,

6 May 2021 | Application Scientist, Natasha Carmell, will discuss and demonstrate workflow approaches for analysing skin sections stained with H&E and immunofluorescence. Using HALO AI we will identify and segment the corneal layer, epidermis, dermis, cartilage, sebaceous glands and lesions in H&E murine auricular tissues, followed by the segmentation of carcinoma from melanoma in fluorescent multiplexed Melanoma tissue. This AI based tissue segmentation will then be combined with biomarker quantification to identify CD8, CD68 and PDL1 positive populations using Highplex FL.

Approaches to Analyzing Skin Tissue using HALO and HALO AI Read More »

CRISPR-Cas9 gene editing of hepatitis B virus in chronically infected humanized mice

HALO Link Publications, Publications

Daniel Stone,et al, Molecular Therapy Methods & Clinical Development, 2021
Hepatitis B leads to over 850,000 deaths annually due to complications from chronic infection including cirrhosis and hepatocellular carcinoma. While antiviral drugs successfully reduce viral loads in patients, a cure does not yet exist. This study out of the Jerome laboratory at the Fred Hutchinson Cancer Research Center performed in vivo gene editing utilizing a mouse model for chronic HBV infections and demonstrated a proof-of-concept of safe and effective gene editing of the genomic form responsible for replication and persistence. This study utilized the HALO Link image management platform in conjunction with image acquisition on a Leica Biosystems Aperio VERSA 200 slide scanner for their RNAscope studies of Cas9 and HBV.

CRISPR-Cas9 gene editing of hepatitis B virus in chronically infected humanized mice Read More »

Monomeric/dimeric forms of Fgf15/FGF19 show differential activity in hepatocyte proliferation and metabolic function

HALO Link Publications, Metabolism, Publications /

Courtney M. Williams et al, The FASEB Journal, 2021
Williams and colleagues at Regeneron Pharmaceuticals perform structure/function relationship studies on Fgf15 and FGF19 using site-directed mutagenesis and downstream functional assays in order to understand their distinct functions in a common pathway. Both molecules are therapeutic targets due to involvement in hepatocellular carcinoma and bile acid production. This publication identifies a single cysteine residue is identified that controls dimerization and hepatocyte proliferation. Understanding these molecular pathways may inform future studies on hepatocellular carcinoma while limiting toxicity and induction of hepatocyte proliferation. Immunohistochemistry images were quantified in HALO Link using the Cytonuclear IHC module.

Monomeric/dimeric forms of Fgf15/FGF19 show differential activity in hepatocyte proliferation and metabolic function Read More »

Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma

HALO Publications, Publications / ,

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.

Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma Read More »

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

HALO Publications, Publications

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

HALO Publications, Publications /

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.

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

Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers

HALO Publications, Immuno-Oncology, Publications /

Myriam Chalabi, et al, Nature Medicine, 2020.
Immunotherapy is known to be effective in late-stage, mismatch repair (MMR) deficient colorectal cancers but not in MMR proficient cancer. This study reports the early results from the NICHE clinical trial that is evaluating treatment of early stage, nonmetastatic preoperative colon cancer with a CTLA-4 inhibitor and a PD-1 inhibitor. Chalabi and colleagues report that the treatment was well tolerated and that a major pathological response was seen in 19/20 patients with MMR deficient tumors and 3/15 MMR proficient tumors. HALO image analysis software was used in this publication for analysis of T-cell biomarkers CD3, CD8, and FOXP3 on chromogenically stained tumor biopsies. First, image registration with HALO was performed of three serial tissue sections. Tissue sections were annotated manually, and quantification of DAB positivity was performed with the Multiplex IHC module and expressed as a function of tumor area. The authors conclude that immunotherapy shows promise to become the standard of care in a defined group of early-stage colon cancers.

Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers Read More »

Transmission of tauopathy strains is independent of their isoform composition

HALO Publications, Publications

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 »

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