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

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.

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.

Association of COVID-19 inflammation with activation of the C5a–C5aR1 axis

Julien Carvelli, et al, Nature, 2020
Researchers aiming to block excessive lung inflammation in COVID-19 patients found upregulated immune checkpoint biomarkers in patients with a range of COVID-19 symptoms (from paucisymptomatic to acute respiratory distress syndrome). In addition, Carvelli et al found increased expression of C5a, an inflammatory mediator, in serum and the C5aR1 receptor on myeloid cells in COVID-19 patients, which are known to initiate inflammatory responses by recruiting neutrophils and monocytes to lungs. An in vitro neutrophil migration assay quantified with the CytoNuclear FL Module of HALO demonstrated that the clinical stage therapeutic monoclonal antibody, avdoralimab, effectively inhibited C5a-induced neutrophil migration. The authors propose use of avdoralimab to limit excessive lung inflammation associated with acute respiratory distress in COVID-19 patients.

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.