Cancer therapies are being considered for treating rare noncancerous diseases like pulmonary hypertension (PH), but effective computational screening is lacking. Via transcriptomic differential dependency analyses leveraging parallels between cancer and PH, we mapped a landscape of cancer drug functions dependent upon rewiring of PH gene clusters. Bromodomain and extra-terminal motif (BET) protein inhibitors were predicted to rely upon several gene clusters inclusive of galectin-8 (LGALS8).
View Article and Find Full Text PDFAntioxid Redox Signal
April 2021
Endothelial-to-mesenchymal transition (EndMT) is a process that encompasses extensive transcriptional reprogramming of activated endothelial cells leading to a shift toward mesenchymal cellular phenotypes and functional responses. Initially observed in the context of embryonic development, in the last few decades EndMT is increasingly recognized as a process that contributes to a variety of pathologies in the adult organism. Within the settings of cardiovascular biology, EndMT plays a role in various diseases, including atherosclerosis, heart valvular disease, cardiac fibrosis, and myocardial infarction.
View Article and Find Full Text PDFDespite numerous reports implicating NADPH oxidases (Nox) in the pathogenesis of many diseases, precise regulation of this family of professional reactive oxygen species (ROS) producers remains unclear. A unique member of this family, Nox1 oxidase, functions as either a canonical or hybrid system using Nox organizing subunit 1 (NoxO1) or p47(phox), respectively, the latter of which is functional in vascular smooth muscle cells (VSMC). In this manuscript, we identify critical requirement of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50; aka NHERF1) for Nox1 activation and downstream responses.
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